AVAHO

Adjuvant radiotherapy after radical prostatectomy provided no meaningful benefit in patients with prostate cancer but increased the risk for urinary and bowel morbidity, compared with men followed with observation alone, according to the latest results from the phase 3 RADICALS-RT trial.

The new findings showed no difference in the rate of 10-year freedom from distant metastases or overall survival in patients who received adjuvant radiotherapy vs. those who underwent observation with salvage radiotherapy if their disease progressed and provided further confirmation of earlier results reported in The Lancet in 2020.

Observation with early salvage radiotherapy in cases of biochemical failure should be the standard of care, concluded study coauthor Noel Clarke, MBBS, who presented the results at the annual meeting of the European Society for Medical Oncology.

Invited discussant and session cochair Shahneed Sandhu, MBBS, said that the findings definitively confirm the value of observation with salvage radiotherapy over adjuvant radiotherapy in this patient population.

“The approach of early salvage radiotherapy spared morbidity [from] radiation in the vast majority of patients, and further bowel and bladder toxicity is reduced in the setting of salvage radiotherapy,” said Dr. Sandhu, an associate professor and consultant medical oncologist at Peter MacCallum Cancer Centre, Victoria, Australia.

The aim of the RADICALS-RT study was to clarify the optimal timing for radiotherapy after radical prostatectomy in men with prostate cancer, which previously had been uncertain.

In the study, 697 patients were randomly assigned to adjuvant radiotherapy and 699 to observation with salvage radiotherapy. Participants had undergone radical prostatectomy; had a postoperative prostate-specific antigen (PSA) level ≤ 0.2 ng/mL; and at least one risk factor for cancer relapse, including pathologic T-stage III or IV, Gleason score of 7-10, positive margins, or preoperative PSA ≥ 10 ng/mL.

Patients in the observation arm received salvage radiotherapy if they experienced two consecutive PSA increases ≥ 0.1 ng/mL or three consecutive rises.

Overall, the investigators found similar rates of 10-year freedom from distant metastases in both arms: 93% in the adjuvant radiotherapy group vs. 90% in the observation group (hazard ratio, 0.68; P = .095). The 10-year overall survival rates were similar as well: 88% in the adjuvant radiotherapy group and 87% in the observation group (HR, 0.98; P = .92).

However, self-reported urinary and fecal incontinence rates at 1 year were significantly higher in the adjuvant radiotherapy group vs. the observation group, 60% of whom had not received salvage radiotherapy at that time.

Secondary outcome measures, including biochemical progression-free survival and time to further hormone therapy, were also similar in the treatment and observation arms.

Overall, the trial results “support the use of early salvage radiotherapy for PSA failure after radical prostatectomy rather than early adjuvant intervention, “ concluded Dr. Clarke, a professor and consultant urologist at the Christie Hospital and Salford Royal Hospital, Manchester, England.

And when biochemical recurrence does occur, Dr. Sandhu noted that prostate-specific membrane antigen PET is increasingly used in practice to help “define the extent of disease” and “tailor radiation fields.”

Dr. Clarke reported serving on advisory boards for Janssen, Astellas, and Bayer. Dr. Sandhu reported receiving research grant support and/or serving as a consultant or adviser for Advanced Accelerator Application (a Novartis company), AstraZeneca, Merck Sharp and Dohme, Roche/Genentech, Amgen, Pfizer, Merck Serono, Bristol-Myers Squibb, Novartis, Janssen, and Sehnwa.

A version of this article first appeared on Medscape.com.

Adjuvant radiotherapy after radical prostatectomy provided no meaningful benefit in patients with prostate cancer but increased the risk for urinary and bowel morbidity, compared with men followed with observation alone, according to the latest results from the phase 3 RADICALS-RT trial.

The new findings showed no difference in the rate of 10-year freedom from distant metastases or overall survival in patients who received adjuvant radiotherapy vs. those who underwent observation with salvage radiotherapy if their disease progressed and provided further confirmation of earlier results reported in The Lancet in 2020.

Observation with early salvage radiotherapy in cases of biochemical failure should be the standard of care, concluded study coauthor Noel Clarke, MBBS, who presented the results at the annual meeting of the European Society for Medical Oncology.

Invited discussant and session cochair Shahneed Sandhu, MBBS, said that the findings definitively confirm the value of observation with salvage radiotherapy over adjuvant radiotherapy in this patient population.

“The approach of early salvage radiotherapy spared morbidity [from] radiation in the vast majority of patients, and further bowel and bladder toxicity is reduced in the setting of salvage radiotherapy,” said Dr. Sandhu, an associate professor and consultant medical oncologist at Peter MacCallum Cancer Centre, Victoria, Australia.

The aim of the RADICALS-RT study was to clarify the optimal timing for radiotherapy after radical prostatectomy in men with prostate cancer, which previously had been uncertain.

In the study, 697 patients were randomly assigned to adjuvant radiotherapy and 699 to observation with salvage radiotherapy. Participants had undergone radical prostatectomy; had a postoperative prostate-specific antigen (PSA) level ≤ 0.2 ng/mL; and at least one risk factor for cancer relapse, including pathologic T-stage III or IV, Gleason score of 7-10, positive margins, or preoperative PSA ≥ 10 ng/mL.

Patients in the observation arm received salvage radiotherapy if they experienced two consecutive PSA increases ≥ 0.1 ng/mL or three consecutive rises.

Overall, the investigators found similar rates of 10-year freedom from distant metastases in both arms: 93% in the adjuvant radiotherapy group vs. 90% in the observation group (hazard ratio, 0.68; P = .095). The 10-year overall survival rates were similar as well: 88% in the adjuvant radiotherapy group and 87% in the observation group (HR, 0.98; P = .92).

However, self-reported urinary and fecal incontinence rates at 1 year were significantly higher in the adjuvant radiotherapy group vs. the observation group, 60% of whom had not received salvage radiotherapy at that time.

Secondary outcome measures, including biochemical progression-free survival and time to further hormone therapy, were also similar in the treatment and observation arms.

Overall, the trial results “support the use of early salvage radiotherapy for PSA failure after radical prostatectomy rather than early adjuvant intervention, “ concluded Dr. Clarke, a professor and consultant urologist at the Christie Hospital and Salford Royal Hospital, Manchester, England.

And when biochemical recurrence does occur, Dr. Sandhu noted that prostate-specific membrane antigen PET is increasingly used in practice to help “define the extent of disease” and “tailor radiation fields.”

Dr. Clarke reported serving on advisory boards for Janssen, Astellas, and Bayer. Dr. Sandhu reported receiving research grant support and/or serving as a consultant or adviser for Advanced Accelerator Application (a Novartis company), AstraZeneca, Merck Sharp and Dohme, Roche/Genentech, Amgen, Pfizer, Merck Serono, Bristol-Myers Squibb, Novartis, Janssen, and Sehnwa.

A version of this article first appeared on Medscape.com.

Adjuvant radiotherapy after radical prostatectomy provided no meaningful benefit in patients with prostate cancer but increased the risk for urinary and bowel morbidity, compared with men followed with observation alone, according to the latest results from the phase 3 RADICALS-RT trial.

The new findings showed no difference in the rate of 10-year freedom from distant metastases or overall survival in patients who received adjuvant radiotherapy vs. those who underwent observation with salvage radiotherapy if their disease progressed and provided further confirmation of earlier results reported in The Lancet in 2020.

Observation with early salvage radiotherapy in cases of biochemical failure should be the standard of care, concluded study coauthor Noel Clarke, MBBS, who presented the results at the annual meeting of the European Society for Medical Oncology.

Invited discussant and session cochair Shahneed Sandhu, MBBS, said that the findings definitively confirm the value of observation with salvage radiotherapy over adjuvant radiotherapy in this patient population.

“The approach of early salvage radiotherapy spared morbidity [from] radiation in the vast majority of patients, and further bowel and bladder toxicity is reduced in the setting of salvage radiotherapy,” said Dr. Sandhu, an associate professor and consultant medical oncologist at Peter MacCallum Cancer Centre, Victoria, Australia.

The aim of the RADICALS-RT study was to clarify the optimal timing for radiotherapy after radical prostatectomy in men with prostate cancer, which previously had been uncertain.

In the study, 697 patients were randomly assigned to adjuvant radiotherapy and 699 to observation with salvage radiotherapy. Participants had undergone radical prostatectomy; had a postoperative prostate-specific antigen (PSA) level ≤ 0.2 ng/mL; and at least one risk factor for cancer relapse, including pathologic T-stage III or IV, Gleason score of 7-10, positive margins, or preoperative PSA ≥ 10 ng/mL.

Patients in the observation arm received salvage radiotherapy if they experienced two consecutive PSA increases ≥ 0.1 ng/mL or three consecutive rises.

Overall, the investigators found similar rates of 10-year freedom from distant metastases in both arms: 93% in the adjuvant radiotherapy group vs. 90% in the observation group (hazard ratio, 0.68; P = .095). The 10-year overall survival rates were similar as well: 88% in the adjuvant radiotherapy group and 87% in the observation group (HR, 0.98; P = .92).

However, self-reported urinary and fecal incontinence rates at 1 year were significantly higher in the adjuvant radiotherapy group vs. the observation group, 60% of whom had not received salvage radiotherapy at that time.

Secondary outcome measures, including biochemical progression-free survival and time to further hormone therapy, were also similar in the treatment and observation arms.

Overall, the trial results “support the use of early salvage radiotherapy for PSA failure after radical prostatectomy rather than early adjuvant intervention, “ concluded Dr. Clarke, a professor and consultant urologist at the Christie Hospital and Salford Royal Hospital, Manchester, England.

And when biochemical recurrence does occur, Dr. Sandhu noted that prostate-specific membrane antigen PET is increasingly used in practice to help “define the extent of disease” and “tailor radiation fields.”

Dr. Clarke reported serving on advisory boards for Janssen, Astellas, and Bayer. Dr. Sandhu reported receiving research grant support and/or serving as a consultant or adviser for Advanced Accelerator Application (a Novartis company), AstraZeneca, Merck Sharp and Dohme, Roche/Genentech, Amgen, Pfizer, Merck Serono, Bristol-Myers Squibb, Novartis, Janssen, and Sehnwa.

A version of this article first appeared on Medscape.com.

Despite the proven benefit of adding an immune checkpoint inhibitor (ICI) to preoperative chemotherapy for patients with triple-negative breast cancer (TNBC), the NeoTRIP Michelangelo trial stumbled at the finish line, showing that adding atezolizumab (Tecentriq) to nab-paclitaxel and carboplatin followed by surgery and adjuvant anthracycline-based chemotherapy did not improve 5-year event-free survival (EFS), compared with the same regimen without atezolizumab.

Although the trial did not produce the desired result, it still provided important impetus for researchers to do better, said lead investigator Luca Gianni, MD, chair of the international breast cancer research committee at Fondazione Michelangelo in Milan.

“I strongly believe that the results of NeoTRIP, rather than being viewed as negative, should bring forth the search for dependable and widely applicable predictors of ICIs’ benefit in women with operable triple negative breast cancer,” he said in an oral abstract session at the annual meeting of the European Society for Medical Oncology.

Other neoadjuvant trials with different agents have shown benefit from the addition of an ICI to chemotherapy for patients with TNBC, Dr. Gianni noted, with pembrolizumab (Keytruda) in Keynote-522, durvalumab (Imfinzi) in GeparNuevo, and with atezolizumab in IMpassion031.

NeoTRIP results

Dr. Gianni and colleagues had previously reported that adding atezolizumab to neoadjuvant carboplatin/nab-paclitaxel did not significantly improve pathologic complete response rates (pCR) in the randomized trial, although other trials of neoadjuvant ICIs in this population had shown a pCR benefit.

“Our analysis of NeoTRIP supports that pCR may not be an appropriate surrogate endpoint for the role of ICIs in early TNBC,” they wrote in that analysis.

At ESMO 2023, the investigators presented 5-year event-free survival rates, the primary study endpoint, and results of an exploratory analysis of predictive biomarkers.

In the phase 3 trial, patients with HER2-negative, estrogen receptor–negative, and progesterone receptor–negative early high-risk or locally advanced unilateral breast cancer were randomly assigned to receive eight cycles of carboplatin plus nab-paclitaxel with or without atezolizumab, followed by surgery and four cycles of an anthracycline-based chemotherapy regimen of the investigators choice.

A total of 280 patients were included in the intention-to-treat (ITT) population, including 138 assigned to receive atezolizumab and 142 who received chemotherapy alone.

Of these groups. 119 and 120, respectively, went on to surgery and were eligible for adjuvant chemotherapy. In all, 79 patients (66%) in the atezolizumab arm and 90 (75%) in the no-atezolizumab arm completed the four planned cycles of postoperative chemotherapy.

At a median follow-up of 54 months, the EFS rate with atezolizumab was 70.6%, compared with 74.9% without atezolizumab, translating into a nonsignificant hazard ratio of 1.076­­ for disease progression while on primary therapy or disease recurrence after surgery, or death from any cause, including unknown causes.

Pathologic complete responses key

In multivariate analysis, significant predictors for better EFS included achievement of a pCR; disease stage (early high risk vs. locally advanced); programmed death ligand-1 (PD-L1) levels above 1% as assessed by the SP142 assay; and higher levels of stromal tumor-infiltrating lymphocytes, but these factors were not predictive of atezolizumab benefit, Dr. Gianni said.

Among all patients who had a pCR, regardless of regimen, the 5-year EFS rate was 90.3%, compared with 55.7% for those who did not receive a pCR, translating into a hazard ratio of 0.19 for pathologic complete responses (P < .0001).

Looking at treatment-related adverse events occurring following surgery – that is, after atezolizumab therapy had stopped – they did not detect any new safety signals. The most common grade 3 or greater toxicity in each arm was neutropenia, followed by leukopenia, and in the atezolizumab arm there was one case of a grade 3 myocarditis that occurred 2 weeks after surgery and before the patient started on an anthracycline.

The authors also conducted a mass cytometry analysis of potential predictors of response to checkpoint inhibitors in TNBC, and reported the results in Nature.

“Basically, baseline density of several activated immune cells predicted for higher probability of pCR with atezolizumab but not with chemotherapy without atezolizumab,” Dr. Gianni said.

Specifically, they saw that high density of CD8-positive, TCF1-positive and Ki-67-positive markers were associated with increased pCR and EFS rates with the addition of atezolizumab.

Why no benefit to the ICI?

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University in Atlanta said that at least two possible explanations floated for the lack of either a pCR or EFS benefit in NeoTRIP don’t hold water.

For example, the theory that a difference in efficacy between PD-1 and PD-L1 inhibitors might explain the lack of benefit in NeoTRIP is undermined by IMpassion031, which showed pCR and EFS benefits with atezolizumab.

In addition, although NeoTRIP did not include an anthracycline in the neoadjuvant regimen, neither did the NeoPACT trial, in which patients received six cycles of neoadjuvant taxane, carboplatin, and pembrolizumab, and had a 58% pCR rate, with a high 2-year EFS rate among patients who had a pCR.

“As we know, triple-negative breast cancer is a heterogeneous disease. Could it be by chance that there are differences in tumor biology reflected across the various neoadjuvant trials, including molecular subtypes? Also in NeoTRIP, previously reported we’ve seen that there were a higher rate of TILs in the chemo-alone arm; high TILs can be associated with chemosensitivity, and maybe this influenced the results,” he said.

Predictive markers to immunotherapy in TNBC are still needed, he said, because neither PD-L1 expression, tumor mutational burden, or TILs have proven to be reliable biomarkers for this subtype.

The NeoTRIP Michelangelo trial was supported by Hoffman-La Roche and Celgene. Dr. Gianni disclosed financial interests with Roche and others including advisory board activity, consulting, and personal fees. Dr. Kalinsky reported advisory/consulting activities for various companies, including Genentech/Roche.

Despite the proven benefit of adding an immune checkpoint inhibitor (ICI) to preoperative chemotherapy for patients with triple-negative breast cancer (TNBC), the NeoTRIP Michelangelo trial stumbled at the finish line, showing that adding atezolizumab (Tecentriq) to nab-paclitaxel and carboplatin followed by surgery and adjuvant anthracycline-based chemotherapy did not improve 5-year event-free survival (EFS), compared with the same regimen without atezolizumab.

Although the trial did not produce the desired result, it still provided important impetus for researchers to do better, said lead investigator Luca Gianni, MD, chair of the international breast cancer research committee at Fondazione Michelangelo in Milan.

“I strongly believe that the results of NeoTRIP, rather than being viewed as negative, should bring forth the search for dependable and widely applicable predictors of ICIs’ benefit in women with operable triple negative breast cancer,” he said in an oral abstract session at the annual meeting of the European Society for Medical Oncology.

Other neoadjuvant trials with different agents have shown benefit from the addition of an ICI to chemotherapy for patients with TNBC, Dr. Gianni noted, with pembrolizumab (Keytruda) in Keynote-522, durvalumab (Imfinzi) in GeparNuevo, and with atezolizumab in IMpassion031.

NeoTRIP results

Dr. Gianni and colleagues had previously reported that adding atezolizumab to neoadjuvant carboplatin/nab-paclitaxel did not significantly improve pathologic complete response rates (pCR) in the randomized trial, although other trials of neoadjuvant ICIs in this population had shown a pCR benefit.

