Key clinical point: Ibrutinib maintenance (I-M; dose 560 mg daily) for 4 years is effective in patients with treatment-naive mantle cell lymphoma (MCL) who are responsive to frontline chemo-immunotherapy with significant but manageable toxicities.

Major finding: The 3-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 97%, whereas the 5-year PFS and OS rates were 89% and 91%, respectively. In patients with prior autologous stem cell transplantation (autoSCT), the 5-year PFS and OS rates were 100% each. The most common treatment-related adverse event was infection (86%; grades 1-2), and the most common grade 3-4 toxicities were hematologic.

Study details: This multicenter phase 2 study included patients with treatment-naive MCL who achieved a complete or partial response to frontline intensive induction chemo-immunotherapy with or without autoSCT and received 560 mg I-M daily for 4 years.

Disclosures: This study was supported by Pharmacyclics and Janssen. R Karmali and B Pro declared serving as consultants, speakers, or advisory board members for or receiving research funding or honoraria from various sources.

Source: Karmali R et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 (Sep 27). doi: 10.1182/bloodadvances.2023011271

Key clinical point: Ibrutinib maintenance (I-M; dose 560 mg daily) for 4 years is effective in patients with treatment-naive mantle cell lymphoma (MCL) who are responsive to frontline chemo-immunotherapy with significant but manageable toxicities.

Major finding: The 3-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 97%, whereas the 5-year PFS and OS rates were 89% and 91%, respectively. In patients with prior autologous stem cell transplantation (autoSCT), the 5-year PFS and OS rates were 100% each. The most common treatment-related adverse event was infection (86%; grades 1-2), and the most common grade 3-4 toxicities were hematologic.

Study details: This multicenter phase 2 study included patients with treatment-naive MCL who achieved a complete or partial response to frontline intensive induction chemo-immunotherapy with or without autoSCT and received 560 mg I-M daily for 4 years.

Disclosures: This study was supported by Pharmacyclics and Janssen. R Karmali and B Pro declared serving as consultants, speakers, or advisory board members for or receiving research funding or honoraria from various sources.

Source: Karmali R et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 (Sep 27). doi: 10.1182/bloodadvances.2023011271

Key clinical point: Ibrutinib maintenance (I-M; dose 560 mg daily) for 4 years is effective in patients with treatment-naive mantle cell lymphoma (MCL) who are responsive to frontline chemo-immunotherapy with significant but manageable toxicities.

Major finding: The 3-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 97%, whereas the 5-year PFS and OS rates were 89% and 91%, respectively. In patients with prior autologous stem cell transplantation (autoSCT), the 5-year PFS and OS rates were 100% each. The most common treatment-related adverse event was infection (86%; grades 1-2), and the most common grade 3-4 toxicities were hematologic.

Study details: This multicenter phase 2 study included patients with treatment-naive MCL who achieved a complete or partial response to frontline intensive induction chemo-immunotherapy with or without autoSCT and received 560 mg I-M daily for 4 years.

Disclosures: This study was supported by Pharmacyclics and Janssen. R Karmali and B Pro declared serving as consultants, speakers, or advisory board members for or receiving research funding or honoraria from various sources.

Source: Karmali R et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 (Sep 27). doi: 10.1182/bloodadvances.2023011271

Key clinical point: Prophylaxis with high-dose methotrexate (HD-MTX) was not associated with a clinically meaningful reduction in the risk for central nervous system (CNS) progression in high-risk patients with aggressive B-cell lymphoma (BCL).

Major finding: Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30).

Study details: This multicenter retrospective study included 2418 adults with aggressive BCL and a high risk for CNS progression treated with curative-intent anti-CD20-based chemoimmunotherapy who did or did not receive HD-MTX, of whom 1616 achieved a complete response.

Disclosures: This study was funded by Janssen Pharmaceuticals and others. All authors except TC El-Galaly declared serving as consultants, advisors, or speakers for or receiving honoraria, research funding, or travel support from various sources, including Janssen.

Source: Lewis KL et al on behalf of the International CNS Prophylaxis Study Group. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol. 2023 (Oct 5). doi: 10.1200/JCO.23.00365

Key clinical point: Prophylaxis with high-dose methotrexate (HD-MTX) was not associated with a clinically meaningful reduction in the risk for central nervous system (CNS) progression in high-risk patients with aggressive B-cell lymphoma (BCL).

Major finding: Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30).

Study details: This multicenter retrospective study included 2418 adults with aggressive BCL and a high risk for CNS progression treated with curative-intent anti-CD20-based chemoimmunotherapy who did or did not receive HD-MTX, of whom 1616 achieved a complete response.

Disclosures: This study was funded by Janssen Pharmaceuticals and others. All authors except TC El-Galaly declared serving as consultants, advisors, or speakers for or receiving honoraria, research funding, or travel support from various sources, including Janssen.

Source: Lewis KL et al on behalf of the International CNS Prophylaxis Study Group. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol. 2023 (Oct 5). doi: 10.1200/JCO.23.00365

Key clinical point: Prophylaxis with high-dose methotrexate (HD-MTX) was not associated with a clinically meaningful reduction in the risk for central nervous system (CNS) progression in high-risk patients with aggressive B-cell lymphoma (BCL).

Major finding: Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30).

Study details: This multicenter retrospective study included 2418 adults with aggressive BCL and a high risk for CNS progression treated with curative-intent anti-CD20-based chemoimmunotherapy who did or did not receive HD-MTX, of whom 1616 achieved a complete response.

Disclosures: This study was funded by Janssen Pharmaceuticals and others. All authors except TC El-Galaly declared serving as consultants, advisors, or speakers for or receiving honoraria, research funding, or travel support from various sources, including Janssen.

Source: Lewis KL et al on behalf of the International CNS Prophylaxis Study Group. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol. 2023 (Oct 5). doi: 10.1200/JCO.23.00365

Key clinical point: Second-line vs later-line zanubrutinib treatment leads to significantly improved long-term survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (adjusted hazard ratio 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib.

Study details: Findings are from an updated pooled analysis of 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had relapsed or refractory MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib.

Disclosures: The BGB-3111-AU-003 and BGB-3111-206 trials were sponsored by BeiGene. C Fang and S Sun declared being employees of BeiGene Co., Ltd., China. The other authors declared no conflicts of interest.

