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Tarlatamab Shows Promise in Tackling Previously Treated SCLC
The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.
Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
The research was presented at the European Lung Cancer Congress 2024 on March 22.
Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.
The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.
At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.
The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.
Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.
The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.
Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.
Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.
In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.
No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome.
Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall.
“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.
And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”
On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.
“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.
DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
A version of this article appeared on Medscape.com.
The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.
Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
The research was presented at the European Lung Cancer Congress 2024 on March 22.
Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.
The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.
At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.
The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.
Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.
The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.
Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.
Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.
In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.
No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome.
Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall.
“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.
And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”
On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.
“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.
DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
A version of this article appeared on Medscape.com.
The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.
Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
The research was presented at the European Lung Cancer Congress 2024 on March 22.
Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.
The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.
At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.
The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.
Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.
The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.
Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.
Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.
In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.
No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome.
Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall.
“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.
And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”
On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.
“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.
DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
A version of this article appeared on Medscape.com.
FROM ELCC 2024
Debate: Does ctDNA Have Role in Monitoring Tx Efficacy in Lung Cancer?
The clinical utility of circulating tumor DNA (ctDNA) for detecting minimal residual disease (MRD) and for treatment planning postoperatively was a topic of debate at the European Lung Cancer Congress 2024, held in Prague, Czech Republic.
PRO: Prognostic Value
Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, argued in favor of using liquid biopsy for disease surveillance and decision making about adjuvant therapy.
“In early stage non–small cell lung cancer I think the evidence shows that pretreatment baseline ctDNA levels are clearly prognostic, and also, after surgical resection, the MRD predicts relapse, so we know that at present ctDNA and MRD are strong prognostic markers,” she said.
“I think ctDNA is useful as a noninvasive tool in both settings — at baseline pre surgery and also post surgery — to guide adjuvant therapy decision making,” she added.
Dr. Felip noted that so-called “tumor-informed” assays, such as sequencing of tumor tissue to identify mutations that can then be tracked in plasma samples, are high sensitivity methods, but have a long turnaround time, and approximately one in five patients does not have adequate tumor tissues for analysis.
In contrast, “tumor agnostic” methods rely on epigenetic features such as DNA methylation and cell-free DNA fragmentation patterns to detect tumor-derived DNA, but don’t rely on tumor tissue sample.
Dr. Felip cited a 2017 study published in Cancer Discovery showing that in patients with localized lung cancer post treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months. In addition, the investigators found that 53% of patients had ctDNA mutation profiles that suggested they would respond favorably to tyrosine kinase inhibitors or immune checkpoint inhibitors.
She also pointed to 2022 European Society for Medical Oncology (ESMO) recommendations on the use of ctDNA in patients with cancer, which state that detection of residual tumor DNA after NSCLC therapy with curative intent is associated with a high risk of future relapse, as supported by evidence from multiple studies. The recommendation also states, however, that there is insufficient evidence to recommend ctDNA testing in routine clinical practice in the absence of evidence from prospective clinical trials.
Evidence to support a benefit of ctDNA detection for treatment planning in the adjuvant setting come from several clinical studies, Dr. Felip said. For example, in a 2020 study published in Nature Cancer, investigators found that patients with detectable ctDNA after chemoradiotherapy who had treatment consolidation with an immune checkpoint inhibitor had significantly better freedom from progression compared with patients who had detectable ctDNA but did not receive consolidation immunotherapy.
In the IMpower010 trial, patients who were ctDNA-positive post surgery and received adjuvant atezolizumab (Tecentriq) had a median disease-free survival of 19.1 months, compared with 7.9 months for patients who did not get the immune checkpoint inhibitor, further indicating the value of ctDNA in the adjuvant setting, she said.
Wrapping up her argument, Dr. Felip acknowledged that currently the negative predictive value of ctDNA/MRD is suboptimal.
“However, we have seen that high ctDNA levels pre surgery predict poor outcome, and MRD-positive following definitive therapy is strongly prognostic and has extremely high positive predictive value for recurrence,” she said.