“Our analysis of NeoTRIP supports that pCR may not be an appropriate surrogate endpoint for the role of ICIs in early TNBC,” they wrote in that analysis.

At ESMO 2023, the investigators presented 5-year event-free survival rates, the primary study endpoint, and results of an exploratory analysis of predictive biomarkers.

In the phase 3 trial, patients with HER2-negative, estrogen receptor–negative, and progesterone receptor–negative early high-risk or locally advanced unilateral breast cancer were randomly assigned to receive eight cycles of carboplatin plus nab-paclitaxel with or without atezolizumab, followed by surgery and four cycles of an anthracycline-based chemotherapy regimen of the investigators choice.

A total of 280 patients were included in the intention-to-treat (ITT) population, including 138 assigned to receive atezolizumab and 142 who received chemotherapy alone.

Of these groups. 119 and 120, respectively, went on to surgery and were eligible for adjuvant chemotherapy. In all, 79 patients (66%) in the atezolizumab arm and 90 (75%) in the no-atezolizumab arm completed the four planned cycles of postoperative chemotherapy.

At a median follow-up of 54 months, the EFS rate with atezolizumab was 70.6%, compared with 74.9% without atezolizumab, translating into a nonsignificant hazard ratio of 1.076­­ for disease progression while on primary therapy or disease recurrence after surgery, or death from any cause, including unknown causes.

Pathologic complete responses key

In multivariate analysis, significant predictors for better EFS included achievement of a pCR; disease stage (early high risk vs. locally advanced); programmed death ligand-1 (PD-L1) levels above 1% as assessed by the SP142 assay; and higher levels of stromal tumor-infiltrating lymphocytes, but these factors were not predictive of atezolizumab benefit, Dr. Gianni said.

Among all patients who had a pCR, regardless of regimen, the 5-year EFS rate was 90.3%, compared with 55.7% for those who did not receive a pCR, translating into a hazard ratio of 0.19 for pathologic complete responses (P < .0001).

Looking at treatment-related adverse events occurring following surgery – that is, after atezolizumab therapy had stopped – they did not detect any new safety signals. The most common grade 3 or greater toxicity in each arm was neutropenia, followed by leukopenia, and in the atezolizumab arm there was one case of a grade 3 myocarditis that occurred 2 weeks after surgery and before the patient started on an anthracycline.

The authors also conducted a mass cytometry analysis of potential predictors of response to checkpoint inhibitors in TNBC, and reported the results in Nature.

“Basically, baseline density of several activated immune cells predicted for higher probability of pCR with atezolizumab but not with chemotherapy without atezolizumab,” Dr. Gianni said.

Specifically, they saw that high density of CD8-positive, TCF1-positive and Ki-67-positive markers were associated with increased pCR and EFS rates with the addition of atezolizumab.

Why no benefit to the ICI?

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University in Atlanta said that at least two possible explanations floated for the lack of either a pCR or EFS benefit in NeoTRIP don’t hold water.

For example, the theory that a difference in efficacy between PD-1 and PD-L1 inhibitors might explain the lack of benefit in NeoTRIP is undermined by IMpassion031, which showed pCR and EFS benefits with atezolizumab.

In addition, although NeoTRIP did not include an anthracycline in the neoadjuvant regimen, neither did the NeoPACT trial, in which patients received six cycles of neoadjuvant taxane, carboplatin, and pembrolizumab, and had a 58% pCR rate, with a high 2-year EFS rate among patients who had a pCR.

“As we know, triple-negative breast cancer is a heterogeneous disease. Could it be by chance that there are differences in tumor biology reflected across the various neoadjuvant trials, including molecular subtypes? Also in NeoTRIP, previously reported we’ve seen that there were a higher rate of TILs in the chemo-alone arm; high TILs can be associated with chemosensitivity, and maybe this influenced the results,” he said.

Predictive markers to immunotherapy in TNBC are still needed, he said, because neither PD-L1 expression, tumor mutational burden, or TILs have proven to be reliable biomarkers for this subtype.

The NeoTRIP Michelangelo trial was supported by Hoffman-La Roche and Celgene. Dr. Gianni disclosed financial interests with Roche and others including advisory board activity, consulting, and personal fees. Dr. Kalinsky reported advisory/consulting activities for various companies, including Genentech/Roche.

Despite the proven benefit of adding an immune checkpoint inhibitor (ICI) to preoperative chemotherapy for patients with triple-negative breast cancer (TNBC), the NeoTRIP Michelangelo trial stumbled at the finish line, showing that adding atezolizumab (Tecentriq) to nab-paclitaxel and carboplatin followed by surgery and adjuvant anthracycline-based chemotherapy did not improve 5-year event-free survival (EFS), compared with the same regimen without atezolizumab.

Although the trial did not produce the desired result, it still provided important impetus for researchers to do better, said lead investigator Luca Gianni, MD, chair of the international breast cancer research committee at Fondazione Michelangelo in Milan.

“I strongly believe that the results of NeoTRIP, rather than being viewed as negative, should bring forth the search for dependable and widely applicable predictors of ICIs’ benefit in women with operable triple negative breast cancer,” he said in an oral abstract session at the annual meeting of the European Society for Medical Oncology.

Other neoadjuvant trials with different agents have shown benefit from the addition of an ICI to chemotherapy for patients with TNBC, Dr. Gianni noted, with pembrolizumab (Keytruda) in Keynote-522, durvalumab (Imfinzi) in GeparNuevo, and with atezolizumab in IMpassion031.

NeoTRIP results

Dr. Gianni and colleagues had previously reported that adding atezolizumab to neoadjuvant carboplatin/nab-paclitaxel did not significantly improve pathologic complete response rates (pCR) in the randomized trial, although other trials of neoadjuvant ICIs in this population had shown a pCR benefit.

“Our analysis of NeoTRIP supports that pCR may not be an appropriate surrogate endpoint for the role of ICIs in early TNBC,” they wrote in that analysis.

At ESMO 2023, the investigators presented 5-year event-free survival rates, the primary study endpoint, and results of an exploratory analysis of predictive biomarkers.

In the phase 3 trial, patients with HER2-negative, estrogen receptor–negative, and progesterone receptor–negative early high-risk or locally advanced unilateral breast cancer were randomly assigned to receive eight cycles of carboplatin plus nab-paclitaxel with or without atezolizumab, followed by surgery and four cycles of an anthracycline-based chemotherapy regimen of the investigators choice.

A total of 280 patients were included in the intention-to-treat (ITT) population, including 138 assigned to receive atezolizumab and 142 who received chemotherapy alone.

Of these groups. 119 and 120, respectively, went on to surgery and were eligible for adjuvant chemotherapy. In all, 79 patients (66%) in the atezolizumab arm and 90 (75%) in the no-atezolizumab arm completed the four planned cycles of postoperative chemotherapy.

At a median follow-up of 54 months, the EFS rate with atezolizumab was 70.6%, compared with 74.9% without atezolizumab, translating into a nonsignificant hazard ratio of 1.076­­ for disease progression while on primary therapy or disease recurrence after surgery, or death from any cause, including unknown causes.

Pathologic complete responses key

In multivariate analysis, significant predictors for better EFS included achievement of a pCR; disease stage (early high risk vs. locally advanced); programmed death ligand-1 (PD-L1) levels above 1% as assessed by the SP142 assay; and higher levels of stromal tumor-infiltrating lymphocytes, but these factors were not predictive of atezolizumab benefit, Dr. Gianni said.

Among all patients who had a pCR, regardless of regimen, the 5-year EFS rate was 90.3%, compared with 55.7% for those who did not receive a pCR, translating into a hazard ratio of 0.19 for pathologic complete responses (P < .0001).

Looking at treatment-related adverse events occurring following surgery – that is, after atezolizumab therapy had stopped – they did not detect any new safety signals. The most common grade 3 or greater toxicity in each arm was neutropenia, followed by leukopenia, and in the atezolizumab arm there was one case of a grade 3 myocarditis that occurred 2 weeks after surgery and before the patient started on an anthracycline.

The authors also conducted a mass cytometry analysis of potential predictors of response to checkpoint inhibitors in TNBC, and reported the results in Nature.

“Basically, baseline density of several activated immune cells predicted for higher probability of pCR with atezolizumab but not with chemotherapy without atezolizumab,” Dr. Gianni said.

Specifically, they saw that high density of CD8-positive, TCF1-positive and Ki-67-positive markers were associated with increased pCR and EFS rates with the addition of atezolizumab.

Why no benefit to the ICI?

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University in Atlanta said that at least two possible explanations floated for the lack of either a pCR or EFS benefit in NeoTRIP don’t hold water.

For example, the theory that a difference in efficacy between PD-1 and PD-L1 inhibitors might explain the lack of benefit in NeoTRIP is undermined by IMpassion031, which showed pCR and EFS benefits with atezolizumab.

In addition, although NeoTRIP did not include an anthracycline in the neoadjuvant regimen, neither did the NeoPACT trial, in which patients received six cycles of neoadjuvant taxane, carboplatin, and pembrolizumab, and had a 58% pCR rate, with a high 2-year EFS rate among patients who had a pCR.

“As we know, triple-negative breast cancer is a heterogeneous disease. Could it be by chance that there are differences in tumor biology reflected across the various neoadjuvant trials, including molecular subtypes? Also in NeoTRIP, previously reported we’ve seen that there were a higher rate of TILs in the chemo-alone arm; high TILs can be associated with chemosensitivity, and maybe this influenced the results,” he said.

Predictive markers to immunotherapy in TNBC are still needed, he said, because neither PD-L1 expression, tumor mutational burden, or TILs have proven to be reliable biomarkers for this subtype.

The NeoTRIP Michelangelo trial was supported by Hoffman-La Roche and Celgene. Dr. Gianni disclosed financial interests with Roche and others including advisory board activity, consulting, and personal fees. Dr. Kalinsky reported advisory/consulting activities for various companies, including Genentech/Roche.

During treatment for metastatic cancer, remote monitoring of symptoms using electronic patient-reported outcomes (ePROs) reduced health care visits and improved patients’ physical function and quality of life, but did not impact overall survival, according to findings from the PRO-TECT trial.

“Although survival was not impacted in this trial, patients found the intervention to be valuable and experienced improved quality of life and decreased hospitalizations,” said Ethan Basch, MD, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Jiyoung Ahn, PhD, professor of population health at NYU Langone Health and associate director of population science, NYU Langone Perlmutter Cancer Center, both in New York, said this study “provides exciting scientific evidence” supporting real-time, remote monitoring of PROs. Dr. Ahn was not involved with the PRO-TECT trial.

Symptoms among patients with advanced cancer receiving treatment are “exceedingly common,” Dr. Basch explained, but “unfortunately, evidence demonstrates that we as clinicians miss up to 50% of our patients’ symptoms with potential serious downstream consequences.”

Remote monitoring with ePROs can help clinicians detect patients’ symptoms early so they can intervene early.

In the PRO-TECT cluster-randomized trial, 52 oncology practices in the United States were randomly assigned (1:1) to remote monitoring with ePRO surveys or usual care. The cohort included 1,191 patients with metastatic cancer – with 593 patients at PRO practices and 598 patients at control practices. Participating practices could enroll up to 50 patients with any type of metastatic cancer, except for indolent lymphoma or acute leukemia, who were receiving systemic treatment.

Patients in the ePRO practices completed weekly surveys either online or using an automated telephone system for up to 1 year. The survey included questions related to nine common symptoms, performance status, and falls.

For symptoms that are severe or worsening, a real-time alert goes to the care team through the electronic health record or by an email, Dr. Basch explained. Similarly, reports highlighting the longitudinal trajectory of symptoms can be generated at patient visits and reviewed by clinicians, which can bring “the patient and the care team closer together by elevating those issues that are particularly salient to the patient’s experience,” he noted.

Patients completed over 91% of the electronic symptom surveys. After 24 months, the team observed no significant difference in the primary outcome of overall survival – 42.0 months with ePRO vs. 43.5 months with usual care (hazard ratio, 0.99; P = .86).

Dr. Basch and colleagues did, however, observe a 6% reduction in emergency or hospital admissions in the ePRO group, compared with usual care. The ePRO group also had a significantly longer time to first emergency admission (HR, 0.84; P = .03) and a decreased average number of admissions per patient over 1 year (1.48 vs. 1.81; P = .006).

At multiple time points, the team also observed “clinically meaningful and statistically significant” benefits in physical functioning, symptom control, and health-related quality of life, Dr. Basch reported. More patients in the ePRO than the usual-care group experienced benefits in fatigue (odds ratio, 1.77; P < .001), anorexia (OR, 1.32; P = .03), nausea/vomiting (OR, 1.40; P = .01), and sleep (OR, 1.73; P < .001).

Patients’ impressions of the ePRO symptom monitoring system were also “overwhelmingly” positive, Dr. Basch said. Most found the questions relevant and easy to understand and felt that their care team used the information, which made patients feel more in control of their care.

Nurses generally had a favorable impression of the system, with the majority stating that the information was helpful for electronic health record documentation and that it improved discussions with their patients and improved their efficiency.

However, about one-quarter of the nurses expressed reluctance about continuing to use the system, citing the “added work of the ePROs, particularly alerts that were triggered that prompted them to call their patients, particularly during the pandemic when nurses in the United States were pulled in many directions,” Dr. Basch said.

He noted that future ePRO implementations should aim to integrate ePROs into care processes and adjust nurse responsibilities to allow time for ePRO work.

It will also be important to offer a variety of ePRO platforms that are easily accessible for different patient groups. “Notably,” said Dr. Basch, about one-third of the patients selected the automated telephone option. These were largely patients living in rural areas of the United States with lower socioeconomic status and lower health literacy, “suggesting that we need to think about our technologies to meet patients where they are,” he said.

Despite the positive outcomes, there are “challenges to widespread adoption,” agreed NYU’s Dr. Ahn.

These challenges include the need for physician adaptation to new technologies, data security, and ensuring patient engagement and compliance with remote monitoring systems.

“Successfully addressing these challenges is crucial for optimizing the integration of ePROs into cancer care,” Dr. Ahn said.

ESMO’s invited discussant, Anne Letsch, MD, noted that “cancer therapies are getting more complex, and it’s important that patients are well informed and empowered to get together with the treatment teams throughout therapy.”

The high completion rate with ePRO symptom surveys was “quite remarkable,” said Dr. Letsch, head of the Cancer Center at the University Hospital Schleswig Holstein, Kiel, Germany.

But, Dr. Letsch said, it’s “a pity” that there was no overall survival benefit among patients in the ePRO group. Perhaps overall survival is not what matters most in this context, she said. Instead, she asked, “are other outcomes, like health-related quality of life, symptom control and treatment safety, much more important?”

Dr. Basch also questioned whether the survival differences between the two groups may have been blunted because a substantial portion of the trial was conducted during the COVID-19 pandemic, when medical resources and treatments were delayed and diverted.

Dr. Basch pointed to a 2017 study he and colleagues conducted at a single tertiary care medical center, in which patients monitored with ePROs did demonstrate an overall survival benefit, compared with usual care.

Overall, though, the study demonstrated that “symptom monitoring with ePROs is feasible during routine treatment for advanced cancers across diverse practices in the U.S.” and improved patients’ quality of life, Dr. Basch said.

Funding for the study was provided by a grant from the Patient-Centered Outcomes Research Institute. Dr. Basch has disclosed relationships with Resilience Health, Sivan Health, Navigating Cancer, and AstraZeneca. Dr. Letsch and Dr. Ahn report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

During treatment for metastatic cancer, remote monitoring of symptoms using electronic patient-reported outcomes (ePROs) reduced health care visits and improved patients’ physical function and quality of life, but did not impact overall survival, according to findings from the PRO-TECT trial.

“Although survival was not impacted in this trial, patients found the intervention to be valuable and experienced improved quality of life and decreased hospitalizations,” said Ethan Basch, MD, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Jiyoung Ahn, PhD, professor of population health at NYU Langone Health and associate director of population science, NYU Langone Perlmutter Cancer Center, both in New York, said this study “provides exciting scientific evidence” supporting real-time, remote monitoring of PROs. Dr. Ahn was not involved with the PRO-TECT trial.

Symptoms among patients with advanced cancer receiving treatment are “exceedingly common,” Dr. Basch explained, but “unfortunately, evidence demonstrates that we as clinicians miss up to 50% of our patients’ symptoms with potential serious downstream consequences.”

Remote monitoring with ePROs can help clinicians detect patients’ symptoms early so they can intervene early.

In the PRO-TECT cluster-randomized trial, 52 oncology practices in the United States were randomly assigned (1:1) to remote monitoring with ePRO surveys or usual care. The cohort included 1,191 patients with metastatic cancer – with 593 patients at PRO practices and 598 patients at control practices. Participating practices could enroll up to 50 patients with any type of metastatic cancer, except for indolent lymphoma or acute leukemia, who were receiving systemic treatment.

Patients in the ePRO practices completed weekly surveys either online or using an automated telephone system for up to 1 year. The survey included questions related to nine common symptoms, performance status, and falls.