Source: Song Y et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis. Cancer Med. 2023;12(18):18643-18653 (Sep 14). doi: 10.1002/cam4.6473

Key clinical point: Second-line vs later-line zanubrutinib treatment leads to significantly improved long-term survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (adjusted hazard ratio 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib.

Study details: Findings are from an updated pooled analysis of 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had relapsed or refractory MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib.

Disclosures: The BGB-3111-AU-003 and BGB-3111-206 trials were sponsored by BeiGene. C Fang and S Sun declared being employees of BeiGene Co., Ltd., China. The other authors declared no conflicts of interest.

Source: Song Y et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis. Cancer Med. 2023;12(18):18643-18653 (Sep 14). doi: 10.1002/cam4.6473

Key clinical point: Second-line vs later-line zanubrutinib treatment leads to significantly improved long-term survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (adjusted hazard ratio 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib.

Study details: Findings are from an updated pooled analysis of 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had relapsed or refractory MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib.

Disclosures: The BGB-3111-AU-003 and BGB-3111-206 trials were sponsored by BeiGene. C Fang and S Sun declared being employees of BeiGene Co., Ltd., China. The other authors declared no conflicts of interest.

Source: Song Y et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis. Cancer Med. 2023;12(18):18643-18653 (Sep 14). doi: 10.1002/cam4.6473

Key clinical point: Second-line axicabtagene ciloleucel (axi-cel) provides high response rates and manageable safety in patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem-cell transplantation (ASCT).

Major finding: At 3 months from axi-cel infusion, the complete metabolic response rate was 71.0% (95% CI 58.1%-81.8%). At a 12-month median follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 8.1% and 14.5% of patients, respectively.

Study details: Findings are from the phase 2 ALYCANTE trial including 62 ASCT-ineligible patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel.

Disclosures: This study was funded by Kite, a Gilead company. Some authors declared serving as members of directors’ boards or advisory committees of or receiving honoraria, research funding, consulting fees, or travel or accommodation expenses from various sources, including Kite and Gilead.

Source: Houot R et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: A phase 2 trial. Nat Med. 2023;29:2593-2601 (Sep 14). doi: 10.1038/s41591-023-02572-5

Key clinical point: Second-line axicabtagene ciloleucel (axi-cel) provides high response rates and manageable safety in patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem-cell transplantation (ASCT).

Major finding: At 3 months from axi-cel infusion, the complete metabolic response rate was 71.0% (95% CI 58.1%-81.8%). At a 12-month median follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 8.1% and 14.5% of patients, respectively.

Study details: Findings are from the phase 2 ALYCANTE trial including 62 ASCT-ineligible patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel.

Disclosures: This study was funded by Kite, a Gilead company. Some authors declared serving as members of directors’ boards or advisory committees of or receiving honoraria, research funding, consulting fees, or travel or accommodation expenses from various sources, including Kite and Gilead.

Source: Houot R et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: A phase 2 trial. Nat Med. 2023;29:2593-2601 (Sep 14). doi: 10.1038/s41591-023-02572-5

Key clinical point: Second-line axicabtagene ciloleucel (axi-cel) provides high response rates and manageable safety in patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem-cell transplantation (ASCT).

Major finding: At 3 months from axi-cel infusion, the complete metabolic response rate was 71.0% (95% CI 58.1%-81.8%). At a 12-month median follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 8.1% and 14.5% of patients, respectively.

Study details: Findings are from the phase 2 ALYCANTE trial including 62 ASCT-ineligible patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel.

Disclosures: This study was funded by Kite, a Gilead company. Some authors declared serving as members of directors’ boards or advisory committees of or receiving honoraria, research funding, consulting fees, or travel or accommodation expenses from various sources, including Kite and Gilead.

Source: Houot R et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: A phase 2 trial. Nat Med. 2023;29:2593-2601 (Sep 14). doi: 10.1038/s41591-023-02572-5

Alectinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, significantly improved disease-free survival (DFS) at 2 years, compared with chemotherapy, in patients with completely resected ALK+ non–small cell lung cancer (NSCLC), according to interim findings from the open-label phase 3 ALINA trial.

The results suggest that alectinib, which is currently the first-line treatment choice in more advanced NSCLC, also provides an effective new treatment strategy for patients with resected ALK+ NSCLC, said Ben Solomon, MBBS, PhD, who presented late-breaking data from the trial at the annual meeting of the European Society for Medical Oncology.

ALINA is the first phase 3 trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease, said Dr. Solomon, professor and medical oncologist at Peter MacCallum Cancer Centre, Melbourne.

The current treatment recommendation for after surgery in this patient population is platinum-based chemotherapy, which is associated with modest improvements in overall survival. But multiple trials looking at alectinib in stage I-III NSCLC are underway given the unmet need for treatment in the 4%-5% of NSCLC patients with ALK rearrangements, Dr. Solomon explained.

The ALINA trial enrolled adults with good performance status and completely resected stage IB-IIIA ALK+ NSCLC. Patients were randomized 1:1 to 600 mg of oral alectinib twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.

At median follow-up of 27.8 months, Dr. Solomon and colleagues observed an overall DFS benefit in 130 patients with stage II-IIIA disease randomized to receive alectinib, compared with the 127 patients who received chemotherapy (median DFS not reached vs. 44.4 months; hazard ratio, 0.24). The benefit was observed in the overall intention-to-treat (ITT) population of patients with stage IB-IIIA disease (median DFS not reached vs. 41.3 months; HR, 0.24).

Two-year DFS was also improved with alectinib vs. chemotherapy for stage IB (HR, 0.21), stage II (HR, 0.24), and stage IIIA disease (HR, 0.25).

The investigators observed a clinically meaningful central nervous system DFS benefit in the ITT population as well (HR, 0.22). This finding is important, given that patients with ALK+ disease have a high risk of brain metastases, which occurs in 50%-60% of patients over the course of disease, Dr. Solomon noted.

Over the treatment duration in each arm, 23.4% of patients in the alectinib arm and 25.8% in the chemotherapy arm experienced grade 3 or 4 adverse events; 5 patients in the alectinib arm and 13 in the chemotherapy arm had adverse events that led to treatment discontinuation.

“Adjuvant alectinib was tolerable and in line with the known safety profile of alectinib,” Dr. Solomon concluded, but noted that the overall survival data were not yet mature.