Taken together, the evidence suggests that patients who are ctDNA-positive preoperatively should be considered for neoadjuvant chemotherapy and immune checkpoint inhibition. If ctDNA persists after neoadjuvant therapy, patients should have extensive re-staging before surgery, because their options for pathologic complete response are limited. Patients who are MRD-positive after surgery should be treated with the same therapeutic approach as for patients with metastatic disease, Dr. Felip concluded.
CON: No Data Supporting OS Benefit
Offering counterpoint to Dr. Felip’s argument, Jordi Remon Masip, MD, PhD, of Gustave Roussy cancer treatment center in Villejuif, France, said that the currently available evidence suggests that MRD helps identify a high-risk population, but that its utility in the clinic is still uncertain.
“Today, I am a believer that we need prospective clinical trials, but one of the most important points today is to elucidate if the minimal residual disease is just prognostic or whether we really can use this minimal residual disease for making treatment decisions, not only escalating [but] also de-escalating treatment strategies in early stage non–small cell lung cancer,” he said.
Risk stratification may help to identify those patients who can most benefit from intensive therapy, but it appears to be much more difficult to risk stratify patients with early stage NSCLC, he said, pointing to the International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in patients with completely resected stage II-IIIA NSCLC. In this study, chemotherapy customized to individual patients according to molecular diagnostic analysis after surgery did not improve overall survival outcomes.
Dr. Masip said that as a clinician he would like to have any reliable tool that could help him to decide which patients need more therapy and which can do well with less.
He agreed that MRD-positivity as signaled by ctDNA after surgery or by a tumor-informed method correlates with poor prognosis, but he noted that MRD status depends on clinical characteristics such as sex, smoking status, age, stage, tumor size, histology, and many other factors that need to be taken into account if the assay is to have value in clinical practice.
“It’s true that the minimal residual disease may capture a poor prognostic population. However, even if we apply the minimal residual disease in our daily clinical practice, we can only capture, or we can only rescue 20% of the patients with the wild type or oncogenic early stage non–small cell lung cancer,” he said.
In addition, as Dr. Felip acknowledged, the negative predictive value of MRD is not infallible, with a 63% false negative rate compared with only a 2% false-positive rate.
“Half of the patients with the recurrence of the disease have a very, very low circulating tumor DNA, and the techniques are not sensitive enough to capture this minimal residual disease,” Dr. Masip said.
It would also be a mistake to forgo giving adjuvant therapy to those patients deemed to be MRD-negative on the basis of ctDNA, given the high false-negative rates, he said.
Oncologists also have to put themselves in their patients’ shoes:
“If our patients accept that with minimal residual disease I can only improve the disease-free survival without improving the overall survival, they would accept having less toxicity but the same survival that they would if they started the treatment later, and also what would happen if the patient is randomized to no adjuvant treatment because the minimal residual disease is negative, and some months later there is a recurrence of disease?” Dr. Masip said.
“I think we need more prospective data, but we really, really need a more sensitive test to avoid or to decrease the percentage of patients with false-negative results, and also we need very motivated patients that would accept to be randomized to de-escalate treatment strategies,” he concluded.
Dr. Felip disclosed advisory or speakers bureau roles for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics. She has served as a board member of Grifols. Dr. Masip disclosed research support from MSD, AstraZeneca, and Sanofi, and other financial relationships with AstraZeneca, Sanofi, Takeda Roche, and Janssen.
The clinical utility of circulating tumor DNA (ctDNA) for detecting minimal residual disease (MRD) and for treatment planning postoperatively was a topic of debate at the European Lung Cancer Congress 2024, held in Prague, Czech Republic.
PRO: Prognostic Value
Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, argued in favor of using liquid biopsy for disease surveillance and decision making about adjuvant therapy.
“In early stage non–small cell lung cancer I think the evidence shows that pretreatment baseline ctDNA levels are clearly prognostic, and also, after surgical resection, the MRD predicts relapse, so we know that at present ctDNA and MRD are strong prognostic markers,” she said.
“I think ctDNA is useful as a noninvasive tool in both settings — at baseline pre surgery and also post surgery — to guide adjuvant therapy decision making,” she added.
Dr. Felip noted that so-called “tumor-informed” assays, such as sequencing of tumor tissue to identify mutations that can then be tracked in plasma samples, are high sensitivity methods, but have a long turnaround time, and approximately one in five patients does not have adequate tumor tissues for analysis.