For symptoms that are severe or worsening, a real-time alert goes to the care team through the electronic health record or by an email, Dr. Basch explained. Similarly, reports highlighting the longitudinal trajectory of symptoms can be generated at patient visits and reviewed by clinicians, which can bring “the patient and the care team closer together by elevating those issues that are particularly salient to the patient’s experience,” he noted.

Patients completed over 91% of the electronic symptom surveys. After 24 months, the team observed no significant difference in the primary outcome of overall survival – 42.0 months with ePRO vs. 43.5 months with usual care (hazard ratio, 0.99; P = .86).

Dr. Basch and colleagues did, however, observe a 6% reduction in emergency or hospital admissions in the ePRO group, compared with usual care. The ePRO group also had a significantly longer time to first emergency admission (HR, 0.84; P = .03) and a decreased average number of admissions per patient over 1 year (1.48 vs. 1.81; P = .006).

At multiple time points, the team also observed “clinically meaningful and statistically significant” benefits in physical functioning, symptom control, and health-related quality of life, Dr. Basch reported. More patients in the ePRO than the usual-care group experienced benefits in fatigue (odds ratio, 1.77; P < .001), anorexia (OR, 1.32; P = .03), nausea/vomiting (OR, 1.40; P = .01), and sleep (OR, 1.73; P < .001).

Patients’ impressions of the ePRO symptom monitoring system were also “overwhelmingly” positive, Dr. Basch said. Most found the questions relevant and easy to understand and felt that their care team used the information, which made patients feel more in control of their care.

Nurses generally had a favorable impression of the system, with the majority stating that the information was helpful for electronic health record documentation and that it improved discussions with their patients and improved their efficiency.

However, about one-quarter of the nurses expressed reluctance about continuing to use the system, citing the “added work of the ePROs, particularly alerts that were triggered that prompted them to call their patients, particularly during the pandemic when nurses in the United States were pulled in many directions,” Dr. Basch said.

He noted that future ePRO implementations should aim to integrate ePROs into care processes and adjust nurse responsibilities to allow time for ePRO work.

It will also be important to offer a variety of ePRO platforms that are easily accessible for different patient groups. “Notably,” said Dr. Basch, about one-third of the patients selected the automated telephone option. These were largely patients living in rural areas of the United States with lower socioeconomic status and lower health literacy, “suggesting that we need to think about our technologies to meet patients where they are,” he said.

Despite the positive outcomes, there are “challenges to widespread adoption,” agreed NYU’s Dr. Ahn.

These challenges include the need for physician adaptation to new technologies, data security, and ensuring patient engagement and compliance with remote monitoring systems.

“Successfully addressing these challenges is crucial for optimizing the integration of ePROs into cancer care,” Dr. Ahn said.

ESMO’s invited discussant, Anne Letsch, MD, noted that “cancer therapies are getting more complex, and it’s important that patients are well informed and empowered to get together with the treatment teams throughout therapy.”

The high completion rate with ePRO symptom surveys was “quite remarkable,” said Dr. Letsch, head of the Cancer Center at the University Hospital Schleswig Holstein, Kiel, Germany.

But, Dr. Letsch said, it’s “a pity” that there was no overall survival benefit among patients in the ePRO group. Perhaps overall survival is not what matters most in this context, she said. Instead, she asked, “are other outcomes, like health-related quality of life, symptom control and treatment safety, much more important?”

Dr. Basch also questioned whether the survival differences between the two groups may have been blunted because a substantial portion of the trial was conducted during the COVID-19 pandemic, when medical resources and treatments were delayed and diverted.

Dr. Basch pointed to a 2017 study he and colleagues conducted at a single tertiary care medical center, in which patients monitored with ePROs did demonstrate an overall survival benefit, compared with usual care.

Overall, though, the study demonstrated that “symptom monitoring with ePROs is feasible during routine treatment for advanced cancers across diverse practices in the U.S.” and improved patients’ quality of life, Dr. Basch said.

Funding for the study was provided by a grant from the Patient-Centered Outcomes Research Institute. Dr. Basch has disclosed relationships with Resilience Health, Sivan Health, Navigating Cancer, and AstraZeneca. Dr. Letsch and Dr. Ahn report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

During treatment for metastatic cancer, remote monitoring of symptoms using electronic patient-reported outcomes (ePROs) reduced health care visits and improved patients’ physical function and quality of life, but did not impact overall survival, according to findings from the PRO-TECT trial.

“Although survival was not impacted in this trial, patients found the intervention to be valuable and experienced improved quality of life and decreased hospitalizations,” said Ethan Basch, MD, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Jiyoung Ahn, PhD, professor of population health at NYU Langone Health and associate director of population science, NYU Langone Perlmutter Cancer Center, both in New York, said this study “provides exciting scientific evidence” supporting real-time, remote monitoring of PROs. Dr. Ahn was not involved with the PRO-TECT trial.

Symptoms among patients with advanced cancer receiving treatment are “exceedingly common,” Dr. Basch explained, but “unfortunately, evidence demonstrates that we as clinicians miss up to 50% of our patients’ symptoms with potential serious downstream consequences.”

Remote monitoring with ePROs can help clinicians detect patients’ symptoms early so they can intervene early.

In the PRO-TECT cluster-randomized trial, 52 oncology practices in the United States were randomly assigned (1:1) to remote monitoring with ePRO surveys or usual care. The cohort included 1,191 patients with metastatic cancer – with 593 patients at PRO practices and 598 patients at control practices. Participating practices could enroll up to 50 patients with any type of metastatic cancer, except for indolent lymphoma or acute leukemia, who were receiving systemic treatment.

Patients in the ePRO practices completed weekly surveys either online or using an automated telephone system for up to 1 year. The survey included questions related to nine common symptoms, performance status, and falls.

For symptoms that are severe or worsening, a real-time alert goes to the care team through the electronic health record or by an email, Dr. Basch explained. Similarly, reports highlighting the longitudinal trajectory of symptoms can be generated at patient visits and reviewed by clinicians, which can bring “the patient and the care team closer together by elevating those issues that are particularly salient to the patient’s experience,” he noted.

Patients completed over 91% of the electronic symptom surveys. After 24 months, the team observed no significant difference in the primary outcome of overall survival – 42.0 months with ePRO vs. 43.5 months with usual care (hazard ratio, 0.99; P = .86).

Dr. Basch and colleagues did, however, observe a 6% reduction in emergency or hospital admissions in the ePRO group, compared with usual care. The ePRO group also had a significantly longer time to first emergency admission (HR, 0.84; P = .03) and a decreased average number of admissions per patient over 1 year (1.48 vs. 1.81; P = .006).

At multiple time points, the team also observed “clinically meaningful and statistically significant” benefits in physical functioning, symptom control, and health-related quality of life, Dr. Basch reported. More patients in the ePRO than the usual-care group experienced benefits in fatigue (odds ratio, 1.77; P < .001), anorexia (OR, 1.32; P = .03), nausea/vomiting (OR, 1.40; P = .01), and sleep (OR, 1.73; P < .001).

Patients’ impressions of the ePRO symptom monitoring system were also “overwhelmingly” positive, Dr. Basch said. Most found the questions relevant and easy to understand and felt that their care team used the information, which made patients feel more in control of their care.

Nurses generally had a favorable impression of the system, with the majority stating that the information was helpful for electronic health record documentation and that it improved discussions with their patients and improved their efficiency.

However, about one-quarter of the nurses expressed reluctance about continuing to use the system, citing the “added work of the ePROs, particularly alerts that were triggered that prompted them to call their patients, particularly during the pandemic when nurses in the United States were pulled in many directions,” Dr. Basch said.

He noted that future ePRO implementations should aim to integrate ePROs into care processes and adjust nurse responsibilities to allow time for ePRO work.

It will also be important to offer a variety of ePRO platforms that are easily accessible for different patient groups. “Notably,” said Dr. Basch, about one-third of the patients selected the automated telephone option. These were largely patients living in rural areas of the United States with lower socioeconomic status and lower health literacy, “suggesting that we need to think about our technologies to meet patients where they are,” he said.

Despite the positive outcomes, there are “challenges to widespread adoption,” agreed NYU’s Dr. Ahn.

These challenges include the need for physician adaptation to new technologies, data security, and ensuring patient engagement and compliance with remote monitoring systems.

“Successfully addressing these challenges is crucial for optimizing the integration of ePROs into cancer care,” Dr. Ahn said.

ESMO’s invited discussant, Anne Letsch, MD, noted that “cancer therapies are getting more complex, and it’s important that patients are well informed and empowered to get together with the treatment teams throughout therapy.”

The high completion rate with ePRO symptom surveys was “quite remarkable,” said Dr. Letsch, head of the Cancer Center at the University Hospital Schleswig Holstein, Kiel, Germany.

But, Dr. Letsch said, it’s “a pity” that there was no overall survival benefit among patients in the ePRO group. Perhaps overall survival is not what matters most in this context, she said. Instead, she asked, “are other outcomes, like health-related quality of life, symptom control and treatment safety, much more important?”

Dr. Basch also questioned whether the survival differences between the two groups may have been blunted because a substantial portion of the trial was conducted during the COVID-19 pandemic, when medical resources and treatments were delayed and diverted.

Dr. Basch pointed to a 2017 study he and colleagues conducted at a single tertiary care medical center, in which patients monitored with ePROs did demonstrate an overall survival benefit, compared with usual care.

Overall, though, the study demonstrated that “symptom monitoring with ePROs is feasible during routine treatment for advanced cancers across diverse practices in the U.S.” and improved patients’ quality of life, Dr. Basch said.

Funding for the study was provided by a grant from the Patient-Centered Outcomes Research Institute. Dr. Basch has disclosed relationships with Resilience Health, Sivan Health, Navigating Cancer, and AstraZeneca. Dr. Letsch and Dr. Ahn report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Short-term fasting during chemotherapy enhances health-related quality of life in patients with early breast cancer, with no untoward effects, according to late-breaking research presented on day 1 of the annual meeting of the European Society for Medical Oncology.

“Strikingly,” fasting also appeared to prevent fatigue, something patients with breast cancer struggle with, Daniela A. Koppold, MD, Charité University Medicine Berlin, noted in her oral presentation.

The study adds to other evidence suggesting that fasting around chemotherapy cycles may reduce toxicity and adverse effects associated with chemotherapy.

The invited discussant, Jann Arends, MD, with Freiburg (Germany) University Medical Center, said that the findings fit “very well” with previous observations. “Short-term fasting in subjects not at risk for malnutrition is feasible, well tolerated, and appears to improve several parameters of quality of life,” Dr. Arends said.
 

Promising supportive therapy

The randomized controlled trial assessed the feasibility and impact of short-term fasting on health-related quality of life, compared with a plant-based, low-sugar diet (active comparator) in 106 women with early breast cancer.

The chemotherapy regimens in the trial included four cycles of doxorubicin or epirubicin, followed by taxane therapy. The interventions for both groups occurred about 2 days before chemotherapy plus 24 hours after each cycle ended (about 60-72 hours total).

For the fasting group, this meant about 200 kcal/day through vegetable juices and vegetable broths. In between chemotherapy sessions, both groups were advised to eat a more vegetarian-focused diet, but that was not mandatory.

Health-related quality of life assessments occurred at baseline and after each chemotherapy session (cycle four at day 7) as well as after 4 and 6 months.

The investigators assessed health-related quality of life using the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) that measured the domains of physical, social/familial, emotional, and functional well-being.

At baseline, the two groups had similar FACT-G scores (fasting, 82.9 vs. plant diet, 81.9; P = .523). By day 7, the short-term–fasting group had a significantly better FACT-G score, compared with the plant-based–diet group (fasting, 78.3 vs. plant, 69.5; P = .021).

Although the two groups “started out from the same point, the fasting group had an incremental effect, which quite startled us,” Dr. Koppold told the audience. “Over the course of the chemotherapies, [fasting] had additive effects” and by cycle four of chemotherapy, the difference became statistically and clinically significant, indicating “much better” quality of life in the short-term–fasting group.

What was “even more striking,” said Dr. Koppold, was the impact fasting had on the secondary outcome of fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue).

“Short-term fasting not only had a protective effect on fatigue, compared to the control group, but the short-term–fasting group didn’t develop any clinically visible fatigue,” Dr. Koppold said. “They were in a normal range by cycle four while the control group developed fatigue as we would have expected.”

Importantly, she noted, fasting had no significant impact on weight. The study excluded women who were underweight or had a history of eating disorder or relevant psychopathology.

Summing up, Dr. Koppold said that short-term fasting represents a “promising” supportive therapy during breast cancer chemotherapy to enhance quality of life.

Commenting on the study, Rebecca Guterman, a registered dietitian at Perlmutter Cancer Center at NYU Langone Health, New York, said that it’s well known that a healthy diet plays “a key role during anticancer treatments.” Dietary changes can, for instance, help alleviate common chemotherapy side effects such as loss of appetite, nausea, fatigue, or diarrhea, she said.

These new findings support fasting for 60-72 hours around chemotherapy for some patients with breast cancer who may experience more rapid recovery and better quality of life, said Ms. Guterman.

However, she noted, the results should not be applied to patient populations outside of breast cancer or treatment regimens outside this study. And, she noted, “how the patient feels during the 60-72 hour fast also has to be considered.”

An individual’s “nutritional status must be considered. If a patient has poor appetite and loses weight between treatments, fasting should not be done before next treatment,” Ms. Guterman said.

The study was funded by a private sponsor (G. Müller, Munich, Germany) and a grant from the Günter and Regine KelmFoundation (Zurich). Dr. Koppold is a member of the steering board of ÄGHE e.V. (German-speaking Medical Association for Fasting and Nutrition); cofounder of the Academy for Integrative Fasting GbR; and consults for a mobile app on intermittent fasting (Fastic) as well as a company producing plant-based supplements (EVERYYIN). Dr. Arends has disclosed relationships with Baxter. Ms. Guterman has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Short-term fasting during chemotherapy enhances health-related quality of life in patients with early breast cancer, with no untoward effects, according to late-breaking research presented on day 1 of the annual meeting of the European Society for Medical Oncology.

“Strikingly,” fasting also appeared to prevent fatigue, something patients with breast cancer struggle with, Daniela A. Koppold, MD, Charité University Medicine Berlin, noted in her oral presentation.

The study adds to other evidence suggesting that fasting around chemotherapy cycles may reduce toxicity and adverse effects associated with chemotherapy.

The invited discussant, Jann Arends, MD, with Freiburg (Germany) University Medical Center, said that the findings fit “very well” with previous observations. “Short-term fasting in subjects not at risk for malnutrition is feasible, well tolerated, and appears to improve several parameters of quality of life,” Dr. Arends said.
 

Promising supportive therapy

The randomized controlled trial assessed the feasibility and impact of short-term fasting on health-related quality of life, compared with a plant-based, low-sugar diet (active comparator) in 106 women with early breast cancer.

The chemotherapy regimens in the trial included four cycles of doxorubicin or epirubicin, followed by taxane therapy. The interventions for both groups occurred about 2 days before chemotherapy plus 24 hours after each cycle ended (about 60-72 hours total).

For the fasting group, this meant about 200 kcal/day through vegetable juices and vegetable broths. In between chemotherapy sessions, both groups were advised to eat a more vegetarian-focused diet, but that was not mandatory.

Health-related quality of life assessments occurred at baseline and after each chemotherapy session (cycle four at day 7) as well as after 4 and 6 months.

The investigators assessed health-related quality of life using the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) that measured the domains of physical, social/familial, emotional, and functional well-being.

At baseline, the two groups had similar FACT-G scores (fasting, 82.9 vs. plant diet, 81.9; P = .523). By day 7, the short-term–fasting group had a significantly better FACT-G score, compared with the plant-based–diet group (fasting, 78.3 vs. plant, 69.5; P = .021).

Although the two groups “started out from the same point, the fasting group had an incremental effect, which quite startled us,” Dr. Koppold told the audience. “Over the course of the chemotherapies, [fasting] had additive effects” and by cycle four of chemotherapy, the difference became statistically and clinically significant, indicating “much better” quality of life in the short-term–fasting group.

What was “even more striking,” said Dr. Koppold, was the impact fasting had on the secondary outcome of fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue).

“Short-term fasting not only had a protective effect on fatigue, compared to the control group, but the short-term–fasting group didn’t develop any clinically visible fatigue,” Dr. Koppold said. “They were in a normal range by cycle four while the control group developed fatigue as we would have expected.”

Importantly, she noted, fasting had no significant impact on weight. The study excluded women who were underweight or had a history of eating disorder or relevant psychopathology.

Summing up, Dr. Koppold said that short-term fasting represents a “promising” supportive therapy during breast cancer chemotherapy to enhance quality of life.

Commenting on the study, Rebecca Guterman, a registered dietitian at Perlmutter Cancer Center at NYU Langone Health, New York, said that it’s well known that a healthy diet plays “a key role during anticancer treatments.” Dietary changes can, for instance, help alleviate common chemotherapy side effects such as loss of appetite, nausea, fatigue, or diarrhea, she said.

These new findings support fasting for 60-72 hours around chemotherapy for some patients with breast cancer who may experience more rapid recovery and better quality of life, said Ms. Guterman.