Invited discussant Marina Garassino, MBBS, however, cautioned against rushing to judgment, calling the DFS findings “interesting, but early.”

“Are 2 years of alectinib enough to impact overall survival? We don’t know yet,” said Dr. Garassino, professor of medicine and director of the thoracic oncology program at the University of Chicago.

Chemotherapy, conversely, has been shown to improve overall survival, she noted.

Toxicity of alectinib in the adjuvant setting may be a concern as well, she said, explaining that patients have reported numerous side effects that can affect quality of life, such as sun sensitivity, difficulty focusing, neuropathy, lower back muscle soreness, and constipation.

“So, I think we should still wait for more results from this trial,” she said.

In the meantime, she said she will ask patients “if they want this kind of toxicity in the absence of a clear overall survival benefit.”

The ALINA trial is funded by F. Hoffmann-La Roche. Dr. Solomon and Dr. Garassino each reported numerous relationships with pharmaceutical companies and other entities.

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

Alectinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, significantly improved disease-free survival (DFS) at 2 years, compared with chemotherapy, in patients with completely resected ALK+ non–small cell lung cancer (NSCLC), according to interim findings from the open-label phase 3 ALINA trial.

The results suggest that alectinib, which is currently the first-line treatment choice in more advanced NSCLC, also provides an effective new treatment strategy for patients with resected ALK+ NSCLC, said Ben Solomon, MBBS, PhD, who presented late-breaking data from the trial at the annual meeting of the European Society for Medical Oncology.

ALINA is the first phase 3 trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease, said Dr. Solomon, professor and medical oncologist at Peter MacCallum Cancer Centre, Melbourne.

The current treatment recommendation for after surgery in this patient population is platinum-based chemotherapy, which is associated with modest improvements in overall survival. But multiple trials looking at alectinib in stage I-III NSCLC are underway given the unmet need for treatment in the 4%-5% of NSCLC patients with ALK rearrangements, Dr. Solomon explained.

The ALINA trial enrolled adults with good performance status and completely resected stage IB-IIIA ALK+ NSCLC. Patients were randomized 1:1 to 600 mg of oral alectinib twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.

At median follow-up of 27.8 months, Dr. Solomon and colleagues observed an overall DFS benefit in 130 patients with stage II-IIIA disease randomized to receive alectinib, compared with the 127 patients who received chemotherapy (median DFS not reached vs. 44.4 months; hazard ratio, 0.24). The benefit was observed in the overall intention-to-treat (ITT) population of patients with stage IB-IIIA disease (median DFS not reached vs. 41.3 months; HR, 0.24).

Two-year DFS was also improved with alectinib vs. chemotherapy for stage IB (HR, 0.21), stage II (HR, 0.24), and stage IIIA disease (HR, 0.25).

The investigators observed a clinically meaningful central nervous system DFS benefit in the ITT population as well (HR, 0.22). This finding is important, given that patients with ALK+ disease have a high risk of brain metastases, which occurs in 50%-60% of patients over the course of disease, Dr. Solomon noted.

Over the treatment duration in each arm, 23.4% of patients in the alectinib arm and 25.8% in the chemotherapy arm experienced grade 3 or 4 adverse events; 5 patients in the alectinib arm and 13 in the chemotherapy arm had adverse events that led to treatment discontinuation.

“Adjuvant alectinib was tolerable and in line with the known safety profile of alectinib,” Dr. Solomon concluded, but noted that the overall survival data were not yet mature.

Invited discussant Marina Garassino, MBBS, however, cautioned against rushing to judgment, calling the DFS findings “interesting, but early.”

“Are 2 years of alectinib enough to impact overall survival? We don’t know yet,” said Dr. Garassino, professor of medicine and director of the thoracic oncology program at the University of Chicago.

Chemotherapy, conversely, has been shown to improve overall survival, she noted.

Toxicity of alectinib in the adjuvant setting may be a concern as well, she said, explaining that patients have reported numerous side effects that can affect quality of life, such as sun sensitivity, difficulty focusing, neuropathy, lower back muscle soreness, and constipation.

“So, I think we should still wait for more results from this trial,” she said.

In the meantime, she said she will ask patients “if they want this kind of toxicity in the absence of a clear overall survival benefit.”

The ALINA trial is funded by F. Hoffmann-La Roche. Dr. Solomon and Dr. Garassino each reported numerous relationships with pharmaceutical companies and other entities.

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

Alectinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, significantly improved disease-free survival (DFS) at 2 years, compared with chemotherapy, in patients with completely resected ALK+ non–small cell lung cancer (NSCLC), according to interim findings from the open-label phase 3 ALINA trial.

The results suggest that alectinib, which is currently the first-line treatment choice in more advanced NSCLC, also provides an effective new treatment strategy for patients with resected ALK+ NSCLC, said Ben Solomon, MBBS, PhD, who presented late-breaking data from the trial at the annual meeting of the European Society for Medical Oncology.

ALINA is the first phase 3 trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease, said Dr. Solomon, professor and medical oncologist at Peter MacCallum Cancer Centre, Melbourne.

The current treatment recommendation for after surgery in this patient population is platinum-based chemotherapy, which is associated with modest improvements in overall survival. But multiple trials looking at alectinib in stage I-III NSCLC are underway given the unmet need for treatment in the 4%-5% of NSCLC patients with ALK rearrangements, Dr. Solomon explained.

The ALINA trial enrolled adults with good performance status and completely resected stage IB-IIIA ALK+ NSCLC. Patients were randomized 1:1 to 600 mg of oral alectinib twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.

At median follow-up of 27.8 months, Dr. Solomon and colleagues observed an overall DFS benefit in 130 patients with stage II-IIIA disease randomized to receive alectinib, compared with the 127 patients who received chemotherapy (median DFS not reached vs. 44.4 months; hazard ratio, 0.24). The benefit was observed in the overall intention-to-treat (ITT) population of patients with stage IB-IIIA disease (median DFS not reached vs. 41.3 months; HR, 0.24).

Two-year DFS was also improved with alectinib vs. chemotherapy for stage IB (HR, 0.21), stage II (HR, 0.24), and stage IIIA disease (HR, 0.25).