In contrast, “tumor agnostic” methods rely on epigenetic features such as DNA methylation and cell-free DNA fragmentation patterns to detect tumor-derived DNA, but don’t rely on tumor tissue sample.
Dr. Felip cited a 2017 study published in Cancer Discovery showing that in patients with localized lung cancer post treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months. In addition, the investigators found that 53% of patients had ctDNA mutation profiles that suggested they would respond favorably to tyrosine kinase inhibitors or immune checkpoint inhibitors.
She also pointed to 2022 European Society for Medical Oncology (ESMO) recommendations on the use of ctDNA in patients with cancer, which state that detection of residual tumor DNA after NSCLC therapy with curative intent is associated with a high risk of future relapse, as supported by evidence from multiple studies. The recommendation also states, however, that there is insufficient evidence to recommend ctDNA testing in routine clinical practice in the absence of evidence from prospective clinical trials.
Evidence to support a benefit of ctDNA detection for treatment planning in the adjuvant setting come from several clinical studies, Dr. Felip said. For example, in a 2020 study published in Nature Cancer, investigators found that patients with detectable ctDNA after chemoradiotherapy who had treatment consolidation with an immune checkpoint inhibitor had significantly better freedom from progression compared with patients who had detectable ctDNA but did not receive consolidation immunotherapy.
In the IMpower010 trial, patients who were ctDNA-positive post surgery and received adjuvant atezolizumab (Tecentriq) had a median disease-free survival of 19.1 months, compared with 7.9 months for patients who did not get the immune checkpoint inhibitor, further indicating the value of ctDNA in the adjuvant setting, she said.
Wrapping up her argument, Dr. Felip acknowledged that currently the negative predictive value of ctDNA/MRD is suboptimal.
“However, we have seen that high ctDNA levels pre surgery predict poor outcome, and MRD-positive following definitive therapy is strongly prognostic and has extremely high positive predictive value for recurrence,” she said.
Taken together, the evidence suggests that patients who are ctDNA-positive preoperatively should be considered for neoadjuvant chemotherapy and immune checkpoint inhibition. If ctDNA persists after neoadjuvant therapy, patients should have extensive re-staging before surgery, because their options for pathologic complete response are limited. Patients who are MRD-positive after surgery should be treated with the same therapeutic approach as for patients with metastatic disease, Dr. Felip concluded.
CON: No Data Supporting OS Benefit
Offering counterpoint to Dr. Felip’s argument, Jordi Remon Masip, MD, PhD, of Gustave Roussy cancer treatment center in Villejuif, France, said that the currently available evidence suggests that MRD helps identify a high-risk population, but that its utility in the clinic is still uncertain.
“Today, I am a believer that we need prospective clinical trials, but one of the most important points today is to elucidate if the minimal residual disease is just prognostic or whether we really can use this minimal residual disease for making treatment decisions, not only escalating [but] also de-escalating treatment strategies in early stage non–small cell lung cancer,” he said.
Risk stratification may help to identify those patients who can most benefit from intensive therapy, but it appears to be much more difficult to risk stratify patients with early stage NSCLC, he said, pointing to the International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in patients with completely resected stage II-IIIA NSCLC. In this study, chemotherapy customized to individual patients according to molecular diagnostic analysis after surgery did not improve overall survival outcomes.
Dr. Masip said that as a clinician he would like to have any reliable tool that could help him to decide which patients need more therapy and which can do well with less.
He agreed that MRD-positivity as signaled by ctDNA after surgery or by a tumor-informed method correlates with poor prognosis, but he noted that MRD status depends on clinical characteristics such as sex, smoking status, age, stage, tumor size, histology, and many other factors that need to be taken into account if the assay is to have value in clinical practice.
“It’s true that the minimal residual disease may capture a poor prognostic population. However, even if we apply the minimal residual disease in our daily clinical practice, we can only capture, or we can only rescue 20% of the patients with the wild type or oncogenic early stage non–small cell lung cancer,” he said.
In addition, as Dr. Felip acknowledged, the negative predictive value of MRD is not infallible, with a 63% false negative rate compared with only a 2% false-positive rate.