However, she noted, the results should not be applied to patient populations outside of breast cancer or treatment regimens outside this study. And, she noted, “how the patient feels during the 60-72 hour fast also has to be considered.”

An individual’s “nutritional status must be considered. If a patient has poor appetite and loses weight between treatments, fasting should not be done before next treatment,” Ms. Guterman said.

The study was funded by a private sponsor (G. Müller, Munich, Germany) and a grant from the Günter and Regine KelmFoundation (Zurich). Dr. Koppold is a member of the steering board of ÄGHE e.V. (German-speaking Medical Association for Fasting and Nutrition); cofounder of the Academy for Integrative Fasting GbR; and consults for a mobile app on intermittent fasting (Fastic) as well as a company producing plant-based supplements (EVERYYIN). Dr. Arends has disclosed relationships with Baxter. Ms. Guterman has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Short-term fasting during chemotherapy enhances health-related quality of life in patients with early breast cancer, with no untoward effects, according to late-breaking research presented on day 1 of the annual meeting of the European Society for Medical Oncology.

“Strikingly,” fasting also appeared to prevent fatigue, something patients with breast cancer struggle with, Daniela A. Koppold, MD, Charité University Medicine Berlin, noted in her oral presentation.

The study adds to other evidence suggesting that fasting around chemotherapy cycles may reduce toxicity and adverse effects associated with chemotherapy.

The invited discussant, Jann Arends, MD, with Freiburg (Germany) University Medical Center, said that the findings fit “very well” with previous observations. “Short-term fasting in subjects not at risk for malnutrition is feasible, well tolerated, and appears to improve several parameters of quality of life,” Dr. Arends said.
 

Promising supportive therapy

The randomized controlled trial assessed the feasibility and impact of short-term fasting on health-related quality of life, compared with a plant-based, low-sugar diet (active comparator) in 106 women with early breast cancer.

The chemotherapy regimens in the trial included four cycles of doxorubicin or epirubicin, followed by taxane therapy. The interventions for both groups occurred about 2 days before chemotherapy plus 24 hours after each cycle ended (about 60-72 hours total).

For the fasting group, this meant about 200 kcal/day through vegetable juices and vegetable broths. In between chemotherapy sessions, both groups were advised to eat a more vegetarian-focused diet, but that was not mandatory.

Health-related quality of life assessments occurred at baseline and after each chemotherapy session (cycle four at day 7) as well as after 4 and 6 months.

The investigators assessed health-related quality of life using the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) that measured the domains of physical, social/familial, emotional, and functional well-being.

At baseline, the two groups had similar FACT-G scores (fasting, 82.9 vs. plant diet, 81.9; P = .523). By day 7, the short-term–fasting group had a significantly better FACT-G score, compared with the plant-based–diet group (fasting, 78.3 vs. plant, 69.5; P = .021).

Although the two groups “started out from the same point, the fasting group had an incremental effect, which quite startled us,” Dr. Koppold told the audience. “Over the course of the chemotherapies, [fasting] had additive effects” and by cycle four of chemotherapy, the difference became statistically and clinically significant, indicating “much better” quality of life in the short-term–fasting group.

What was “even more striking,” said Dr. Koppold, was the impact fasting had on the secondary outcome of fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue).

“Short-term fasting not only had a protective effect on fatigue, compared to the control group, but the short-term–fasting group didn’t develop any clinically visible fatigue,” Dr. Koppold said. “They were in a normal range by cycle four while the control group developed fatigue as we would have expected.”

Importantly, she noted, fasting had no significant impact on weight. The study excluded women who were underweight or had a history of eating disorder or relevant psychopathology.

Summing up, Dr. Koppold said that short-term fasting represents a “promising” supportive therapy during breast cancer chemotherapy to enhance quality of life.

Commenting on the study, Rebecca Guterman, a registered dietitian at Perlmutter Cancer Center at NYU Langone Health, New York, said that it’s well known that a healthy diet plays “a key role during anticancer treatments.” Dietary changes can, for instance, help alleviate common chemotherapy side effects such as loss of appetite, nausea, fatigue, or diarrhea, she said.

These new findings support fasting for 60-72 hours around chemotherapy for some patients with breast cancer who may experience more rapid recovery and better quality of life, said Ms. Guterman.

However, she noted, the results should not be applied to patient populations outside of breast cancer or treatment regimens outside this study. And, she noted, “how the patient feels during the 60-72 hour fast also has to be considered.”

An individual’s “nutritional status must be considered. If a patient has poor appetite and loses weight between treatments, fasting should not be done before next treatment,” Ms. Guterman said.

The study was funded by a private sponsor (G. Müller, Munich, Germany) and a grant from the Günter and Regine KelmFoundation (Zurich). Dr. Koppold is a member of the steering board of ÄGHE e.V. (German-speaking Medical Association for Fasting and Nutrition); cofounder of the Academy for Integrative Fasting GbR; and consults for a mobile app on intermittent fasting (Fastic) as well as a company producing plant-based supplements (EVERYYIN). Dr. Arends has disclosed relationships with Baxter. Ms. Guterman has no relevant disclosures.

A version of this article first appeared on Medscape.com.

MADRID – More than one-third of patients with locally advanced esophageal cancer who have a complete clinical response to neoadjuvant chemoradiotherapy may be able to safely avoid major surgery, findings from the Dutch SANO trial suggest.

After 2 years, researchers found no significant differences in overall and disease-free survival between patients on active surveillance and those who received surgery either immediately following neoadjuvant chemoradiotherapy or who switched from active surveillance to surgery.

Overall, patients who underwent active surveillance had “noninferior overall survival at 2 years,” said Berend J. Van der Wilk, PhD candidate, Erasmus University, Rotterdam, the Netherlands, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Over the 2-year follow-up, at least 35% of patients on active surveillance were spared surgery. Patients on active surveillance who experienced locoregional regrowth could still undergo surgery, Mr. Van der Wilk said.

Magnus Nilsson, MD, PhD, the invited discussant, who was not involved in the research, said performing such a conceptually important and complex trial was a “huge achievement.” However, Dr. Nilsson highlighted some “major concerns” with the trial design, which could affect the generalizability of the findings.

Avoiding surgery?

Esophagectomy remains the “keystone of curative treatment for esophageal cancer,” Mr. Van der Wilks explained. However, this operation is a “major surgical procedure” that comes with a mortality rate of up to 5%. As many as 59% of patients experience complications.

The CROSS trial, which included more than 360 patients with esophageal or esophagogastric junction cancer, found that neoadjuvant chemoradiotherapy improved survival among patients with potentially curable disease; 29% of patients achieved a pathologic complete response.

Mr. Van der Wilk said those strong outcomes create some uncertainty as to whether all patients need standard surgery after chemoradiotherapy.

In other words, Mr. Van der Wilk asked, “Should we be willing to follow an active surveillance, organ-sparing strategy for patients with a clinical response?”

An active surveillance strategy, he said, would require frequent evaluations of the patient’s clinical response. Surgery would be performed only in cases of proven residual tumor in which there were no distant metastases. The potential pitfall of an active surveillance approach is that patients may develop unresectable tumor regrowths, “possibly resulting in inferior overall survival.”

To compare active surveillance with standard surgery, the team conducted a phase 3 noninferiority stepped-wedge cluster randomized trial involving patients with locally advanced esophageal cancer.

Patients received neoadjuvant chemoradiotherapy with carboplatin and paclitaxel for 5 weeks. Concurrent radiotherapy was delivered at 41.4 Gy in 23 fractions, 5 days per week, as in the CROSS trial.

More than 300 patients who achieved a complete clinical response 12 weeks after completing chemoradiotherapy were randomly assigned to undergo standard surgery or active surveillance. Surgery was performed for those with subsequent tumor regrowth.

Overall, 198 patients underwent active surveillance, and 111 patients underwent standard surgery. The two groups were well balanced in terms of median age, sex distribution, proportion of adenocarcinomas, and World Health Organization performance scores. At the last patient assessment, on July 6, 2023, the median follow-up was 38 months.

Overall, 101 of 111 patients in the standard surgery arm and 83 of 198 (42%) in the active surveillance group had surgery. The time to surgery in the active surveillance arm was 5.9 months, compared with 0.7 months with standard surgery. For both groups, the R0 resection rate was 98%.

Mr. Van der Wilk reported no significant difference in overall survival between the active surveillance and standard surgery groups (hazard ratio for death, 1.14; 95% confidence interval, 0.74-0.78; P = .55). Overall survival in the active surveillance group was noninferior to that in the standard surgery group at 2 years. Noninferiority was defined as an overall survival difference between the two arms of less than 15%.

Mr. Van der Wilk also reported no significant difference in disease-free survival between the active surveillance and the standard surgery groups – 35 months with active surveillance, and 49 months with surgery (HR, 1.35; P = .15). At 30 months following neoadjuvant chemoradiotherapy, 43% of patients on active surveillance and 34% with standard surgery developed distant metastases, but the difference was not significant (odds ratio, 1.45; P = .18).

Among the patients in the active surveillance arm who had a complete response, 35% (n = 69) had a persistent clinical response, while 17% (33 patients) developed distant metastases, and 48% (n = 96) experienced locoregional growth. The postoperative 90-day mortality was 4% in the active surveillance group and 5% in the surgery group.

Health-related quality of life was significantly better at 6 and 9 months in the active surveillance group, Mr. Van der Wilk noted.

Although Dr. Nilsson, the invited discussant, highlighted the importance of the trial, he also expressed concern over the trial design.

The intention-to-treat analysis was contaminated, Dr. Nilsson said, because the trial design allowed for one crossover, but patients in the trial crossed over at two time points – 35 patients who were initially assigned to standard surgery crossed over to the active surveillance arm, and later, seven patients from a preSANO trial were included in the active surveillance arm.

Dr. Nilsson also expressed concern about mixing squamous cell carcinoma and adenocarcinoma histologies in the study. If the authors had distinguished patients with squamous cell carcinoma and those with adenocarcinoma in each arm, there may have a difference in overall survival, given that squamous cell carcinoma is much easier to treat.

The study also included some patients who did not have a complete clinical response and whose surgery was delayed by more than 10 weeks – a practice that, Dr. Nilsson said, “does not really seem to be safe.” A recent study led by Dr. Nilsson found that delaying surgery for 10-12 weeks in comparison with 4-6 weeks did not improve histologic complete response or other pathologic endpoints and may have led to worse survival.

“I’m afraid it’s not really certain that it’s safe to prolong surgery more than 10 weeks or longer in the clinical noncomplete responders,” said Dr. Nilsson, from the department of clinical science, intervention, and technology, Karolinska Institute, Stockholm.

Overall, he said, the study “suggests that survival may be noninferior” among patients on active surveillance in comparison with those who undergo immediate surgery, but the findings need to be confirmed in a trial with a more stringent intention-to-treat analysis that is stratified by histologic subtypes.

The study was funded by the Dutch Cancer Society and the Netherlands Organisation for Health Research and Development (ZonMw). Mr. Van der Wilk has disclosed no relevant financial relationships. Dr. Nilsson has relationships with Medtronic, Intuitive Surgical, Bristol-Myers Squibb, and Merck Sharp & Dohme, from which he received no personal financial benefit.

A version of this article first appeared on Medscape.com.

MADRID – More than one-third of patients with locally advanced esophageal cancer who have a complete clinical response to neoadjuvant chemoradiotherapy may be able to safely avoid major surgery, findings from the Dutch SANO trial suggest.

After 2 years, researchers found no significant differences in overall and disease-free survival between patients on active surveillance and those who received surgery either immediately following neoadjuvant chemoradiotherapy or who switched from active surveillance to surgery.

Overall, patients who underwent active surveillance had “noninferior overall survival at 2 years,” said Berend J. Van der Wilk, PhD candidate, Erasmus University, Rotterdam, the Netherlands, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Over the 2-year follow-up, at least 35% of patients on active surveillance were spared surgery. Patients on active surveillance who experienced locoregional regrowth could still undergo surgery, Mr. Van der Wilk said.

Magnus Nilsson, MD, PhD, the invited discussant, who was not involved in the research, said performing such a conceptually important and complex trial was a “huge achievement.” However, Dr. Nilsson highlighted some “major concerns” with the trial design, which could affect the generalizability of the findings.

Avoiding surgery?

Esophagectomy remains the “keystone of curative treatment for esophageal cancer,” Mr. Van der Wilks explained. However, this operation is a “major surgical procedure” that comes with a mortality rate of up to 5%. As many as 59% of patients experience complications.

The CROSS trial, which included more than 360 patients with esophageal or esophagogastric junction cancer, found that neoadjuvant chemoradiotherapy improved survival among patients with potentially curable disease; 29% of patients achieved a pathologic complete response.

Mr. Van der Wilk said those strong outcomes create some uncertainty as to whether all patients need standard surgery after chemoradiotherapy.

In other words, Mr. Van der Wilk asked, “Should we be willing to follow an active surveillance, organ-sparing strategy for patients with a clinical response?”

An active surveillance strategy, he said, would require frequent evaluations of the patient’s clinical response. Surgery would be performed only in cases of proven residual tumor in which there were no distant metastases. The potential pitfall of an active surveillance approach is that patients may develop unresectable tumor regrowths, “possibly resulting in inferior overall survival.”

To compare active surveillance with standard surgery, the team conducted a phase 3 noninferiority stepped-wedge cluster randomized trial involving patients with locally advanced esophageal cancer.

Patients received neoadjuvant chemoradiotherapy with carboplatin and paclitaxel for 5 weeks. Concurrent radiotherapy was delivered at 41.4 Gy in 23 fractions, 5 days per week, as in the CROSS trial.

More than 300 patients who achieved a complete clinical response 12 weeks after completing chemoradiotherapy were randomly assigned to undergo standard surgery or active surveillance. Surgery was performed for those with subsequent tumor regrowth.

Overall, 198 patients underwent active surveillance, and 111 patients underwent standard surgery. The two groups were well balanced in terms of median age, sex distribution, proportion of adenocarcinomas, and World Health Organization performance scores. At the last patient assessment, on July 6, 2023, the median follow-up was 38 months.

Overall, 101 of 111 patients in the standard surgery arm and 83 of 198 (42%) in the active surveillance group had surgery. The time to surgery in the active surveillance arm was 5.9 months, compared with 0.7 months with standard surgery. For both groups, the R0 resection rate was 98%.

Mr. Van der Wilk reported no significant difference in overall survival between the active surveillance and standard surgery groups (hazard ratio for death, 1.14; 95% confidence interval, 0.74-0.78; P = .55). Overall survival in the active surveillance group was noninferior to that in the standard surgery group at 2 years. Noninferiority was defined as an overall survival difference between the two arms of less than 15%.

Mr. Van der Wilk also reported no significant difference in disease-free survival between the active surveillance and the standard surgery groups – 35 months with active surveillance, and 49 months with surgery (HR, 1.35; P = .15). At 30 months following neoadjuvant chemoradiotherapy, 43% of patients on active surveillance and 34% with standard surgery developed distant metastases, but the difference was not significant (odds ratio, 1.45; P = .18).

Among the patients in the active surveillance arm who had a complete response, 35% (n = 69) had a persistent clinical response, while 17% (33 patients) developed distant metastases, and 48% (n = 96) experienced locoregional growth. The postoperative 90-day mortality was 4% in the active surveillance group and 5% in the surgery group.

Health-related quality of life was significantly better at 6 and 9 months in the active surveillance group, Mr. Van der Wilk noted.

Although Dr. Nilsson, the invited discussant, highlighted the importance of the trial, he also expressed concern over the trial design.

The intention-to-treat analysis was contaminated, Dr. Nilsson said, because the trial design allowed for one crossover, but patients in the trial crossed over at two time points – 35 patients who were initially assigned to standard surgery crossed over to the active surveillance arm, and later, seven patients from a preSANO trial were included in the active surveillance arm.

Dr. Nilsson also expressed concern about mixing squamous cell carcinoma and adenocarcinoma histologies in the study. If the authors had distinguished patients with squamous cell carcinoma and those with adenocarcinoma in each arm, there may have a difference in overall survival, given that squamous cell carcinoma is much easier to treat.

The study also included some patients who did not have a complete clinical response and whose surgery was delayed by more than 10 weeks – a practice that, Dr. Nilsson said, “does not really seem to be safe.” A recent study led by Dr. Nilsson found that delaying surgery for 10-12 weeks in comparison with 4-6 weeks did not improve histologic complete response or other pathologic endpoints and may have led to worse survival.

“I’m afraid it’s not really certain that it’s safe to prolong surgery more than 10 weeks or longer in the clinical noncomplete responders,” said Dr. Nilsson, from the department of clinical science, intervention, and technology, Karolinska Institute, Stockholm.

Overall, he said, the study “suggests that survival may be noninferior” among patients on active surveillance in comparison with those who undergo immediate surgery, but the findings need to be confirmed in a trial with a more stringent intention-to-treat analysis that is stratified by histologic subtypes.

The study was funded by the Dutch Cancer Society and the Netherlands Organisation for Health Research and Development (ZonMw). Mr. Van der Wilk has disclosed no relevant financial relationships. Dr. Nilsson has relationships with Medtronic, Intuitive Surgical, Bristol-Myers Squibb, and Merck Sharp & Dohme, from which he received no personal financial benefit.