The investigators observed a clinically meaningful central nervous system DFS benefit in the ITT population as well (HR, 0.22). This finding is important, given that patients with ALK+ disease have a high risk of brain metastases, which occurs in 50%-60% of patients over the course of disease, Dr. Solomon noted.

Over the treatment duration in each arm, 23.4% of patients in the alectinib arm and 25.8% in the chemotherapy arm experienced grade 3 or 4 adverse events; 5 patients in the alectinib arm and 13 in the chemotherapy arm had adverse events that led to treatment discontinuation.

“Adjuvant alectinib was tolerable and in line with the known safety profile of alectinib,” Dr. Solomon concluded, but noted that the overall survival data were not yet mature.

Invited discussant Marina Garassino, MBBS, however, cautioned against rushing to judgment, calling the DFS findings “interesting, but early.”

“Are 2 years of alectinib enough to impact overall survival? We don’t know yet,” said Dr. Garassino, professor of medicine and director of the thoracic oncology program at the University of Chicago.

Chemotherapy, conversely, has been shown to improve overall survival, she noted.

Toxicity of alectinib in the adjuvant setting may be a concern as well, she said, explaining that patients have reported numerous side effects that can affect quality of life, such as sun sensitivity, difficulty focusing, neuropathy, lower back muscle soreness, and constipation.

“So, I think we should still wait for more results from this trial,” she said.

In the meantime, she said she will ask patients “if they want this kind of toxicity in the absence of a clear overall survival benefit.”

The ALINA trial is funded by F. Hoffmann-La Roche. Dr. Solomon and Dr. Garassino each reported numerous relationships with pharmaceutical companies and other entities.

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

Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non–small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.

In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs. 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the annual meeting of the European Society for Medical Oncology.

“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer,” said Dr. Cascone, associate professor in the division of cancer medicine at University of Texas MD Anderson Cancer Center, Houston.

Invited discussant Marina Garassino, MBBS, professor of medicine and director of the thoracic oncology program at the University of Chicago, noted that the “practice-changing” CheckMate 77T findings – including the “highly statistically significant impressive hazard ratio of 0.58” – add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.

This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck’s pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.

The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.

Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7-44.2 months (not reached vs. 18.4 months; HR, 0.58; P = .00025).

The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs. stage III disease (HR, 0.81 vs. 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs. 1% or greater (HR, 0.73 vs. 0.52).

Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs. 4.7%; odds ratio, 6.64) and major pathological response (35.4% vs. 12.1%; OR, 4.01) – the trial’s secondary endpoints.

In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Dr. Cascone added.

No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.

Despite the promising findings, some questions remain, said Dr. Garassino.

First, should PD-L1–negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.

So, “the answer is yes, we should treat” these patients, she said.

But a big question is whether patients who don’t achieve a pathological complete response need adjuvant therapy. “We really don’t know,” she continued. “What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don’t achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low.”

CheckMate 77T is funded by Bristol-Myers Squibb. Dr. Cascone and Dr. Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.

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

Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non–small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.

In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs. 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the annual meeting of the European Society for Medical Oncology.

“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer,” said Dr. Cascone, associate professor in the division of cancer medicine at University of Texas MD Anderson Cancer Center, Houston.

Invited discussant Marina Garassino, MBBS, professor of medicine and director of the thoracic oncology program at the University of Chicago, noted that the “practice-changing” CheckMate 77T findings – including the “highly statistically significant impressive hazard ratio of 0.58” – add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.

This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck’s pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.

The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.

Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7-44.2 months (not reached vs. 18.4 months; HR, 0.58; P = .00025).

The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs. stage III disease (HR, 0.81 vs. 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs. 1% or greater (HR, 0.73 vs. 0.52).

Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs. 4.7%; odds ratio, 6.64) and major pathological response (35.4% vs. 12.1%; OR, 4.01) – the trial’s secondary endpoints.

In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Dr. Cascone added.

No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.

Despite the promising findings, some questions remain, said Dr. Garassino.

First, should PD-L1–negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.

So, “the answer is yes, we should treat” these patients, she said.

But a big question is whether patients who don’t achieve a pathological complete response need adjuvant therapy. “We really don’t know,” she continued. “What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don’t achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low.”

CheckMate 77T is funded by Bristol-Myers Squibb. Dr. Cascone and Dr. Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.

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

Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non–small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.

In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs. 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the annual meeting of the European Society for Medical Oncology.

“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer,” said Dr. Cascone, associate professor in the division of cancer medicine at University of Texas MD Anderson Cancer Center, Houston.

Invited discussant Marina Garassino, MBBS, professor of medicine and director of the thoracic oncology program at the University of Chicago, noted that the “practice-changing” CheckMate 77T findings – including the “highly statistically significant impressive hazard ratio of 0.58” – add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.

This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck’s pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.

The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.

Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7-44.2 months (not reached vs. 18.4 months; HR, 0.58; P = .00025).

The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs. stage III disease (HR, 0.81 vs. 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs. 1% or greater (HR, 0.73 vs. 0.52).

Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs. 4.7%; odds ratio, 6.64) and major pathological response (35.4% vs. 12.1%; OR, 4.01) – the trial’s secondary endpoints.

In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Dr. Cascone added.

No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.

Despite the promising findings, some questions remain, said Dr. Garassino.

First, should PD-L1–negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.

So, “the answer is yes, we should treat” these patients, she said.

But a big question is whether patients who don’t achieve a pathological complete response need adjuvant therapy. “We really don’t know,” she continued. “What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don’t achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low.”

CheckMate 77T is funded by Bristol-Myers Squibb. Dr. Cascone and Dr. Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.

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

Further evidence for the benefit of adding immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early high-risk estrogen receptor–positive, HER2-negative (HR+/HER2–) breast cancer comes from results of two randomized trials presented at the annual meeting of the European Society for Medical Oncology.

In the KEYNOTE-756 trial, adding pembrolizumab (Keytruda) to neoadjuvant chemotherapy resulted in an 8.5% increase in pathologic complete response (pCR) rates, compared with chemotherapy alone, regardless of the patients’ programmed death ligand-1 (PD-L1) status, reported Fatima Cardoso, MD, director of the breast unit at the Champalimaud Clinical Center in Lisbon.