“Half of the patients with the recurrence of the disease have a very, very low circulating tumor DNA, and the techniques are not sensitive enough to capture this minimal residual disease,” Dr. Masip said.
It would also be a mistake to forgo giving adjuvant therapy to those patients deemed to be MRD-negative on the basis of ctDNA, given the high false-negative rates, he said.
Oncologists also have to put themselves in their patients’ shoes:
“If our patients accept that with minimal residual disease I can only improve the disease-free survival without improving the overall survival, they would accept having less toxicity but the same survival that they would if they started the treatment later, and also what would happen if the patient is randomized to no adjuvant treatment because the minimal residual disease is negative, and some months later there is a recurrence of disease?” Dr. Masip said.
“I think we need more prospective data, but we really, really need a more sensitive test to avoid or to decrease the percentage of patients with false-negative results, and also we need very motivated patients that would accept to be randomized to de-escalate treatment strategies,” he concluded.
Dr. Felip disclosed advisory or speakers bureau roles for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics. She has served as a board member of Grifols. Dr. Masip disclosed research support from MSD, AstraZeneca, and Sanofi, and other financial relationships with AstraZeneca, Sanofi, Takeda Roche, and Janssen.
The clinical utility of circulating tumor DNA (ctDNA) for detecting minimal residual disease (MRD) and for treatment planning postoperatively was a topic of debate at the European Lung Cancer Congress 2024, held in Prague, Czech Republic.
PRO: Prognostic Value
Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, argued in favor of using liquid biopsy for disease surveillance and decision making about adjuvant therapy.
“In early stage non–small cell lung cancer I think the evidence shows that pretreatment baseline ctDNA levels are clearly prognostic, and also, after surgical resection, the MRD predicts relapse, so we know that at present ctDNA and MRD are strong prognostic markers,” she said.
“I think ctDNA is useful as a noninvasive tool in both settings — at baseline pre surgery and also post surgery — to guide adjuvant therapy decision making,” she added.
Dr. Felip noted that so-called “tumor-informed” assays, such as sequencing of tumor tissue to identify mutations that can then be tracked in plasma samples, are high sensitivity methods, but have a long turnaround time, and approximately one in five patients does not have adequate tumor tissues for analysis.
In contrast, “tumor agnostic” methods rely on epigenetic features such as DNA methylation and cell-free DNA fragmentation patterns to detect tumor-derived DNA, but don’t rely on tumor tissue sample.
Dr. Felip cited a 2017 study published in Cancer Discovery showing that in patients with localized lung cancer post treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months. In addition, the investigators found that 53% of patients had ctDNA mutation profiles that suggested they would respond favorably to tyrosine kinase inhibitors or immune checkpoint inhibitors.
She also pointed to 2022 European Society for Medical Oncology (ESMO) recommendations on the use of ctDNA in patients with cancer, which state that detection of residual tumor DNA after NSCLC therapy with curative intent is associated with a high risk of future relapse, as supported by evidence from multiple studies. The recommendation also states, however, that there is insufficient evidence to recommend ctDNA testing in routine clinical practice in the absence of evidence from prospective clinical trials.
Evidence to support a benefit of ctDNA detection for treatment planning in the adjuvant setting come from several clinical studies, Dr. Felip said. For example, in a 2020 study published in Nature Cancer, investigators found that patients with detectable ctDNA after chemoradiotherapy who had treatment consolidation with an immune checkpoint inhibitor had significantly better freedom from progression compared with patients who had detectable ctDNA but did not receive consolidation immunotherapy.
In the IMpower010 trial, patients who were ctDNA-positive post surgery and received adjuvant atezolizumab (Tecentriq) had a median disease-free survival of 19.1 months, compared with 7.9 months for patients who did not get the immune checkpoint inhibitor, further indicating the value of ctDNA in the adjuvant setting, she said.
Wrapping up her argument, Dr. Felip acknowledged that currently the negative predictive value of ctDNA/MRD is suboptimal.
“However, we have seen that high ctDNA levels pre surgery predict poor outcome, and MRD-positive following definitive therapy is strongly prognostic and has extremely high positive predictive value for recurrence,” she said.