A version of this article first appeared on Medscape.com.

MADRID – More than one-third of patients with locally advanced esophageal cancer who have a complete clinical response to neoadjuvant chemoradiotherapy may be able to safely avoid major surgery, findings from the Dutch SANO trial suggest.

After 2 years, researchers found no significant differences in overall and disease-free survival between patients on active surveillance and those who received surgery either immediately following neoadjuvant chemoradiotherapy or who switched from active surveillance to surgery.

Overall, patients who underwent active surveillance had “noninferior overall survival at 2 years,” said Berend J. Van der Wilk, PhD candidate, Erasmus University, Rotterdam, the Netherlands, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Over the 2-year follow-up, at least 35% of patients on active surveillance were spared surgery. Patients on active surveillance who experienced locoregional regrowth could still undergo surgery, Mr. Van der Wilk said.

Magnus Nilsson, MD, PhD, the invited discussant, who was not involved in the research, said performing such a conceptually important and complex trial was a “huge achievement.” However, Dr. Nilsson highlighted some “major concerns” with the trial design, which could affect the generalizability of the findings.

Avoiding surgery?

Esophagectomy remains the “keystone of curative treatment for esophageal cancer,” Mr. Van der Wilks explained. However, this operation is a “major surgical procedure” that comes with a mortality rate of up to 5%. As many as 59% of patients experience complications.

The CROSS trial, which included more than 360 patients with esophageal or esophagogastric junction cancer, found that neoadjuvant chemoradiotherapy improved survival among patients with potentially curable disease; 29% of patients achieved a pathologic complete response.

Mr. Van der Wilk said those strong outcomes create some uncertainty as to whether all patients need standard surgery after chemoradiotherapy.

In other words, Mr. Van der Wilk asked, “Should we be willing to follow an active surveillance, organ-sparing strategy for patients with a clinical response?”

An active surveillance strategy, he said, would require frequent evaluations of the patient’s clinical response. Surgery would be performed only in cases of proven residual tumor in which there were no distant metastases. The potential pitfall of an active surveillance approach is that patients may develop unresectable tumor regrowths, “possibly resulting in inferior overall survival.”

To compare active surveillance with standard surgery, the team conducted a phase 3 noninferiority stepped-wedge cluster randomized trial involving patients with locally advanced esophageal cancer.

Patients received neoadjuvant chemoradiotherapy with carboplatin and paclitaxel for 5 weeks. Concurrent radiotherapy was delivered at 41.4 Gy in 23 fractions, 5 days per week, as in the CROSS trial.

More than 300 patients who achieved a complete clinical response 12 weeks after completing chemoradiotherapy were randomly assigned to undergo standard surgery or active surveillance. Surgery was performed for those with subsequent tumor regrowth.

Overall, 198 patients underwent active surveillance, and 111 patients underwent standard surgery. The two groups were well balanced in terms of median age, sex distribution, proportion of adenocarcinomas, and World Health Organization performance scores. At the last patient assessment, on July 6, 2023, the median follow-up was 38 months.

Overall, 101 of 111 patients in the standard surgery arm and 83 of 198 (42%) in the active surveillance group had surgery. The time to surgery in the active surveillance arm was 5.9 months, compared with 0.7 months with standard surgery. For both groups, the R0 resection rate was 98%.

Mr. Van der Wilk reported no significant difference in overall survival between the active surveillance and standard surgery groups (hazard ratio for death, 1.14; 95% confidence interval, 0.74-0.78; P = .55). Overall survival in the active surveillance group was noninferior to that in the standard surgery group at 2 years. Noninferiority was defined as an overall survival difference between the two arms of less than 15%.

Mr. Van der Wilk also reported no significant difference in disease-free survival between the active surveillance and the standard surgery groups – 35 months with active surveillance, and 49 months with surgery (HR, 1.35; P = .15). At 30 months following neoadjuvant chemoradiotherapy, 43% of patients on active surveillance and 34% with standard surgery developed distant metastases, but the difference was not significant (odds ratio, 1.45; P = .18).

Among the patients in the active surveillance arm who had a complete response, 35% (n = 69) had a persistent clinical response, while 17% (33 patients) developed distant metastases, and 48% (n = 96) experienced locoregional growth. The postoperative 90-day mortality was 4% in the active surveillance group and 5% in the surgery group.

Health-related quality of life was significantly better at 6 and 9 months in the active surveillance group, Mr. Van der Wilk noted.

Although Dr. Nilsson, the invited discussant, highlighted the importance of the trial, he also expressed concern over the trial design.

The intention-to-treat analysis was contaminated, Dr. Nilsson said, because the trial design allowed for one crossover, but patients in the trial crossed over at two time points – 35 patients who were initially assigned to standard surgery crossed over to the active surveillance arm, and later, seven patients from a preSANO trial were included in the active surveillance arm.

Dr. Nilsson also expressed concern about mixing squamous cell carcinoma and adenocarcinoma histologies in the study. If the authors had distinguished patients with squamous cell carcinoma and those with adenocarcinoma in each arm, there may have a difference in overall survival, given that squamous cell carcinoma is much easier to treat.

The study also included some patients who did not have a complete clinical response and whose surgery was delayed by more than 10 weeks – a practice that, Dr. Nilsson said, “does not really seem to be safe.” A recent study led by Dr. Nilsson found that delaying surgery for 10-12 weeks in comparison with 4-6 weeks did not improve histologic complete response or other pathologic endpoints and may have led to worse survival.

“I’m afraid it’s not really certain that it’s safe to prolong surgery more than 10 weeks or longer in the clinical noncomplete responders,” said Dr. Nilsson, from the department of clinical science, intervention, and technology, Karolinska Institute, Stockholm.

Overall, he said, the study “suggests that survival may be noninferior” among patients on active surveillance in comparison with those who undergo immediate surgery, but the findings need to be confirmed in a trial with a more stringent intention-to-treat analysis that is stratified by histologic subtypes.

The study was funded by the Dutch Cancer Society and the Netherlands Organisation for Health Research and Development (ZonMw). Mr. Van der Wilk has disclosed no relevant financial relationships. Dr. Nilsson has relationships with Medtronic, Intuitive Surgical, Bristol-Myers Squibb, and Merck Sharp & Dohme, from which he received no personal financial benefit.

A version of this article first appeared on Medscape.com.

MADRID – Five years on, the addition of the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy for women with high-risk hormone receptor–positive, HER2-negative (HR+/HER2–) early breast cancer continues to show modest but clinically significant benefits, compared with endocrine therapy alone.

Results of a planned 5-year efficacy analysis of the monarchE trial showed that at a median follow-up of 4.5 years, the abemaciclib/endocrine therapy combination was associated with a 7.6% absolute improvement in invasive disease–free survival (IDFS) and 6.7% edge in distant relapse–free survival (DRFS), compared with endocrine therapy alone, reported Nadia Harbeck, MD, from the Breast Center at Ludwig Maximilians University Hospital in Munich.

“The data are consistent with a carryover effect and further support the addition of adjuvant abemaciclib to endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive high-risk early breast cancer,” she said at the 2023 European Society for Medical Oncology Congress.
 

High recurrence risk

Although HR+/HER2– breast cancer, the most common subtype of breast cancer, is generally associated with better outcomes than other subtypes, patients with node-positive early disease are at high risk for early recurrence and need treatment intensification, Dr. Harbeck said.

The monarchE trial included two cohorts: a primary cohort consisting of patients deemed at high risk based on clinical pathological features such as the number of involved axillary nodes, grade 3 disease, and tumors 5 cm or larger, and a second cohort of patients with lower disease grade and smaller tumors but with high levels of the proliferation marker Ki-67.

A total of 5,637 patients were randomized to receive either 2 years of abemaciclib 150 mg twice daily plus endocrine therapy, or endocrine therapy alone, followed by 3-8 years of additional endocrine as clinically indicated in each study arm.

An earlier preplanned interim analysis of the phase 3 trial of more than 5,600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.

As that analysis showed, at a median follow-up of 15.5 months abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of IDFS vs. endocrine therapy alone.

At the time, the findings were hailed as practice-changing and, once approved for high-risk HR+/HER2-negative early breast cancer, as the new standard of care.

In the current analysis, Dr. Harbeck and colleagues looked at 5-year outcomes from a prespecified analysis, with a data cutoff of July 3, 2023.

All patients originally assigned to abemaciclib are now off the drug, and more than 80% have been followed for a minimum of 2 year since completing therapy with the CDK4/6 inhibitor.
 

Results

At 5 years there were cumulative totals of 407 IDFS events in the combination arm, compared with 585 in the endocrine therapy alone arm, a difference that translated into a hazard ratio of 0.68 favoring abemaciclib (P < .001).

The IDFS benefit with the combination was consistent across most subgroups, including older patients, perimenopausal and postmenopausal patients, those who had received prior neoadjuvant or adjuvant chemotherapy, all tumor sizes, number of positive lymph nodes, less favorable tumor stage or grade, and order of endocrine therapy (tamoxifen or aromatase inhibitor as first drug).

As noted before, DRFS, a secondary endpoint, also favored abemaciclib, with 345 events occurring over 5 years in the combination arm, compared with 501 in the endocrine therapy arm alone. This translated into a HR with the combination of 0.68 (P < .001).

There were fewer deaths in the abemaciclib arm (208 vs. 234), but this difference was not statistically significant.

The proportions of patients with treatment-emergent adverse events and serious adverse events (SAEs) were higher in the combination arm than in the endocrine therapy alone arm in all previous analyses of the trial data.

In the current analysis, “I would say it’s reassuring to see that the SAEs reported in the follow-up period, after the study treatment had been completed, are quite similar between the endocrine therapy alone arm and the abemaciclib plus endocrine therapy arm,” Dr. Harbeck said.
 

Changing road map

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University, Atlanta, commented that CDK4/6 inhibitors “have changed the road map for treating hormone receptor–positive, HER2-negative disease.”

To put the monarchE results in context, he compared them with those of the NATALEE trial, in which patients were randomized to endocrine therapy with or without the CDK4/6 inhibitor ribociclib (Kisqali). That combination was previously shown to provide a significant survival advantage for women with metastatic breast cancer.

In NATALEE, which included both high-risk and intermediate-risk patients with early breast cancer, the absolute difference in 3-year IDFS rates between the combination group and endocrine monotherapy groups was 3.3%.

To determine the ultimate value of combining a CDK4/6 inhibitor with endocrine therapy in early breast cancer, longer follow-up of both trials will be necessary, Dr. Kalinsky said.

“The reason that follow-up is critical for both of these studies is that for this subtype of breast cancer, based upon data including from the Early Breast Cancer Trialists Group, we can see approximately 50% of recurrences after the first 5 years, and we think of cytotoxic chemotherapy as benefiting patients within those first 5 years. And while we think of CDK4/6 inhibitors as being cytostatic drugs, we are seeing a carryover effect in which 2 years of abemaciclib is improving outcome at the 5-year landmark,” he said.

Questions that still need to be answered include the optimal duration of CDK4/6 inhibitor therapy, whether adjuvant therapy should be resumed when there are signs of renewed proliferation, and whether there would be a benefit to restarting CDK4/6 inhibitors when metastasis occurs.

The monarchE trial was sponsored by Eli Lilly and Co. Dr. Harbeck disclosed research funding and speaker’s bureau activity for Lilly and others, and a consulting or advisory role with Gilead, Roche, Sanofi, Sandoz, and Seagen. Dr. Kalinsky disclosed a consulting or advisory role with multiple companies, not including Lilly.

MADRID – Five years on, the addition of the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy for women with high-risk hormone receptor–positive, HER2-negative (HR+/HER2–) early breast cancer continues to show modest but clinically significant benefits, compared with endocrine therapy alone.

Results of a planned 5-year efficacy analysis of the monarchE trial showed that at a median follow-up of 4.5 years, the abemaciclib/endocrine therapy combination was associated with a 7.6% absolute improvement in invasive disease–free survival (IDFS) and 6.7% edge in distant relapse–free survival (DRFS), compared with endocrine therapy alone, reported Nadia Harbeck, MD, from the Breast Center at Ludwig Maximilians University Hospital in Munich.

“The data are consistent with a carryover effect and further support the addition of adjuvant abemaciclib to endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive high-risk early breast cancer,” she said at the 2023 European Society for Medical Oncology Congress.
 

High recurrence risk

Although HR+/HER2– breast cancer, the most common subtype of breast cancer, is generally associated with better outcomes than other subtypes, patients with node-positive early disease are at high risk for early recurrence and need treatment intensification, Dr. Harbeck said.

The monarchE trial included two cohorts: a primary cohort consisting of patients deemed at high risk based on clinical pathological features such as the number of involved axillary nodes, grade 3 disease, and tumors 5 cm or larger, and a second cohort of patients with lower disease grade and smaller tumors but with high levels of the proliferation marker Ki-67.

A total of 5,637 patients were randomized to receive either 2 years of abemaciclib 150 mg twice daily plus endocrine therapy, or endocrine therapy alone, followed by 3-8 years of additional endocrine as clinically indicated in each study arm.

An earlier preplanned interim analysis of the phase 3 trial of more than 5,600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.

As that analysis showed, at a median follow-up of 15.5 months abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of IDFS vs. endocrine therapy alone.

At the time, the findings were hailed as practice-changing and, once approved for high-risk HR+/HER2-negative early breast cancer, as the new standard of care.

In the current analysis, Dr. Harbeck and colleagues looked at 5-year outcomes from a prespecified analysis, with a data cutoff of July 3, 2023.

All patients originally assigned to abemaciclib are now off the drug, and more than 80% have been followed for a minimum of 2 year since completing therapy with the CDK4/6 inhibitor.
 

Results

At 5 years there were cumulative totals of 407 IDFS events in the combination arm, compared with 585 in the endocrine therapy alone arm, a difference that translated into a hazard ratio of 0.68 favoring abemaciclib (P < .001).

The IDFS benefit with the combination was consistent across most subgroups, including older patients, perimenopausal and postmenopausal patients, those who had received prior neoadjuvant or adjuvant chemotherapy, all tumor sizes, number of positive lymph nodes, less favorable tumor stage or grade, and order of endocrine therapy (tamoxifen or aromatase inhibitor as first drug).

As noted before, DRFS, a secondary endpoint, also favored abemaciclib, with 345 events occurring over 5 years in the combination arm, compared with 501 in the endocrine therapy arm alone. This translated into a HR with the combination of 0.68 (P < .001).

There were fewer deaths in the abemaciclib arm (208 vs. 234), but this difference was not statistically significant.

The proportions of patients with treatment-emergent adverse events and serious adverse events (SAEs) were higher in the combination arm than in the endocrine therapy alone arm in all previous analyses of the trial data.

In the current analysis, “I would say it’s reassuring to see that the SAEs reported in the follow-up period, after the study treatment had been completed, are quite similar between the endocrine therapy alone arm and the abemaciclib plus endocrine therapy arm,” Dr. Harbeck said.
 

Changing road map

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University, Atlanta, commented that CDK4/6 inhibitors “have changed the road map for treating hormone receptor–positive, HER2-negative disease.”

To put the monarchE results in context, he compared them with those of the NATALEE trial, in which patients were randomized to endocrine therapy with or without the CDK4/6 inhibitor ribociclib (Kisqali). That combination was previously shown to provide a significant survival advantage for women with metastatic breast cancer.

In NATALEE, which included both high-risk and intermediate-risk patients with early breast cancer, the absolute difference in 3-year IDFS rates between the combination group and endocrine monotherapy groups was 3.3%.

To determine the ultimate value of combining a CDK4/6 inhibitor with endocrine therapy in early breast cancer, longer follow-up of both trials will be necessary, Dr. Kalinsky said.

“The reason that follow-up is critical for both of these studies is that for this subtype of breast cancer, based upon data including from the Early Breast Cancer Trialists Group, we can see approximately 50% of recurrences after the first 5 years, and we think of cytotoxic chemotherapy as benefiting patients within those first 5 years. And while we think of CDK4/6 inhibitors as being cytostatic drugs, we are seeing a carryover effect in which 2 years of abemaciclib is improving outcome at the 5-year landmark,” he said.

Questions that still need to be answered include the optimal duration of CDK4/6 inhibitor therapy, whether adjuvant therapy should be resumed when there are signs of renewed proliferation, and whether there would be a benefit to restarting CDK4/6 inhibitors when metastasis occurs.

The monarchE trial was sponsored by Eli Lilly and Co. Dr. Harbeck disclosed research funding and speaker’s bureau activity for Lilly and others, and a consulting or advisory role with Gilead, Roche, Sanofi, Sandoz, and Seagen. Dr. Kalinsky disclosed a consulting or advisory role with multiple companies, not including Lilly.

MADRID – Five years on, the addition of the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy for women with high-risk hormone receptor–positive, HER2-negative (HR+/HER2–) early breast cancer continues to show modest but clinically significant benefits, compared with endocrine therapy alone.