In the Checkmate 7FL trial, a study bedeviled by unexpected circumstances, the addition of nivolumab (Opdivo) to neoadjuvant chemotherapy resulted in a 10.5% absolute increase in pCR rates, compared with chemotherapy alone, reported Sherene Loi, MBBS, PhD, from the Peter MacCallum Cancer Centre in Melbourne.

A new paradigm?

Taken together, the trials suggest that neoadjuvant immunotherapy has the potential to be “a new paradigm,” said ESMO invited discussant Steven RD Johnston, MD, PhD, professor of breast cancer medicine at the Royal Marsden Hospital and Institute of Cancer Research in London.

“Is the management of ER-positive breast cancer going to change with immunotherapy? Can we improve pCR rates? Yes, we can. We’ve seen a significant improvement in two separate studies, albeit the rates are only at 24%, and at this point, it’s unclear if this will translate into a better event-free survival [EFS] because we have to wait and follow the data,” he said.

The data from the two studies suggest that the patients who are likely to benefit most would be those with higher-grade tumors, luminal B subtype tumors, and, possibly, those whose tumors express higher levels of PD-L1, although the definition of PD-L1 positive depends on the assay used, he said

“I think we have to make better efforts to evaluate whether genomic or immune signatures can further define those who have most to gain, and I would urge investigators in both studies to do more digging into understanding this, because you might really enrich the patients who have the most to gain from the is approach,” Dr. Johnston said.

Checkmate 7FL details

In this prospective, randomized multicenter trial patients received four cycles of neoadjuvant paclitaxel followed by four cycles of doxorubicin and cyclophosphamide (AC) and surgery with adjuvant endocrine therapy. In arm A, 257 patients received neoadjuvant and adjuvant nivolumab. In arm B 253, patients received a nivolumab placebo in both the neoadjuvant and adjuvant settings.

Eligible patients had newly diagnosed ER+/HER2– breast cancer centrally confirmed. Patients with T1c or T2 tumors who were clinically node positive on histology and those with T3 or T4 tumors of any nodal status were eligible. Patients were required to have grade 3 histology as determined by the local pathologist, or grade 2 with low ER expression.

Patients were stratified by PD-L1 status, tumor grade, axillary nodal status and frequency of AC delivery (every 2 or 3 weeks) and were then randomized into one of the two treatment arms.

Destiny takes a hand

The protocol was changed following the approval in October 2021 of adjuvant abemaciclib in patients with high-risk ER+/HER2– disease.

“This was expected to result in a high rate of withdrawals due to safety concerns when combining a CDK4/6 inhibitor with an anti-PD-1, and this put the co-primary endpoint of EFS at risk,” Dr. Loi explained.

Therefore, the investigators amended the trial protocol to establish pCR as the sole primary endpoint and ceased accrual after 521 patients were randomized.

In addition, the primary efficacy population was modified to include 510 patients across 221 sites in 31 countries after Russian sites with a total of 11 patients closed due to Russia’s war on Ukraine.

And another hurdle, trial recruitment occurred from November 2019 through April 2022, during the COVID-19 pandemic.

Checkmate 7FL results

The pCR rate in the modified intention-to-treat (ITT) population was 24.5% for patients who received nivolumab, compared with 13.8% for patients who did not, translating in an odds ratio for benefit with the ICI of 2.05 (P = .0021),

In patients with PD-L1 expression in at least 1% of cells, a secondary endpoint, the respective pCR rates were 44.3% and 20.2%, with OR of 3.11, and a confidence interval indicating statistical significance.

Residual cancer burden (RCB) rates of 0 or 1 were also higher in the nivolumab-containing arm in both the modified ITT population (30.7% vs. 21.3%), and in the PD-L1–enriched population (54.5% vs. 26.2%).

In the safety population, which included 517 patients who received at least one dose of nivolumab or placebo, rates of overall adverse events and treatment-related adverse events were similar between the two arms, with the exception of two deaths from drug toxicity in Arm A (from pneumonitis in a patient 61 days after the last neoadjuvant cycles and hepatitis in a patient 51 days after) vs. no drug toxicity deaths reported in Arm B.

Safety of the nivolumab and neoadjuvant chemotherapy combinations was consistent with known safety profiles, with no new safety signals seen, Dr. Loi said.

KEYNOTE-756 details

The KEYNOTE-756 investigators had an easier time of it than Dr. Loi and colleagues. In fact, the trial “is the first fully accrued phase 3 immunotherapy study in high-risk, early-stage ER-positive, HER2-negative breast cancer, and it met one of its primary endpoints, pCR,” Dr. Cardoso said.

She noted that in the adaptive I-SPY2 trial, the addition of pembrolizumab to neoadjuvant chemotherapy resulted in a nearly threefold improvement in estimated pCR rates in patients with ER+/HER2– tumors, indicating that the role of immunotherapy in this population warranted further exploration.

In the placebo-controlled KEYNOTE-756 trial, treatment-naive patients with locally confirmed invasive ductal breast carcinoma with stage T1c or T2 tumors 2 cm or larger with nodal status CN1 or 2, or T3 and T4 tumors with nodal status CN0-2 were enrolled.

In most centers (Eastern Europe and China being the exceptions) patients were stratified by PD-L1 status, nodal status, anthracycline regimen chosen (AC or epirubicin-cyclophosphamide [EC]) and by degree of ER-positivity. Patients, 1,278 in total, were then randomly assigned to pembrolizumab for four cycles plus paclitaxel for 12 weeks, followed by AC or EC for four cycles plus pembrolizumab, or to the same regimen without pembrolizumab.

Following surgery, patients went on to endocrine therapy for up to 10 years, with or without 6 months of additional pembrolizumab every 6 months.

KEYNOTE-756 results

For the ITT analysis, 635 patients assigned to pembrolizumab and 643 assigned to placebo were evaluable.

At the first interim assessment, conducted at a median follow-up of 33.2 months, with the longest follow-up out to 51.8 months, the co-primary endpoint of an improvement in pCR with immunotherapy was met. The pCR rate with pembrolizumab was 24.3%, compared with 15.6% with placebo, an absolute difference of 8.5% (P = .00005).

Data for the other co-primary endpoint, EFS, were not mature at the time of data cutoff, and will be reported at a future date, Dr. Cardoso said.

An analysis of pCR rates in subgroups showed that pembrolizumab benefited most patients, with the exception of those 65 years and older, patients with Eastern Cooperative Oncology Group performance status of 1 (vs. 0), patients who received their anthracycline regimen every 2 weeks rather than every 3, and node-negative patients.