Taken together, the evidence suggests that patients who are ctDNA-positive preoperatively should be considered for neoadjuvant chemotherapy and immune checkpoint inhibition. If ctDNA persists after neoadjuvant therapy, patients should have extensive re-staging before surgery, because their options for pathologic complete response are limited. Patients who are MRD-positive after surgery should be treated with the same therapeutic approach as for patients with metastatic disease, Dr. Felip concluded.
CON: No Data Supporting OS Benefit
Offering counterpoint to Dr. Felip’s argument, Jordi Remon Masip, MD, PhD, of Gustave Roussy cancer treatment center in Villejuif, France, said that the currently available evidence suggests that MRD helps identify a high-risk population, but that its utility in the clinic is still uncertain.
“Today, I am a believer that we need prospective clinical trials, but one of the most important points today is to elucidate if the minimal residual disease is just prognostic or whether we really can use this minimal residual disease for making treatment decisions, not only escalating [but] also de-escalating treatment strategies in early stage non–small cell lung cancer,” he said.
Risk stratification may help to identify those patients who can most benefit from intensive therapy, but it appears to be much more difficult to risk stratify patients with early stage NSCLC, he said, pointing to the International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in patients with completely resected stage II-IIIA NSCLC. In this study, chemotherapy customized to individual patients according to molecular diagnostic analysis after surgery did not improve overall survival outcomes.
Dr. Masip said that as a clinician he would like to have any reliable tool that could help him to decide which patients need more therapy and which can do well with less.
He agreed that MRD-positivity as signaled by ctDNA after surgery or by a tumor-informed method correlates with poor prognosis, but he noted that MRD status depends on clinical characteristics such as sex, smoking status, age, stage, tumor size, histology, and many other factors that need to be taken into account if the assay is to have value in clinical practice.
“It’s true that the minimal residual disease may capture a poor prognostic population. However, even if we apply the minimal residual disease in our daily clinical practice, we can only capture, or we can only rescue 20% of the patients with the wild type or oncogenic early stage non–small cell lung cancer,” he said.
In addition, as Dr. Felip acknowledged, the negative predictive value of MRD is not infallible, with a 63% false negative rate compared with only a 2% false-positive rate.
“Half of the patients with the recurrence of the disease have a very, very low circulating tumor DNA, and the techniques are not sensitive enough to capture this minimal residual disease,” Dr. Masip said.
It would also be a mistake to forgo giving adjuvant therapy to those patients deemed to be MRD-negative on the basis of ctDNA, given the high false-negative rates, he said.
Oncologists also have to put themselves in their patients’ shoes:
“If our patients accept that with minimal residual disease I can only improve the disease-free survival without improving the overall survival, they would accept having less toxicity but the same survival that they would if they started the treatment later, and also what would happen if the patient is randomized to no adjuvant treatment because the minimal residual disease is negative, and some months later there is a recurrence of disease?” Dr. Masip said.
“I think we need more prospective data, but we really, really need a more sensitive test to avoid or to decrease the percentage of patients with false-negative results, and also we need very motivated patients that would accept to be randomized to de-escalate treatment strategies,” he concluded.
Dr. Felip disclosed advisory or speakers bureau roles for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics. She has served as a board member of Grifols. Dr. Masip disclosed research support from MSD, AstraZeneca, and Sanofi, and other financial relationships with AstraZeneca, Sanofi, Takeda Roche, and Janssen.
FROM ELCC 2024
Savolitinib Active Against MET Ex14 Mutated NSCLC
Savolitinib, a selective oral tyrosine kinase inhibitor, showed good activity against locally advanced or metastatic non–small cell lung cancer (NSCLC) bearing MET exon 14 mutations as both first-line therapy for treatment-naive patients and in second-line of therapy for previously treated patients
“The phase 3b study results further confirm savolitinib as a valuable targeted therapy option for naive and previously-treated non–small cell lung cancer with MET 14 exon mutations,” Yongchang Zhang, MD, said while presenting the final results of the trial at the European Lung Cancer Congress 2024.
For 87 previously untreated patients the objective response rate (ORR) as assessed by independent review, the primary endpoint, was 62.1%. For 79 patients receiving savolitinib in the second line, the ORR was 39.2%, reported Dr. Zhang, MD, of the Hunan Cancer Hospital in Changsha, China.