Results of a planned 5-year efficacy analysis of the monarchE trial showed that at a median follow-up of 4.5 years, the abemaciclib/endocrine therapy combination was associated with a 7.6% absolute improvement in invasive disease–free survival (IDFS) and 6.7% edge in distant relapse–free survival (DRFS), compared with endocrine therapy alone, reported Nadia Harbeck, MD, from the Breast Center at Ludwig Maximilians University Hospital in Munich.

“The data are consistent with a carryover effect and further support the addition of adjuvant abemaciclib to endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive high-risk early breast cancer,” she said at the 2023 European Society for Medical Oncology Congress.
 

High recurrence risk

Although HR+/HER2– breast cancer, the most common subtype of breast cancer, is generally associated with better outcomes than other subtypes, patients with node-positive early disease are at high risk for early recurrence and need treatment intensification, Dr. Harbeck said.

The monarchE trial included two cohorts: a primary cohort consisting of patients deemed at high risk based on clinical pathological features such as the number of involved axillary nodes, grade 3 disease, and tumors 5 cm or larger, and a second cohort of patients with lower disease grade and smaller tumors but with high levels of the proliferation marker Ki-67.

A total of 5,637 patients were randomized to receive either 2 years of abemaciclib 150 mg twice daily plus endocrine therapy, or endocrine therapy alone, followed by 3-8 years of additional endocrine as clinically indicated in each study arm.

An earlier preplanned interim analysis of the phase 3 trial of more than 5,600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.

As that analysis showed, at a median follow-up of 15.5 months abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of IDFS vs. endocrine therapy alone.

At the time, the findings were hailed as practice-changing and, once approved for high-risk HR+/HER2-negative early breast cancer, as the new standard of care.

In the current analysis, Dr. Harbeck and colleagues looked at 5-year outcomes from a prespecified analysis, with a data cutoff of July 3, 2023.

All patients originally assigned to abemaciclib are now off the drug, and more than 80% have been followed for a minimum of 2 year since completing therapy with the CDK4/6 inhibitor.
 

Results

At 5 years there were cumulative totals of 407 IDFS events in the combination arm, compared with 585 in the endocrine therapy alone arm, a difference that translated into a hazard ratio of 0.68 favoring abemaciclib (P < .001).

The IDFS benefit with the combination was consistent across most subgroups, including older patients, perimenopausal and postmenopausal patients, those who had received prior neoadjuvant or adjuvant chemotherapy, all tumor sizes, number of positive lymph nodes, less favorable tumor stage or grade, and order of endocrine therapy (tamoxifen or aromatase inhibitor as first drug).

As noted before, DRFS, a secondary endpoint, also favored abemaciclib, with 345 events occurring over 5 years in the combination arm, compared with 501 in the endocrine therapy arm alone. This translated into a HR with the combination of 0.68 (P < .001).

There were fewer deaths in the abemaciclib arm (208 vs. 234), but this difference was not statistically significant.

The proportions of patients with treatment-emergent adverse events and serious adverse events (SAEs) were higher in the combination arm than in the endocrine therapy alone arm in all previous analyses of the trial data.

In the current analysis, “I would say it’s reassuring to see that the SAEs reported in the follow-up period, after the study treatment had been completed, are quite similar between the endocrine therapy alone arm and the abemaciclib plus endocrine therapy arm,” Dr. Harbeck said.
 

Changing road map

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University, Atlanta, commented that CDK4/6 inhibitors “have changed the road map for treating hormone receptor–positive, HER2-negative disease.”

To put the monarchE results in context, he compared them with those of the NATALEE trial, in which patients were randomized to endocrine therapy with or without the CDK4/6 inhibitor ribociclib (Kisqali). That combination was previously shown to provide a significant survival advantage for women with metastatic breast cancer.

In NATALEE, which included both high-risk and intermediate-risk patients with early breast cancer, the absolute difference in 3-year IDFS rates between the combination group and endocrine monotherapy groups was 3.3%.

To determine the ultimate value of combining a CDK4/6 inhibitor with endocrine therapy in early breast cancer, longer follow-up of both trials will be necessary, Dr. Kalinsky said.

“The reason that follow-up is critical for both of these studies is that for this subtype of breast cancer, based upon data including from the Early Breast Cancer Trialists Group, we can see approximately 50% of recurrences after the first 5 years, and we think of cytotoxic chemotherapy as benefiting patients within those first 5 years. And while we think of CDK4/6 inhibitors as being cytostatic drugs, we are seeing a carryover effect in which 2 years of abemaciclib is improving outcome at the 5-year landmark,” he said.

Questions that still need to be answered include the optimal duration of CDK4/6 inhibitor therapy, whether adjuvant therapy should be resumed when there are signs of renewed proliferation, and whether there would be a benefit to restarting CDK4/6 inhibitors when metastasis occurs.

The monarchE trial was sponsored by Eli Lilly and Co. Dr. Harbeck disclosed research funding and speaker’s bureau activity for Lilly and others, and a consulting or advisory role with Gilead, Roche, Sanofi, Sandoz, and Seagen. Dr. Kalinsky disclosed a consulting or advisory role with multiple companies, not including Lilly.

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The strike by health care workers at Kaiser Permanente may not involve physicians (yet). But as more doctors in the United States are finding themselves working as salaried employees, physicians can – and probably will – become a powerful force for change in a health care system that has shown itself to be increasingly hostile to employee concerns over issues involving patient care, wages and benefits, safety, and well-being.

Salaried employment has its challenges. Physician-employees may have less autonomy and voice in decision-making that affects patients. They may splinter into fragmented work groups; feel isolated; and have different imperatives based on who they are, what they want, and where they work. They may feel more removed from their patients and struggle to build strong relationships, with their employers in the way.

Yet important opportunities exist for doctors when embracing their employee side. These opportunities can help them and other health care workers fight effectively for their interests and those of patients in a corporatized health care system. Examples of these interests include adequate compensation, wellness, job security, patient and worker safety, health care quality, reasonable workloads and schedules, and fair treatment by employers, including the need to exhibit a strong collective voice in organizational decision-making.

Some believe that physician-employees must be unionized to maximize their rights and power as employees. Many expect physician unionization to take hold more fully over time. Medical residents, the doctors of tomorrow, are already considering unionization in greater numbers. Some are also doing it in the same employment setting alongside other health professionals, such as nurses.

Having studied doctors and their employment situations for years, I am convinced that whether through unionization or another approach, physicians must also change how they think about control; train and learn alongside other health care workers who share similar interests; and elevate at an early career stage their knowledge of the business side of health care.
 

Adopt a more pragmatic definition of autonomy

Doctors must embrace an updated definition of autonomy – one that matches their status as highly paid labor.

When I have spoken to physicians in my research about what autonomy means to them, many seem unable to reconceptualize it from a vague and absolute form of their profession’s strategic control over their economic fates and technical skills toward an individualized control that is situation-specific, one centered on winning the daily fights about workplace bread-and-butter issues such as those mentioned above.

But a more pragmatic definition of autonomy could get doctors focused on influencing important issues of the patient-care day and enhance their negotiating power with employers. It would allow physicians to break out of what often seems a paralysis of inaction – waiting for employers, insurers, or the government to reinstate the profession’s idealized version of control by handing it back the keys to the health care system through major regulatory, structural, and reimbursement-related changes. This fantasy is unlikely to become reality.

Physician-employees I’ve talked to over the years understand their everyday challenges. But when it comes to engaging in localized and sustained action to overcome them, they often perform less well, leading to feelings of helplessness and burnout. Valuing tactical control over their jobs and work setting will yield smaller but more impactful wins as employees intent on making their everyday work lives better.
 

Train alongside other health care professionals

Physicians must accept that how they are trained no longer prepares them for the employee world into which most are dropped. For instance, unless doctors are trained collaboratively alongside other health care professionals – such as nurses – they are less likely to identify closely with these colleagues once in practice. There is strength in numbers, so this mutual identification empowers both groups of employees. Yet, medical education remains largely the same: training young medical students in isolation for the first couple of years, then placing them into clerkships and residencies where true interprofessional care opportunities remain stunted and secondary to the “physician as captain of the team” mantra.

Unfortunately, the “hidden curriculum” of medicine helps convince medical students and residents early in their careers that they are the unquestioned leaders in patient care settings. This hierarchy encourages some doctors to keep their psychological distance from other members of the health care team and to resist sharing power, concerns, or insights with less skilled health care workers. This socialization harms the ability of physicians to act in a unified fashion alongside these other workers. Having physicians learn and train alongside other health professionals yields positive benefits for collective advocacy, including a shared sense of purpose, positive views on collaboration with others in the health setting, and greater development of bonds with nonphysician coworkers.
 

Integrate business with medical training in real time

Medical students and residents generally lack exposure to the everyday business realities of the U.S. health care system. This gap hinders their ability to understand the employee world and push for the types of changes and work conditions that benefit all health care workers. Formal business and management training should be a required part of every U.S. medical school and residency curriculum from day one. If you see it at all in medical schools now, it is mostly by accident, or given separate treatment in the form of standalone MBA or MPH degrees that rarely integrate organically and in real time with actual medical training. Not every doctor needs an MBA or MPH degree. However, all of them require a stronger contextual understanding of how the medicine they wish to practice is shaped by the economic and fiscal circumstances surrounding it – circumstances they do not control.

This is another reason why young doctors are unhappy and burned out. They cannot push for specific changes or properly critique the pros and cons of how their work is structured because they have not been made aware, in real time as they learn clinical practice, how their jobs are shaped by realities such as insurance coverage and reimbursement, the fragmentation of the care delivery system, their employer’s financial health , and the socioeconomic circumstances of their patients. They aren’t given the methods and tools related to process and quality improvement, budgeting, negotiation, risk management, leadership, and talent management that might help them navigate these undermining forces. They also get little advance exposure in their training to important workplace “soft” skills in such areas as how to work in teams, networking, communication and listening, empathy, and problem-solving – all necessary foci for bringing them closer to other health care workers and advocating alongside them effectively with health care employers.

Now is the time for physicians to embrace their identity as employees. Doing so is in their own best interest as professionals. It will help others in the health care workforce as well as patients. Moreover, it provides a needed counterbalance to the powerful corporate ethos now ascendant in U.S. health care.

Timothy Hoff, PhD, is a professor of management and healthcare systems at Northeastern University, Boston, and an associate fellow at the University of Oxford, England. He disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

The strike by health care workers at Kaiser Permanente may not involve physicians (yet). But as more doctors in the United States are finding themselves working as salaried employees, physicians can – and probably will – become a powerful force for change in a health care system that has shown itself to be increasingly hostile to employee concerns over issues involving patient care, wages and benefits, safety, and well-being.

Salaried employment has its challenges. Physician-employees may have less autonomy and voice in decision-making that affects patients. They may splinter into fragmented work groups; feel isolated; and have different imperatives based on who they are, what they want, and where they work. They may feel more removed from their patients and struggle to build strong relationships, with their employers in the way.

Yet important opportunities exist for doctors when embracing their employee side. These opportunities can help them and other health care workers fight effectively for their interests and those of patients in a corporatized health care system. Examples of these interests include adequate compensation, wellness, job security, patient and worker safety, health care quality, reasonable workloads and schedules, and fair treatment by employers, including the need to exhibit a strong collective voice in organizational decision-making.

Some believe that physician-employees must be unionized to maximize their rights and power as employees. Many expect physician unionization to take hold more fully over time. Medical residents, the doctors of tomorrow, are already considering unionization in greater numbers. Some are also doing it in the same employment setting alongside other health professionals, such as nurses.

Having studied doctors and their employment situations for years, I am convinced that whether through unionization or another approach, physicians must also change how they think about control; train and learn alongside other health care workers who share similar interests; and elevate at an early career stage their knowledge of the business side of health care.
 

Adopt a more pragmatic definition of autonomy

Doctors must embrace an updated definition of autonomy – one that matches their status as highly paid labor.

When I have spoken to physicians in my research about what autonomy means to them, many seem unable to reconceptualize it from a vague and absolute form of their profession’s strategic control over their economic fates and technical skills toward an individualized control that is situation-specific, one centered on winning the daily fights about workplace bread-and-butter issues such as those mentioned above.

But a more pragmatic definition of autonomy could get doctors focused on influencing important issues of the patient-care day and enhance their negotiating power with employers. It would allow physicians to break out of what often seems a paralysis of inaction – waiting for employers, insurers, or the government to reinstate the profession’s idealized version of control by handing it back the keys to the health care system through major regulatory, structural, and reimbursement-related changes. This fantasy is unlikely to become reality.

Physician-employees I’ve talked to over the years understand their everyday challenges. But when it comes to engaging in localized and sustained action to overcome them, they often perform less well, leading to feelings of helplessness and burnout. Valuing tactical control over their jobs and work setting will yield smaller but more impactful wins as employees intent on making their everyday work lives better.
 

Train alongside other health care professionals

Physicians must accept that how they are trained no longer prepares them for the employee world into which most are dropped. For instance, unless doctors are trained collaboratively alongside other health care professionals – such as nurses – they are less likely to identify closely with these colleagues once in practice. There is strength in numbers, so this mutual identification empowers both groups of employees. Yet, medical education remains largely the same: training young medical students in isolation for the first couple of years, then placing them into clerkships and residencies where true interprofessional care opportunities remain stunted and secondary to the “physician as captain of the team” mantra.

Unfortunately, the “hidden curriculum” of medicine helps convince medical students and residents early in their careers that they are the unquestioned leaders in patient care settings. This hierarchy encourages some doctors to keep their psychological distance from other members of the health care team and to resist sharing power, concerns, or insights with less skilled health care workers. This socialization harms the ability of physicians to act in a unified fashion alongside these other workers. Having physicians learn and train alongside other health professionals yields positive benefits for collective advocacy, including a shared sense of purpose, positive views on collaboration with others in the health setting, and greater development of bonds with nonphysician coworkers.
 

Integrate business with medical training in real time

Medical students and residents generally lack exposure to the everyday business realities of the U.S. health care system. This gap hinders their ability to understand the employee world and push for the types of changes and work conditions that benefit all health care workers. Formal business and management training should be a required part of every U.S. medical school and residency curriculum from day one. If you see it at all in medical schools now, it is mostly by accident, or given separate treatment in the form of standalone MBA or MPH degrees that rarely integrate organically and in real time with actual medical training. Not every doctor needs an MBA or MPH degree. However, all of them require a stronger contextual understanding of how the medicine they wish to practice is shaped by the economic and fiscal circumstances surrounding it – circumstances they do not control.

This is another reason why young doctors are unhappy and burned out. They cannot push for specific changes or properly critique the pros and cons of how their work is structured because they have not been made aware, in real time as they learn clinical practice, how their jobs are shaped by realities such as insurance coverage and reimbursement, the fragmentation of the care delivery system, their employer’s financial health , and the socioeconomic circumstances of their patients. They aren’t given the methods and tools related to process and quality improvement, budgeting, negotiation, risk management, leadership, and talent management that might help them navigate these undermining forces. They also get little advance exposure in their training to important workplace “soft” skills in such areas as how to work in teams, networking, communication and listening, empathy, and problem-solving – all necessary foci for bringing them closer to other health care workers and advocating alongside them effectively with health care employers.

Now is the time for physicians to embrace their identity as employees. Doing so is in their own best interest as professionals. It will help others in the health care workforce as well as patients. Moreover, it provides a needed counterbalance to the powerful corporate ethos now ascendant in U.S. health care.

Timothy Hoff, PhD, is a professor of management and healthcare systems at Northeastern University, Boston, and an associate fellow at the University of Oxford, England. He disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

The strike by health care workers at Kaiser Permanente may not involve physicians (yet). But as more doctors in the United States are finding themselves working as salaried employees, physicians can – and probably will – become a powerful force for change in a health care system that has shown itself to be increasingly hostile to employee concerns over issues involving patient care, wages and benefits, safety, and well-being.

Salaried employment has its challenges. Physician-employees may have less autonomy and voice in decision-making that affects patients. They may splinter into fragmented work groups; feel isolated; and have different imperatives based on who they are, what they want, and where they work. They may feel more removed from their patients and struggle to build strong relationships, with their employers in the way.

Yet important opportunities exist for doctors when embracing their employee side. These opportunities can help them and other health care workers fight effectively for their interests and those of patients in a corporatized health care system. Examples of these interests include adequate compensation, wellness, job security, patient and worker safety, health care quality, reasonable workloads and schedules, and fair treatment by employers, including the need to exhibit a strong collective voice in organizational decision-making.

Some believe that physician-employees must be unionized to maximize their rights and power as employees. Many expect physician unionization to take hold more fully over time. Medical residents, the doctors of tomorrow, are already considering unionization in greater numbers. Some are also doing it in the same employment setting alongside other health professionals, such as nurses.

Having studied doctors and their employment situations for years, I am convinced that whether through unionization or another approach, physicians must also change how they think about control; train and learn alongside other health care workers who share similar interests; and elevate at an early career stage their knowledge of the business side of health care.
 

Adopt a more pragmatic definition of autonomy

Doctors must embrace an updated definition of autonomy – one that matches their status as highly paid labor.

When I have spoken to physicians in my research about what autonomy means to them, many seem unable to reconceptualize it from a vague and absolute form of their profession’s strategic control over their economic fates and technical skills toward an individualized control that is situation-specific, one centered on winning the daily fights about workplace bread-and-butter issues such as those mentioned above.