The benefit was particular pronounced among patients with less than 10% ER positivity, she pointed out.

Adverse events in the neoadjuvant phase were primarily related to chemotherapy, with no major differences between the arms, although grade 3 or greater events were slightly more frequent with pembrolizumab (52.5% vs. 46.4%), and two patients in the pembrolizumab arm died (one death was from acute myocardial infarction considered related to the long QT syndrome; cause of the other patient’s death was not specified).

Adverse events leading to discontinuation were also more common with pembrolizumab (19.1% vs. 10.1%, respectively).

Immune-mediated adverse events of any grade were also higher in the immunotherapy arm, occurring in 32.8% of patients vs. 7% of patients in the placebo arm.

There were no deaths from immune-related adverse events.

Eye on safety

In his discussion, Dr. Johnston emphasized that “it’s important in a curative population that we don’t harm patients in a setting where we have a variety of other therapies available.”

Recalling the deaths of patients in the immunotherapy arm of each trial, he commented that “deaths in early breast cancer in a treatment setting are always a disaster, and we have to make sure that we manage these adverse events as we can best, and we know how to do that now.”

Checkmate 7FL was supported by Bristol Myers Squibb. Dr. Loi reported financial and nonfinancial interests with BMS and with other companies. KEYNOTE-756 was supported by Merck Sharp & Dohme. Dr. Cardoso disclosed consulting and institutional research support from Merck and others. Dr. Johnston reported consulting or advisory roles, honoraria, and research funding from several companies, not including either BMS or Merck.

Further evidence for the benefit of adding immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early high-risk estrogen receptor–positive, HER2-negative (HR+/HER2–) breast cancer comes from results of two randomized trials presented at the annual meeting of the European Society for Medical Oncology.

In the KEYNOTE-756 trial, adding pembrolizumab (Keytruda) to neoadjuvant chemotherapy resulted in an 8.5% increase in pathologic complete response (pCR) rates, compared with chemotherapy alone, regardless of the patients’ programmed death ligand-1 (PD-L1) status, reported Fatima Cardoso, MD, director of the breast unit at the Champalimaud Clinical Center in Lisbon.

In the Checkmate 7FL trial, a study bedeviled by unexpected circumstances, the addition of nivolumab (Opdivo) to neoadjuvant chemotherapy resulted in a 10.5% absolute increase in pCR rates, compared with chemotherapy alone, reported Sherene Loi, MBBS, PhD, from the Peter MacCallum Cancer Centre in Melbourne.

A new paradigm?

Taken together, the trials suggest that neoadjuvant immunotherapy has the potential to be “a new paradigm,” said ESMO invited discussant Steven RD Johnston, MD, PhD, professor of breast cancer medicine at the Royal Marsden Hospital and Institute of Cancer Research in London.

“Is the management of ER-positive breast cancer going to change with immunotherapy? Can we improve pCR rates? Yes, we can. We’ve seen a significant improvement in two separate studies, albeit the rates are only at 24%, and at this point, it’s unclear if this will translate into a better event-free survival [EFS] because we have to wait and follow the data,” he said.

The data from the two studies suggest that the patients who are likely to benefit most would be those with higher-grade tumors, luminal B subtype tumors, and, possibly, those whose tumors express higher levels of PD-L1, although the definition of PD-L1 positive depends on the assay used, he said

“I think we have to make better efforts to evaluate whether genomic or immune signatures can further define those who have most to gain, and I would urge investigators in both studies to do more digging into understanding this, because you might really enrich the patients who have the most to gain from the is approach,” Dr. Johnston said.

Checkmate 7FL details

In this prospective, randomized multicenter trial patients received four cycles of neoadjuvant paclitaxel followed by four cycles of doxorubicin and cyclophosphamide (AC) and surgery with adjuvant endocrine therapy. In arm A, 257 patients received neoadjuvant and adjuvant nivolumab. In arm B 253, patients received a nivolumab placebo in both the neoadjuvant and adjuvant settings.

Eligible patients had newly diagnosed ER+/HER2– breast cancer centrally confirmed. Patients with T1c or T2 tumors who were clinically node positive on histology and those with T3 or T4 tumors of any nodal status were eligible. Patients were required to have grade 3 histology as determined by the local pathologist, or grade 2 with low ER expression.

Patients were stratified by PD-L1 status, tumor grade, axillary nodal status and frequency of AC delivery (every 2 or 3 weeks) and were then randomized into one of the two treatment arms.

Destiny takes a hand

The protocol was changed following the approval in October 2021 of adjuvant abemaciclib in patients with high-risk ER+/HER2– disease.

“This was expected to result in a high rate of withdrawals due to safety concerns when combining a CDK4/6 inhibitor with an anti-PD-1, and this put the co-primary endpoint of EFS at risk,” Dr. Loi explained.

Therefore, the investigators amended the trial protocol to establish pCR as the sole primary endpoint and ceased accrual after 521 patients were randomized.

In addition, the primary efficacy population was modified to include 510 patients across 221 sites in 31 countries after Russian sites with a total of 11 patients closed due to Russia’s war on Ukraine.

And another hurdle, trial recruitment occurred from November 2019 through April 2022, during the COVID-19 pandemic.

Checkmate 7FL results

The pCR rate in the modified intention-to-treat (ITT) population was 24.5% for patients who received nivolumab, compared with 13.8% for patients who did not, translating in an odds ratio for benefit with the ICI of 2.05 (P = .0021),

In patients with PD-L1 expression in at least 1% of cells, a secondary endpoint, the respective pCR rates were 44.3% and 20.2%, with OR of 3.11, and a confidence interval indicating statistical significance.

Residual cancer burden (RCB) rates of 0 or 1 were also higher in the nivolumab-containing arm in both the modified ITT population (30.7% vs. 21.3%), and in the PD-L1–enriched population (54.5% vs. 26.2%).

In the safety population, which included 517 patients who received at least one dose of nivolumab or placebo, rates of overall adverse events and treatment-related adverse events were similar between the two arms, with the exception of two deaths from drug toxicity in Arm A (from pneumonitis in a patient 61 days after the last neoadjuvant cycles and hepatitis in a patient 51 days after) vs. no drug toxicity deaths reported in Arm B.