Preliminary results of this trial were reported at the World Conference on Lung Cancer in 2023.
Selective Inhibitor
Savolitinib (AZD6094, also called volitinib) is reported to be a highly selective oral inhibitor of the MET receptor tyrosine kinase (TKI). It is approved in China for the treatment of patients with NSCLC harboring MET exon 14 mutations that has progressed on prior systemic therapy, or patients who are unable to tolerate platinum-based chemotherapy.
In the phase 3b study, patients with MET ex14-positive tumors who were negative for EGFR, ALK or ROS1 alterations and were naive to a MET inhibitor were enrolled. Those who weighed 50 kg or greater received 600 mg savolitinib orally once daily for each 21-day cycle, while patients who weighed less than 50 kg received a 400-mg daily dose. Therapy continued until disease progression, death, or unacceptable toxicity.
Tumors were evaluated by investigators every 6 weeks for the first year, than every 12 weeks thereafter.
As noted before, ORR by independent review was 62.1% for treatment-naive patients and 39.2% for previously treated patients. The respective ORRs by investigator assessment were 59.8% and 43%. All responses in each arm were partial responses.
Median progression-free survival (PFS) after a median follow-up of 18 months for treatment-naive patients and 11 months for treatment-experienced patients was 13.7 months and 11 months, respectively.
Overall survival after a median follow-up of 20.8 months for treatment-naive patients and 12.5 months for previously treated patients was not reached in treatment-naive patients and not mature in treatment-experienced patients.
Grade 3 or greater treatment-emergent adverse events occurred in 74.1% of patients, including 3 events (1.8%) leading to death. Dose modifications were required for 74.7% of patients.
Grade 3 or greater adverse events included peripheral edema, liver enzyme elevations, abnormal liver function, decreased platelet and white blood cell counts, and vomiting.
Which TKI is Best?
Invited discussant Antonio Passaro, MD, PhD, from the European Institute of Oncology in Milan, noted that eligibility for treatment with savolitinib or other MET exon 14-targeting TKIs is limited to about 3% of patients with NSCLC of adenocarcinoma histology.
He said that savolitinib appears to be similar in performance to two other TKIs for NSCLC with MET exon-14 skipping mutations that are currently on the market in the United States, Europe, and Japan: capmatinib (Tabrecta) and tepotinib (Tepmetko).
“Globally, all the results show a numerically better performance when we use a selective TKI in first-line treatment over the second-line treatment, in particular for overall response rate,” he said.
Dr. Passaro noted that savolitinib differs from the other two MET TKIs in that PFS with savolitinib is similar for treatment-naive and previously treated patients.
He added, however, that “today it’s very difficult” to determine which is the “perfect” agent for a specific disease presentation, particularly since MET exon 14 skipping mutations can also be found in patients with squamous cell carcinomas and those with a history of smoking.
To get a better sense of which drug to use in a specific situation, it would be helpful to analyze trial results in the context of tumor histology, smoking history, programmed death protein 1-ligand 1 status, and co-mutations, he said.
The study was sponsored by Hutchmed. Dr. Zhang reported having no conflicts of interest. Dr. Passaro reported a consulting, advisory, or speakers bureau role for multiple companies, not including Hutchmed.
Savolitinib, a selective oral tyrosine kinase inhibitor, showed good activity against locally advanced or metastatic non–small cell lung cancer (NSCLC) bearing MET exon 14 mutations as both first-line therapy for treatment-naive patients and in second-line of therapy for previously treated patients
“The phase 3b study results further confirm savolitinib as a valuable targeted therapy option for naive and previously-treated non–small cell lung cancer with MET 14 exon mutations,” Yongchang Zhang, MD, said while presenting the final results of the trial at the European Lung Cancer Congress 2024.
For 87 previously untreated patients the objective response rate (ORR) as assessed by independent review, the primary endpoint, was 62.1%. For 79 patients receiving savolitinib in the second line, the ORR was 39.2%, reported Dr. Zhang, MD, of the Hunan Cancer Hospital in Changsha, China.
Preliminary results of this trial were reported at the World Conference on Lung Cancer in 2023.