But a more pragmatic definition of autonomy could get doctors focused on influencing important issues of the patient-care day and enhance their negotiating power with employers. It would allow physicians to break out of what often seems a paralysis of inaction – waiting for employers, insurers, or the government to reinstate the profession’s idealized version of control by handing it back the keys to the health care system through major regulatory, structural, and reimbursement-related changes. This fantasy is unlikely to become reality.

Physician-employees I’ve talked to over the years understand their everyday challenges. But when it comes to engaging in localized and sustained action to overcome them, they often perform less well, leading to feelings of helplessness and burnout. Valuing tactical control over their jobs and work setting will yield smaller but more impactful wins as employees intent on making their everyday work lives better.
 

Train alongside other health care professionals

Physicians must accept that how they are trained no longer prepares them for the employee world into which most are dropped. For instance, unless doctors are trained collaboratively alongside other health care professionals – such as nurses – they are less likely to identify closely with these colleagues once in practice. There is strength in numbers, so this mutual identification empowers both groups of employees. Yet, medical education remains largely the same: training young medical students in isolation for the first couple of years, then placing them into clerkships and residencies where true interprofessional care opportunities remain stunted and secondary to the “physician as captain of the team” mantra.

Unfortunately, the “hidden curriculum” of medicine helps convince medical students and residents early in their careers that they are the unquestioned leaders in patient care settings. This hierarchy encourages some doctors to keep their psychological distance from other members of the health care team and to resist sharing power, concerns, or insights with less skilled health care workers. This socialization harms the ability of physicians to act in a unified fashion alongside these other workers. Having physicians learn and train alongside other health professionals yields positive benefits for collective advocacy, including a shared sense of purpose, positive views on collaboration with others in the health setting, and greater development of bonds with nonphysician coworkers.
 

Integrate business with medical training in real time

Medical students and residents generally lack exposure to the everyday business realities of the U.S. health care system. This gap hinders their ability to understand the employee world and push for the types of changes and work conditions that benefit all health care workers. Formal business and management training should be a required part of every U.S. medical school and residency curriculum from day one. If you see it at all in medical schools now, it is mostly by accident, or given separate treatment in the form of standalone MBA or MPH degrees that rarely integrate organically and in real time with actual medical training. Not every doctor needs an MBA or MPH degree. However, all of them require a stronger contextual understanding of how the medicine they wish to practice is shaped by the economic and fiscal circumstances surrounding it – circumstances they do not control.

This is another reason why young doctors are unhappy and burned out. They cannot push for specific changes or properly critique the pros and cons of how their work is structured because they have not been made aware, in real time as they learn clinical practice, how their jobs are shaped by realities such as insurance coverage and reimbursement, the fragmentation of the care delivery system, their employer’s financial health , and the socioeconomic circumstances of their patients. They aren’t given the methods and tools related to process and quality improvement, budgeting, negotiation, risk management, leadership, and talent management that might help them navigate these undermining forces. They also get little advance exposure in their training to important workplace “soft” skills in such areas as how to work in teams, networking, communication and listening, empathy, and problem-solving – all necessary foci for bringing them closer to other health care workers and advocating alongside them effectively with health care employers.

Now is the time for physicians to embrace their identity as employees. Doing so is in their own best interest as professionals. It will help others in the health care workforce as well as patients. Moreover, it provides a needed counterbalance to the powerful corporate ethos now ascendant in U.S. health care.

Timothy Hoff, PhD, is a professor of management and healthcare systems at Northeastern University, Boston, and an associate fellow at the University of Oxford, England. He disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved nivolumab (Opdivo) for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Nivolumab, developed by Bristol-Myers Squibb, was previously approved as a single agent or in combination with ipilimumab for patients aged 12 years and older with unresectable or metastatic melanoma and for the adjuvant treatment of those aged 12 and older with completely resected stage III or IV melanoma.

The new approval was based on findings from the phase 3 CHECKMATE-76K trial, which randomly assigned 790 patients in a 2:1 ratio to receive nivolumab 480 mg or placebo by intravenous infusion. All patients in the trial had good performance status, had undergone complete resection of the primary melanoma with negative margins, and had tested negative on sentinel lymph node assessment within 12 weeks prior to randomization. Patients received treatment every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity occurred.

Nivolumab reduced the risk of recurrence or death by 58% compared with placebo (hazard ratio, 0.42). Recurrence-free survival at 1 year was 89% with treatment, vs 79.4% with placebo. Median recurrence-free survival at 5 years was not reached in either arm.

Adverse reactions that were reported in at least 20% of patients included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.

The recommended nivolumab dose for patients weighing 40 kg or more is 480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients who weigh less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Bristol-Myers Squibb’s application for approval led to the agent’s being granted orphan drug designation, allowing expedited review.

A version of this article appeared on Medscape.com.

New England Baptist Hospital has been grappling with a serious problem facing health care today: insurers demanding prior authorizations for services ordered by physicians. Meeting payers’ requirements eats up time, delays treatment, and can be a costly drain on doctors’ practices. 

To deal with this problem, the Boston orthopedic hospital has opted to automate submission of prior authorization requests on behalf of more than 100 mostly orthopedic surgeons on staff. 

After 5 years using this system, “we can say that automation definitely works,” said Lidiya Hadzhieva, director of patient access at the hospital. The software has reduced write-offs by 30% and staff costs by 25%. Prior authorization gets approved 3 days after scheduling, compared with 11 days previously, she said.

“This software not only saves staff time, but it can also more accurately predict when prior authorization is needed,” she added.

For practices deluged with required prior authorizations by insurers, automation is emerging as a way for practices to make the process less time-consuming and save money. However, the software can be costly and may not be adoptable to many practices, and many physicians are not even aware it exists.

So far, the software is mainly used at large organizations like hospital systems. But as word gets out and the software becomes easier to use, private practices and other smaller entities may join the automation trend.

There is definitely a need to automate prior authorization. The American Medical Association reports that physicians spend 16 hours per week on prior authorizations. In a recent AMA survey, more than 60% of physicians indicated that it’s difficult to know when prior authorization is needed. And 93% of physicians reported care delays while waiting for authorization, the AMA said.  

Experts estimate that 80% of prior authorization work could be automated, but most practices still use the phone or fax, even as numbers of prior authorizations continue to increase.
 

How it works

Automation software connects directly to the practice’s electronic health record (EHR). “When the doctor places an order in the EHR, the process starts automatically,” Ms. Hadzhieva said. “The doctor may not even notice it.” 

In addition to using an EHR connection, many software products can communicate with the payer through its portal or by fax or phone, while still automating other parts of the process.

The software’s first step is to decide whether prior authorization is needed. This requires having an updated list of the rules that each payer uses for prior authorization. Manually keeping track of payer rules is very time-consuming, but automation uses bots to visit each payer site to look for rules changes. One vendor, Infinitus, uses a voice-based bot called Eva that calls up each payer and speaks with a representative.

“Automatically updating payer rules is not a new technology,” said YiDing Yu, MD, chief product officer at Olive, the automation vendor for New England Baptist. “What is new in the last 5 years is extracting the information needed for the prior authorization out of the clinical notes.”

This is challenging because each doctor has different ways to describe each step of clinical work. To identify this shorthand, Dr. Yu said Olive uses natural language processing, which is a form of artificial intelligence that learns how each doctor describes things.

Dr. Yu asserts that Olive is actually better than a practice’s staff at digging out clinical information. She said staff without much clinical training may miss terms that the software can catch, and they don’t have the time to go back many months into the record to find valuable information. But automation can do that.

In some instances, however, the software may not be able to find the information, in which case it alerts staff through a prompt in the EHR and the information is retrieved manually, Dr. Yu said.

Next, the Olive software puts the information it found into the request form and sends it to the payer. After submission, the software constantly checks on the status of each request, again visiting payer sites with a bot.

At New England Baptist, the software is used mainly by physicians in fairly small private practices who are on staff. They are using the software on the hospital’s dime, but it only works inside the hospital, Ms. Hadzhieva said. For their work outside of the hospital, they would have to purchase the Olive software on their own, she said.
 

Automation hasn’t spread to practices yet

Despite the promising outcomes for products like Olive, automation software is still primarily used by large organizations. Vendors say very few private practices have bought it yet. “The technology works, but it is still in the early-adopter phase,” Dr. Yu said.

For one thing, the software can be expensive. Very few vendors reveal their prices, but Dr. Yu did so. She said Olive normally costs about $50,000 a year for even a small organization. She insisted, however, that the savings from avoiding just one denial each month for a hip surgery would justify the expense.

On the other hand, some automation software is free, such as the Surescripts product for prior authorization of prescriptions. But it is unclear whether Surescripts does as much as Olive. Vendors’ descriptions of their products tend to be vague.

Also, Surescripts and Olive have entirely separate functions. Dr. Yu said Olive is limited to procedures, so it benefits specialties like oncology, neurosurgery, colorectal surgery, vascular surgery, and cardiology. Olive does not cover prescriptions, because they operate on a different technology.

Dr. Yu said another hurdle for adopting the software is the kind of EHR systems that doctors use. At this point, only a few EHR systems – such as Epic, Cerner, and Athena – are compatible with Olive. Large organizations tend to use Epic and Cerner, while many practices often use Athena or a variety of other systems, she said.

Despite stunted demand, there is no shortage of companies offering automation software for medical (that is, non-prescription) prior authorization. One compilation lists 25 such vendors, including companies like Myndshft, Rhyme, Infinitus, Infinx, and Waystar. As with any start-up technology, companies occasionally buy each other out.

In addition to issues like cost, specialty, and EHR compatibility, another hurdle is that few doctors even know the technology exists. Vendors say marketing focuses on larger provider organizations, not smaller practices.

Even many tech-savvy doctors, like Adam Bruggeman, MD, an orthopedist and CEO of Texas Spine Care Center in San Antonio, say they know little about the technology. “There is definitely a need to automate prior authorization,” he said. “But I don’t know of any colleagues who use it.” He has only just begun to explore vendors, he said.

Many medical practice consultants also have not yet explored the technology. “Automation makes a lot of sense, because there are a lot of repetitive tasks in prior authorization,” said Jill Arena, CEO of Portland, Ore.–based Health e Practices. “But I haven’t looked into it yet, and none of my clients has even asked about it.”

“I could see how it could be an easier sell for large organizations,” she added. “They have an IT person and a CFO who can explore the issue. Smaller practices usually don’t have that kind of expertise.”
 

Where does automation go from here?

Until now, clinicians who want to fully automate prior authorizations would have to buy two products – one for medical procedures and one for prescriptions. This has to do with incompatible electronic transmission standards, which are used to digitize information, said Susan Lawson-Dawson, content marketing strategist for the vendor Myndshft Health.

Myndshft has long been selling automation software for medical prior authorizations, but now it is introducing a product for prescriptions, Ms. Lawson-Dawson said. She said Myndshft will then be the only vendor to automate both kinds of prior authorizations.

Ms. Lawson-Dawson said Myndshft has 685 customers to date and is looking for more business. Recently the company entered the Google Cloud Marketplace. Google Cloud customers can now direct their committed spend with Google to purchasing Myndshft, meaning they could get it at a discount.

Software like Olive and Myndshft can operate independently of payers, but a vendor called Rhyme depends on payers for its software to function, said Rhyme CEO Joe Anstine. He said more than 300 payers have agreed to install the Rhyme system, and Rhyme has signed up a number of large health systems to use the product. Initially, he said, clinicians paid for the service, but now Rhyme is beginning to find payers to foot the costs and to let clinicians use it for free, which would open Rhyme up to smaller practices.

EHR companies themselves are beginning to offer automation, too. Epic, for example, has created a tool for prior authorization as part of its Epic Payer Platform. Like Rhyme, it requires payer cooperation, because information goes back and forth between clinician and payer in what is called bi-directional exchange.

The Epic product is still in its pilot phase. Epic reported that several large health systems were using its product in conjunction with a specific payer – for instance, Mayo Clinic with Blue Cross and Blue Shield of Minnesota and Ochsner Health with Humana. According to Epic, the arrangement reduced Mayo’s denials due to additional documentation requests by 63% for professional billing.

Automating with just one payer still means the clinician has to deal with manual processes at other payers, but a large clinician could have sufficient volume with that one payer to make the arrangement useful.
 

Will payers automate prior authorization?

Ultimately, payers may take the automation business away from vendors, offering a free product to all clinicians. But don’t hold your breath. Payers first have to rebuild their electronic systems to accommodate an electronic connection with providers. Even then, some payers might hold back from automating, forcing practices to continue manually processing some prior authorizations.

Efforts are underway, however, to mandate payers to support prior authorization automation. For this to happen, payers would have to revamp their data so that it could be easily read by practices’ EHRs. This would mean adopting a specific interoperability standard called Health Level 7 Fast Healthcare Interoperability Resources (FHIR).

Toward this goal, the Centers for Medicare & Medicaid Services proposes to require payers to adopt FHIR by January 2026. (CMS still has to finalize the rule.) Experts say the two-year ramp-up time is needed because it takes extensive work for payers to translate their data into FHIR.

The only payer so far to switch to FHIR for prior authorization is Regence in Washington state. In a pilot project, it has automated prior authorization with just one provider, MultiCare Connected Care, an accountable care organization (ACO), also in Washington state.

Anna Taylor, associate vice president of population health and value-based care at MultiCare, explained how the arrangement works. “Two separate entities are sharing one operational process,” she told this news organization. “That means they can have a digital conversation back and forth, so it is much easier to resolve prior authorization issues.” 

Unlike many vendor products, the Regence service is free. And while the vendors market only to large organizations, most doctors in the MultiCare arrangement are in independent practices. Ms. Taylor said these doctors have been “enthusiastic” about the arrangement.

The results of the pilot are impressive. Ms. Taylor said automation has resulted in a 233% productivity gain for MultiCare clinicians, and 89% of submissions to Regence get an immediate response.

There is a potential downside, however, to working directly with payers. A direct connection to clinicians allows payers to access the doctor’s clinical notes, which could make many doctors uneasy. But Ms. Taylor said Regence only has access to the “discrete data fields” on MultiCare’s EHR dashboard, not to the notes themselves.

The ultimate goal of the Regence-Multicare project is to include more payers and clinicians. Ms. Taylor said two of the 27 other payers that MultiCare works with are “highly interested,” but it would take a lot of work for them to get connected with practices and other clinicians. 

Ultimately, payers could offer automation and third-party vendors might then fade away. However, physicians may resist working directly with payers if the arrangement requires full access to their medical records.

A version of this article first appeared on Medscape.com.

New England Baptist Hospital has been grappling with a serious problem facing health care today: insurers demanding prior authorizations for services ordered by physicians. Meeting payers’ requirements eats up time, delays treatment, and can be a costly drain on doctors’ practices. 

To deal with this problem, the Boston orthopedic hospital has opted to automate submission of prior authorization requests on behalf of more than 100 mostly orthopedic surgeons on staff. 

After 5 years using this system, “we can say that automation definitely works,” said Lidiya Hadzhieva, director of patient access at the hospital. The software has reduced write-offs by 30% and staff costs by 25%. Prior authorization gets approved 3 days after scheduling, compared with 11 days previously, she said.

“This software not only saves staff time, but it can also more accurately predict when prior authorization is needed,” she added.

For practices deluged with required prior authorizations by insurers, automation is emerging as a way for practices to make the process less time-consuming and save money. However, the software can be costly and may not be adoptable to many practices, and many physicians are not even aware it exists.

So far, the software is mainly used at large organizations like hospital systems. But as word gets out and the software becomes easier to use, private practices and other smaller entities may join the automation trend.

There is definitely a need to automate prior authorization. The American Medical Association reports that physicians spend 16 hours per week on prior authorizations. In a recent AMA survey, more than 60% of physicians indicated that it’s difficult to know when prior authorization is needed. And 93% of physicians reported care delays while waiting for authorization, the AMA said.  

Experts estimate that 80% of prior authorization work could be automated, but most practices still use the phone or fax, even as numbers of prior authorizations continue to increase.
 

How it works

Automation software connects directly to the practice’s electronic health record (EHR). “When the doctor places an order in the EHR, the process starts automatically,” Ms. Hadzhieva said. “The doctor may not even notice it.” 

In addition to using an EHR connection, many software products can communicate with the payer through its portal or by fax or phone, while still automating other parts of the process.

The software’s first step is to decide whether prior authorization is needed. This requires having an updated list of the rules that each payer uses for prior authorization. Manually keeping track of payer rules is very time-consuming, but automation uses bots to visit each payer site to look for rules changes. One vendor, Infinitus, uses a voice-based bot called Eva that calls up each payer and speaks with a representative.

“Automatically updating payer rules is not a new technology,” said YiDing Yu, MD, chief product officer at Olive, the automation vendor for New England Baptist. “What is new in the last 5 years is extracting the information needed for the prior authorization out of the clinical notes.”

This is challenging because each doctor has different ways to describe each step of clinical work. To identify this shorthand, Dr. Yu said Olive uses natural language processing, which is a form of artificial intelligence that learns how each doctor describes things.