Safety of the nivolumab and neoadjuvant chemotherapy combinations was consistent with known safety profiles, with no new safety signals seen, Dr. Loi said.

KEYNOTE-756 details

The KEYNOTE-756 investigators had an easier time of it than Dr. Loi and colleagues. In fact, the trial “is the first fully accrued phase 3 immunotherapy study in high-risk, early-stage ER-positive, HER2-negative breast cancer, and it met one of its primary endpoints, pCR,” Dr. Cardoso said.

She noted that in the adaptive I-SPY2 trial, the addition of pembrolizumab to neoadjuvant chemotherapy resulted in a nearly threefold improvement in estimated pCR rates in patients with ER+/HER2– tumors, indicating that the role of immunotherapy in this population warranted further exploration.

In the placebo-controlled KEYNOTE-756 trial, treatment-naive patients with locally confirmed invasive ductal breast carcinoma with stage T1c or T2 tumors 2 cm or larger with nodal status CN1 or 2, or T3 and T4 tumors with nodal status CN0-2 were enrolled.

In most centers (Eastern Europe and China being the exceptions) patients were stratified by PD-L1 status, nodal status, anthracycline regimen chosen (AC or epirubicin-cyclophosphamide [EC]) and by degree of ER-positivity. Patients, 1,278 in total, were then randomly assigned to pembrolizumab for four cycles plus paclitaxel for 12 weeks, followed by AC or EC for four cycles plus pembrolizumab, or to the same regimen without pembrolizumab.

Following surgery, patients went on to endocrine therapy for up to 10 years, with or without 6 months of additional pembrolizumab every 6 months.

KEYNOTE-756 results

For the ITT analysis, 635 patients assigned to pembrolizumab and 643 assigned to placebo were evaluable.

At the first interim assessment, conducted at a median follow-up of 33.2 months, with the longest follow-up out to 51.8 months, the co-primary endpoint of an improvement in pCR with immunotherapy was met. The pCR rate with pembrolizumab was 24.3%, compared with 15.6% with placebo, an absolute difference of 8.5% (P = .00005).

Data for the other co-primary endpoint, EFS, were not mature at the time of data cutoff, and will be reported at a future date, Dr. Cardoso said.

An analysis of pCR rates in subgroups showed that pembrolizumab benefited most patients, with the exception of those 65 years and older, patients with Eastern Cooperative Oncology Group performance status of 1 (vs. 0), patients who received their anthracycline regimen every 2 weeks rather than every 3, and node-negative patients.

The benefit was particular pronounced among patients with less than 10% ER positivity, she pointed out.

Adverse events in the neoadjuvant phase were primarily related to chemotherapy, with no major differences between the arms, although grade 3 or greater events were slightly more frequent with pembrolizumab (52.5% vs. 46.4%), and two patients in the pembrolizumab arm died (one death was from acute myocardial infarction considered related to the long QT syndrome; cause of the other patient’s death was not specified).

Adverse events leading to discontinuation were also more common with pembrolizumab (19.1% vs. 10.1%, respectively).

Immune-mediated adverse events of any grade were also higher in the immunotherapy arm, occurring in 32.8% of patients vs. 7% of patients in the placebo arm.

There were no deaths from immune-related adverse events.

Eye on safety

In his discussion, Dr. Johnston emphasized that “it’s important in a curative population that we don’t harm patients in a setting where we have a variety of other therapies available.”

Recalling the deaths of patients in the immunotherapy arm of each trial, he commented that “deaths in early breast cancer in a treatment setting are always a disaster, and we have to make sure that we manage these adverse events as we can best, and we know how to do that now.”

Checkmate 7FL was supported by Bristol Myers Squibb. Dr. Loi reported financial and nonfinancial interests with BMS and with other companies. KEYNOTE-756 was supported by Merck Sharp & Dohme. Dr. Cardoso disclosed consulting and institutional research support from Merck and others. Dr. Johnston reported consulting or advisory roles, honoraria, and research funding from several companies, not including either BMS or Merck.

Further evidence for the benefit of adding immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early high-risk estrogen receptor–positive, HER2-negative (HR+/HER2–) breast cancer comes from results of two randomized trials presented at the annual meeting of the European Society for Medical Oncology.

In the KEYNOTE-756 trial, adding pembrolizumab (Keytruda) to neoadjuvant chemotherapy resulted in an 8.5% increase in pathologic complete response (pCR) rates, compared with chemotherapy alone, regardless of the patients’ programmed death ligand-1 (PD-L1) status, reported Fatima Cardoso, MD, director of the breast unit at the Champalimaud Clinical Center in Lisbon.

In the Checkmate 7FL trial, a study bedeviled by unexpected circumstances, the addition of nivolumab (Opdivo) to neoadjuvant chemotherapy resulted in a 10.5% absolute increase in pCR rates, compared with chemotherapy alone, reported Sherene Loi, MBBS, PhD, from the Peter MacCallum Cancer Centre in Melbourne.

A new paradigm?

Taken together, the trials suggest that neoadjuvant immunotherapy has the potential to be “a new paradigm,” said ESMO invited discussant Steven RD Johnston, MD, PhD, professor of breast cancer medicine at the Royal Marsden Hospital and Institute of Cancer Research in London.

“Is the management of ER-positive breast cancer going to change with immunotherapy? Can we improve pCR rates? Yes, we can. We’ve seen a significant improvement in two separate studies, albeit the rates are only at 24%, and at this point, it’s unclear if this will translate into a better event-free survival [EFS] because we have to wait and follow the data,” he said.

The data from the two studies suggest that the patients who are likely to benefit most would be those with higher-grade tumors, luminal B subtype tumors, and, possibly, those whose tumors express higher levels of PD-L1, although the definition of PD-L1 positive depends on the assay used, he said

“I think we have to make better efforts to evaluate whether genomic or immune signatures can further define those who have most to gain, and I would urge investigators in both studies to do more digging into understanding this, because you might really enrich the patients who have the most to gain from the is approach,” Dr. Johnston said.

Checkmate 7FL details

In this prospective, randomized multicenter trial patients received four cycles of neoadjuvant paclitaxel followed by four cycles of doxorubicin and cyclophosphamide (AC) and surgery with adjuvant endocrine therapy. In arm A, 257 patients received neoadjuvant and adjuvant nivolumab. In arm B 253, patients received a nivolumab placebo in both the neoadjuvant and adjuvant settings.