Dr. Yu asserts that Olive is actually better than a practice’s staff at digging out clinical information. She said staff without much clinical training may miss terms that the software can catch, and they don’t have the time to go back many months into the record to find valuable information. But automation can do that.

In some instances, however, the software may not be able to find the information, in which case it alerts staff through a prompt in the EHR and the information is retrieved manually, Dr. Yu said.

Next, the Olive software puts the information it found into the request form and sends it to the payer. After submission, the software constantly checks on the status of each request, again visiting payer sites with a bot.

At New England Baptist, the software is used mainly by physicians in fairly small private practices who are on staff. They are using the software on the hospital’s dime, but it only works inside the hospital, Ms. Hadzhieva said. For their work outside of the hospital, they would have to purchase the Olive software on their own, she said.
 

Automation hasn’t spread to practices yet

Despite the promising outcomes for products like Olive, automation software is still primarily used by large organizations. Vendors say very few private practices have bought it yet. “The technology works, but it is still in the early-adopter phase,” Dr. Yu said.

For one thing, the software can be expensive. Very few vendors reveal their prices, but Dr. Yu did so. She said Olive normally costs about $50,000 a year for even a small organization. She insisted, however, that the savings from avoiding just one denial each month for a hip surgery would justify the expense.

On the other hand, some automation software is free, such as the Surescripts product for prior authorization of prescriptions. But it is unclear whether Surescripts does as much as Olive. Vendors’ descriptions of their products tend to be vague.

Also, Surescripts and Olive have entirely separate functions. Dr. Yu said Olive is limited to procedures, so it benefits specialties like oncology, neurosurgery, colorectal surgery, vascular surgery, and cardiology. Olive does not cover prescriptions, because they operate on a different technology.

Dr. Yu said another hurdle for adopting the software is the kind of EHR systems that doctors use. At this point, only a few EHR systems – such as Epic, Cerner, and Athena – are compatible with Olive. Large organizations tend to use Epic and Cerner, while many practices often use Athena or a variety of other systems, she said.

Despite stunted demand, there is no shortage of companies offering automation software for medical (that is, non-prescription) prior authorization. One compilation lists 25 such vendors, including companies like Myndshft, Rhyme, Infinitus, Infinx, and Waystar. As with any start-up technology, companies occasionally buy each other out.

In addition to issues like cost, specialty, and EHR compatibility, another hurdle is that few doctors even know the technology exists. Vendors say marketing focuses on larger provider organizations, not smaller practices.

Even many tech-savvy doctors, like Adam Bruggeman, MD, an orthopedist and CEO of Texas Spine Care Center in San Antonio, say they know little about the technology. “There is definitely a need to automate prior authorization,” he said. “But I don’t know of any colleagues who use it.” He has only just begun to explore vendors, he said.

Many medical practice consultants also have not yet explored the technology. “Automation makes a lot of sense, because there are a lot of repetitive tasks in prior authorization,” said Jill Arena, CEO of Portland, Ore.–based Health e Practices. “But I haven’t looked into it yet, and none of my clients has even asked about it.”

“I could see how it could be an easier sell for large organizations,” she added. “They have an IT person and a CFO who can explore the issue. Smaller practices usually don’t have that kind of expertise.”
 

Where does automation go from here?

Until now, clinicians who want to fully automate prior authorizations would have to buy two products – one for medical procedures and one for prescriptions. This has to do with incompatible electronic transmission standards, which are used to digitize information, said Susan Lawson-Dawson, content marketing strategist for the vendor Myndshft Health.

Myndshft has long been selling automation software for medical prior authorizations, but now it is introducing a product for prescriptions, Ms. Lawson-Dawson said. She said Myndshft will then be the only vendor to automate both kinds of prior authorizations.

Ms. Lawson-Dawson said Myndshft has 685 customers to date and is looking for more business. Recently the company entered the Google Cloud Marketplace. Google Cloud customers can now direct their committed spend with Google to purchasing Myndshft, meaning they could get it at a discount.

Software like Olive and Myndshft can operate independently of payers, but a vendor called Rhyme depends on payers for its software to function, said Rhyme CEO Joe Anstine. He said more than 300 payers have agreed to install the Rhyme system, and Rhyme has signed up a number of large health systems to use the product. Initially, he said, clinicians paid for the service, but now Rhyme is beginning to find payers to foot the costs and to let clinicians use it for free, which would open Rhyme up to smaller practices.

EHR companies themselves are beginning to offer automation, too. Epic, for example, has created a tool for prior authorization as part of its Epic Payer Platform. Like Rhyme, it requires payer cooperation, because information goes back and forth between clinician and payer in what is called bi-directional exchange.

The Epic product is still in its pilot phase. Epic reported that several large health systems were using its product in conjunction with a specific payer – for instance, Mayo Clinic with Blue Cross and Blue Shield of Minnesota and Ochsner Health with Humana. According to Epic, the arrangement reduced Mayo’s denials due to additional documentation requests by 63% for professional billing.

Automating with just one payer still means the clinician has to deal with manual processes at other payers, but a large clinician could have sufficient volume with that one payer to make the arrangement useful.
 

Will payers automate prior authorization?

Ultimately, payers may take the automation business away from vendors, offering a free product to all clinicians. But don’t hold your breath. Payers first have to rebuild their electronic systems to accommodate an electronic connection with providers. Even then, some payers might hold back from automating, forcing practices to continue manually processing some prior authorizations.

Efforts are underway, however, to mandate payers to support prior authorization automation. For this to happen, payers would have to revamp their data so that it could be easily read by practices’ EHRs. This would mean adopting a specific interoperability standard called Health Level 7 Fast Healthcare Interoperability Resources (FHIR).

Toward this goal, the Centers for Medicare & Medicaid Services proposes to require payers to adopt FHIR by January 2026. (CMS still has to finalize the rule.) Experts say the two-year ramp-up time is needed because it takes extensive work for payers to translate their data into FHIR.

The only payer so far to switch to FHIR for prior authorization is Regence in Washington state. In a pilot project, it has automated prior authorization with just one provider, MultiCare Connected Care, an accountable care organization (ACO), also in Washington state.

Anna Taylor, associate vice president of population health and value-based care at MultiCare, explained how the arrangement works. “Two separate entities are sharing one operational process,” she told this news organization. “That means they can have a digital conversation back and forth, so it is much easier to resolve prior authorization issues.” 

Unlike many vendor products, the Regence service is free. And while the vendors market only to large organizations, most doctors in the MultiCare arrangement are in independent practices. Ms. Taylor said these doctors have been “enthusiastic” about the arrangement.

The results of the pilot are impressive. Ms. Taylor said automation has resulted in a 233% productivity gain for MultiCare clinicians, and 89% of submissions to Regence get an immediate response.

There is a potential downside, however, to working directly with payers. A direct connection to clinicians allows payers to access the doctor’s clinical notes, which could make many doctors uneasy. But Ms. Taylor said Regence only has access to the “discrete data fields” on MultiCare’s EHR dashboard, not to the notes themselves.

The ultimate goal of the Regence-Multicare project is to include more payers and clinicians. Ms. Taylor said two of the 27 other payers that MultiCare works with are “highly interested,” but it would take a lot of work for them to get connected with practices and other clinicians. 

Ultimately, payers could offer automation and third-party vendors might then fade away. However, physicians may resist working directly with payers if the arrangement requires full access to their medical records.

A version of this article first appeared on Medscape.com.

New England Baptist Hospital has been grappling with a serious problem facing health care today: insurers demanding prior authorizations for services ordered by physicians. Meeting payers’ requirements eats up time, delays treatment, and can be a costly drain on doctors’ practices. 

To deal with this problem, the Boston orthopedic hospital has opted to automate submission of prior authorization requests on behalf of more than 100 mostly orthopedic surgeons on staff. 

After 5 years using this system, “we can say that automation definitely works,” said Lidiya Hadzhieva, director of patient access at the hospital. The software has reduced write-offs by 30% and staff costs by 25%. Prior authorization gets approved 3 days after scheduling, compared with 11 days previously, she said.

“This software not only saves staff time, but it can also more accurately predict when prior authorization is needed,” she added.

For practices deluged with required prior authorizations by insurers, automation is emerging as a way for practices to make the process less time-consuming and save money. However, the software can be costly and may not be adoptable to many practices, and many physicians are not even aware it exists.

So far, the software is mainly used at large organizations like hospital systems. But as word gets out and the software becomes easier to use, private practices and other smaller entities may join the automation trend.

There is definitely a need to automate prior authorization. The American Medical Association reports that physicians spend 16 hours per week on prior authorizations. In a recent AMA survey, more than 60% of physicians indicated that it’s difficult to know when prior authorization is needed. And 93% of physicians reported care delays while waiting for authorization, the AMA said.  

Experts estimate that 80% of prior authorization work could be automated, but most practices still use the phone or fax, even as numbers of prior authorizations continue to increase.
 

How it works

Automation software connects directly to the practice’s electronic health record (EHR). “When the doctor places an order in the EHR, the process starts automatically,” Ms. Hadzhieva said. “The doctor may not even notice it.” 

In addition to using an EHR connection, many software products can communicate with the payer through its portal or by fax or phone, while still automating other parts of the process.

The software’s first step is to decide whether prior authorization is needed. This requires having an updated list of the rules that each payer uses for prior authorization. Manually keeping track of payer rules is very time-consuming, but automation uses bots to visit each payer site to look for rules changes. One vendor, Infinitus, uses a voice-based bot called Eva that calls up each payer and speaks with a representative.

“Automatically updating payer rules is not a new technology,” said YiDing Yu, MD, chief product officer at Olive, the automation vendor for New England Baptist. “What is new in the last 5 years is extracting the information needed for the prior authorization out of the clinical notes.”

This is challenging because each doctor has different ways to describe each step of clinical work. To identify this shorthand, Dr. Yu said Olive uses natural language processing, which is a form of artificial intelligence that learns how each doctor describes things.

Dr. Yu asserts that Olive is actually better than a practice’s staff at digging out clinical information. She said staff without much clinical training may miss terms that the software can catch, and they don’t have the time to go back many months into the record to find valuable information. But automation can do that.

In some instances, however, the software may not be able to find the information, in which case it alerts staff through a prompt in the EHR and the information is retrieved manually, Dr. Yu said.

Next, the Olive software puts the information it found into the request form and sends it to the payer. After submission, the software constantly checks on the status of each request, again visiting payer sites with a bot.

At New England Baptist, the software is used mainly by physicians in fairly small private practices who are on staff. They are using the software on the hospital’s dime, but it only works inside the hospital, Ms. Hadzhieva said. For their work outside of the hospital, they would have to purchase the Olive software on their own, she said.
 

Automation hasn’t spread to practices yet

Despite the promising outcomes for products like Olive, automation software is still primarily used by large organizations. Vendors say very few private practices have bought it yet. “The technology works, but it is still in the early-adopter phase,” Dr. Yu said.

For one thing, the software can be expensive. Very few vendors reveal their prices, but Dr. Yu did so. She said Olive normally costs about $50,000 a year for even a small organization. She insisted, however, that the savings from avoiding just one denial each month for a hip surgery would justify the expense.

On the other hand, some automation software is free, such as the Surescripts product for prior authorization of prescriptions. But it is unclear whether Surescripts does as much as Olive. Vendors’ descriptions of their products tend to be vague.

Also, Surescripts and Olive have entirely separate functions. Dr. Yu said Olive is limited to procedures, so it benefits specialties like oncology, neurosurgery, colorectal surgery, vascular surgery, and cardiology. Olive does not cover prescriptions, because they operate on a different technology.

Dr. Yu said another hurdle for adopting the software is the kind of EHR systems that doctors use. At this point, only a few EHR systems – such as Epic, Cerner, and Athena – are compatible with Olive. Large organizations tend to use Epic and Cerner, while many practices often use Athena or a variety of other systems, she said.

Despite stunted demand, there is no shortage of companies offering automation software for medical (that is, non-prescription) prior authorization. One compilation lists 25 such vendors, including companies like Myndshft, Rhyme, Infinitus, Infinx, and Waystar. As with any start-up technology, companies occasionally buy each other out.

In addition to issues like cost, specialty, and EHR compatibility, another hurdle is that few doctors even know the technology exists. Vendors say marketing focuses on larger provider organizations, not smaller practices.

Even many tech-savvy doctors, like Adam Bruggeman, MD, an orthopedist and CEO of Texas Spine Care Center in San Antonio, say they know little about the technology. “There is definitely a need to automate prior authorization,” he said. “But I don’t know of any colleagues who use it.” He has only just begun to explore vendors, he said.

Many medical practice consultants also have not yet explored the technology. “Automation makes a lot of sense, because there are a lot of repetitive tasks in prior authorization,” said Jill Arena, CEO of Portland, Ore.–based Health e Practices. “But I haven’t looked into it yet, and none of my clients has even asked about it.”

“I could see how it could be an easier sell for large organizations,” she added. “They have an IT person and a CFO who can explore the issue. Smaller practices usually don’t have that kind of expertise.”
 

Where does automation go from here?

Until now, clinicians who want to fully automate prior authorizations would have to buy two products – one for medical procedures and one for prescriptions. This has to do with incompatible electronic transmission standards, which are used to digitize information, said Susan Lawson-Dawson, content marketing strategist for the vendor Myndshft Health.

Myndshft has long been selling automation software for medical prior authorizations, but now it is introducing a product for prescriptions, Ms. Lawson-Dawson said. She said Myndshft will then be the only vendor to automate both kinds of prior authorizations.

Ms. Lawson-Dawson said Myndshft has 685 customers to date and is looking for more business. Recently the company entered the Google Cloud Marketplace. Google Cloud customers can now direct their committed spend with Google to purchasing Myndshft, meaning they could get it at a discount.

Software like Olive and Myndshft can operate independently of payers, but a vendor called Rhyme depends on payers for its software to function, said Rhyme CEO Joe Anstine. He said more than 300 payers have agreed to install the Rhyme system, and Rhyme has signed up a number of large health systems to use the product. Initially, he said, clinicians paid for the service, but now Rhyme is beginning to find payers to foot the costs and to let clinicians use it for free, which would open Rhyme up to smaller practices.

EHR companies themselves are beginning to offer automation, too. Epic, for example, has created a tool for prior authorization as part of its Epic Payer Platform. Like Rhyme, it requires payer cooperation, because information goes back and forth between clinician and payer in what is called bi-directional exchange.

The Epic product is still in its pilot phase. Epic reported that several large health systems were using its product in conjunction with a specific payer – for instance, Mayo Clinic with Blue Cross and Blue Shield of Minnesota and Ochsner Health with Humana. According to Epic, the arrangement reduced Mayo’s denials due to additional documentation requests by 63% for professional billing.

Automating with just one payer still means the clinician has to deal with manual processes at other payers, but a large clinician could have sufficient volume with that one payer to make the arrangement useful.
 

Will payers automate prior authorization?

Ultimately, payers may take the automation business away from vendors, offering a free product to all clinicians. But don’t hold your breath. Payers first have to rebuild their electronic systems to accommodate an electronic connection with providers. Even then, some payers might hold back from automating, forcing practices to continue manually processing some prior authorizations.

Efforts are underway, however, to mandate payers to support prior authorization automation. For this to happen, payers would have to revamp their data so that it could be easily read by practices’ EHRs. This would mean adopting a specific interoperability standard called Health Level 7 Fast Healthcare Interoperability Resources (FHIR).

Toward this goal, the Centers for Medicare & Medicaid Services proposes to require payers to adopt FHIR by January 2026. (CMS still has to finalize the rule.) Experts say the two-year ramp-up time is needed because it takes extensive work for payers to translate their data into FHIR.

The only payer so far to switch to FHIR for prior authorization is Regence in Washington state. In a pilot project, it has automated prior authorization with just one provider, MultiCare Connected Care, an accountable care organization (ACO), also in Washington state.

Anna Taylor, associate vice president of population health and value-based care at MultiCare, explained how the arrangement works. “Two separate entities are sharing one operational process,” she told this news organization. “That means they can have a digital conversation back and forth, so it is much easier to resolve prior authorization issues.” 

Unlike many vendor products, the Regence service is free. And while the vendors market only to large organizations, most doctors in the MultiCare arrangement are in independent practices. Ms. Taylor said these doctors have been “enthusiastic” about the arrangement.

The results of the pilot are impressive. Ms. Taylor said automation has resulted in a 233% productivity gain for MultiCare clinicians, and 89% of submissions to Regence get an immediate response.

There is a potential downside, however, to working directly with payers. A direct connection to clinicians allows payers to access the doctor’s clinical notes, which could make many doctors uneasy. But Ms. Taylor said Regence only has access to the “discrete data fields” on MultiCare’s EHR dashboard, not to the notes themselves.

The ultimate goal of the Regence-Multicare project is to include more payers and clinicians. Ms. Taylor said two of the 27 other payers that MultiCare works with are “highly interested,” but it would take a lot of work for them to get connected with practices and other clinicians. 

Ultimately, payers could offer automation and third-party vendors might then fade away. However, physicians may resist working directly with payers if the arrangement requires full access to their medical records.

A version of this article first appeared on Medscape.com.