Eligible patients had newly diagnosed ER+/HER2– breast cancer centrally confirmed. Patients with T1c or T2 tumors who were clinically node positive on histology and those with T3 or T4 tumors of any nodal status were eligible. Patients were required to have grade 3 histology as determined by the local pathologist, or grade 2 with low ER expression.

Patients were stratified by PD-L1 status, tumor grade, axillary nodal status and frequency of AC delivery (every 2 or 3 weeks) and were then randomized into one of the two treatment arms.

Destiny takes a hand

The protocol was changed following the approval in October 2021 of adjuvant abemaciclib in patients with high-risk ER+/HER2– disease.

“This was expected to result in a high rate of withdrawals due to safety concerns when combining a CDK4/6 inhibitor with an anti-PD-1, and this put the co-primary endpoint of EFS at risk,” Dr. Loi explained.

Therefore, the investigators amended the trial protocol to establish pCR as the sole primary endpoint and ceased accrual after 521 patients were randomized.

In addition, the primary efficacy population was modified to include 510 patients across 221 sites in 31 countries after Russian sites with a total of 11 patients closed due to Russia’s war on Ukraine.

And another hurdle, trial recruitment occurred from November 2019 through April 2022, during the COVID-19 pandemic.

Checkmate 7FL results

The pCR rate in the modified intention-to-treat (ITT) population was 24.5% for patients who received nivolumab, compared with 13.8% for patients who did not, translating in an odds ratio for benefit with the ICI of 2.05 (P = .0021),

In patients with PD-L1 expression in at least 1% of cells, a secondary endpoint, the respective pCR rates were 44.3% and 20.2%, with OR of 3.11, and a confidence interval indicating statistical significance.

Residual cancer burden (RCB) rates of 0 or 1 were also higher in the nivolumab-containing arm in both the modified ITT population (30.7% vs. 21.3%), and in the PD-L1–enriched population (54.5% vs. 26.2%).

In the safety population, which included 517 patients who received at least one dose of nivolumab or placebo, rates of overall adverse events and treatment-related adverse events were similar between the two arms, with the exception of two deaths from drug toxicity in Arm A (from pneumonitis in a patient 61 days after the last neoadjuvant cycles and hepatitis in a patient 51 days after) vs. no drug toxicity deaths reported in Arm B.

Safety of the nivolumab and neoadjuvant chemotherapy combinations was consistent with known safety profiles, with no new safety signals seen, Dr. Loi said.

KEYNOTE-756 details

The KEYNOTE-756 investigators had an easier time of it than Dr. Loi and colleagues. In fact, the trial “is the first fully accrued phase 3 immunotherapy study in high-risk, early-stage ER-positive, HER2-negative breast cancer, and it met one of its primary endpoints, pCR,” Dr. Cardoso said.

She noted that in the adaptive I-SPY2 trial, the addition of pembrolizumab to neoadjuvant chemotherapy resulted in a nearly threefold improvement in estimated pCR rates in patients with ER+/HER2– tumors, indicating that the role of immunotherapy in this population warranted further exploration.

In the placebo-controlled KEYNOTE-756 trial, treatment-naive patients with locally confirmed invasive ductal breast carcinoma with stage T1c or T2 tumors 2 cm or larger with nodal status CN1 or 2, or T3 and T4 tumors with nodal status CN0-2 were enrolled.

In most centers (Eastern Europe and China being the exceptions) patients were stratified by PD-L1 status, nodal status, anthracycline regimen chosen (AC or epirubicin-cyclophosphamide [EC]) and by degree of ER-positivity. Patients, 1,278 in total, were then randomly assigned to pembrolizumab for four cycles plus paclitaxel for 12 weeks, followed by AC or EC for four cycles plus pembrolizumab, or to the same regimen without pembrolizumab.

Following surgery, patients went on to endocrine therapy for up to 10 years, with or without 6 months of additional pembrolizumab every 6 months.

KEYNOTE-756 results

For the ITT analysis, 635 patients assigned to pembrolizumab and 643 assigned to placebo were evaluable.

At the first interim assessment, conducted at a median follow-up of 33.2 months, with the longest follow-up out to 51.8 months, the co-primary endpoint of an improvement in pCR with immunotherapy was met. The pCR rate with pembrolizumab was 24.3%, compared with 15.6% with placebo, an absolute difference of 8.5% (P = .00005).

Data for the other co-primary endpoint, EFS, were not mature at the time of data cutoff, and will be reported at a future date, Dr. Cardoso said.

An analysis of pCR rates in subgroups showed that pembrolizumab benefited most patients, with the exception of those 65 years and older, patients with Eastern Cooperative Oncology Group performance status of 1 (vs. 0), patients who received their anthracycline regimen every 2 weeks rather than every 3, and node-negative patients.

The benefit was particular pronounced among patients with less than 10% ER positivity, she pointed out.

Adverse events in the neoadjuvant phase were primarily related to chemotherapy, with no major differences between the arms, although grade 3 or greater events were slightly more frequent with pembrolizumab (52.5% vs. 46.4%), and two patients in the pembrolizumab arm died (one death was from acute myocardial infarction considered related to the long QT syndrome; cause of the other patient’s death was not specified).

Adverse events leading to discontinuation were also more common with pembrolizumab (19.1% vs. 10.1%, respectively).

Immune-mediated adverse events of any grade were also higher in the immunotherapy arm, occurring in 32.8% of patients vs. 7% of patients in the placebo arm.

There were no deaths from immune-related adverse events.

Eye on safety

In his discussion, Dr. Johnston emphasized that “it’s important in a curative population that we don’t harm patients in a setting where we have a variety of other therapies available.”

Recalling the deaths of patients in the immunotherapy arm of each trial, he commented that “deaths in early breast cancer in a treatment setting are always a disaster, and we have to make sure that we manage these adverse events as we can best, and we know how to do that now.”

Checkmate 7FL was supported by Bristol Myers Squibb. Dr. Loi reported financial and nonfinancial interests with BMS and with other companies. KEYNOTE-756 was supported by Merck Sharp & Dohme. Dr. Cardoso disclosed consulting and institutional research support from Merck and others. Dr. Johnston reported consulting or advisory roles, honoraria, and research funding from several companies, not including either BMS or Merck.

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.