Selective Inhibitor
Savolitinib (AZD6094, also called volitinib) is reported to be a highly selective oral inhibitor of the MET receptor tyrosine kinase (TKI). It is approved in China for the treatment of patients with NSCLC harboring MET exon 14 mutations that has progressed on prior systemic therapy, or patients who are unable to tolerate platinum-based chemotherapy.
In the phase 3b study, patients with MET ex14-positive tumors who were negative for EGFR, ALK or ROS1 alterations and were naive to a MET inhibitor were enrolled. Those who weighed 50 kg or greater received 600 mg savolitinib orally once daily for each 21-day cycle, while patients who weighed less than 50 kg received a 400-mg daily dose. Therapy continued until disease progression, death, or unacceptable toxicity.
Tumors were evaluated by investigators every 6 weeks for the first year, than every 12 weeks thereafter.
As noted before, ORR by independent review was 62.1% for treatment-naive patients and 39.2% for previously treated patients. The respective ORRs by investigator assessment were 59.8% and 43%. All responses in each arm were partial responses.
Median progression-free survival (PFS) after a median follow-up of 18 months for treatment-naive patients and 11 months for treatment-experienced patients was 13.7 months and 11 months, respectively.
Overall survival after a median follow-up of 20.8 months for treatment-naive patients and 12.5 months for previously treated patients was not reached in treatment-naive patients and not mature in treatment-experienced patients.
Grade 3 or greater treatment-emergent adverse events occurred in 74.1% of patients, including 3 events (1.8%) leading to death. Dose modifications were required for 74.7% of patients.
Grade 3 or greater adverse events included peripheral edema, liver enzyme elevations, abnormal liver function, decreased platelet and white blood cell counts, and vomiting.
Which TKI is Best?
Invited discussant Antonio Passaro, MD, PhD, from the European Institute of Oncology in Milan, noted that eligibility for treatment with savolitinib or other MET exon 14-targeting TKIs is limited to about 3% of patients with NSCLC of adenocarcinoma histology.
He said that savolitinib appears to be similar in performance to two other TKIs for NSCLC with MET exon-14 skipping mutations that are currently on the market in the United States, Europe, and Japan: capmatinib (Tabrecta) and tepotinib (Tepmetko).
“Globally, all the results show a numerically better performance when we use a selective TKI in first-line treatment over the second-line treatment, in particular for overall response rate,” he said.
Dr. Passaro noted that savolitinib differs from the other two MET TKIs in that PFS with savolitinib is similar for treatment-naive and previously treated patients.
He added, however, that “today it’s very difficult” to determine which is the “perfect” agent for a specific disease presentation, particularly since MET exon 14 skipping mutations can also be found in patients with squamous cell carcinomas and those with a history of smoking.
To get a better sense of which drug to use in a specific situation, it would be helpful to analyze trial results in the context of tumor histology, smoking history, programmed death protein 1-ligand 1 status, and co-mutations, he said.
The study was sponsored by Hutchmed. Dr. Zhang reported having no conflicts of interest. Dr. Passaro reported a consulting, advisory, or speakers bureau role for multiple companies, not including Hutchmed.
Savolitinib, a selective oral tyrosine kinase inhibitor, showed good activity against locally advanced or metastatic non–small cell lung cancer (NSCLC) bearing MET exon 14 mutations as both first-line therapy for treatment-naive patients and in second-line of therapy for previously treated patients
“The phase 3b study results further confirm savolitinib as a valuable targeted therapy option for naive and previously-treated non–small cell lung cancer with MET 14 exon mutations,” Yongchang Zhang, MD, said while presenting the final results of the trial at the European Lung Cancer Congress 2024.
For 87 previously untreated patients the objective response rate (ORR) as assessed by independent review, the primary endpoint, was 62.1%. For 79 patients receiving savolitinib in the second line, the ORR was 39.2%, reported Dr. Zhang, MD, of the Hunan Cancer Hospital in Changsha, China.
Preliminary results of this trial were reported at the World Conference on Lung Cancer in 2023.
Selective Inhibitor
Savolitinib (AZD6094, also called volitinib) is reported to be a highly selective oral inhibitor of the MET receptor tyrosine kinase (TKI). It is approved in China for the treatment of patients with NSCLC harboring MET exon 14 mutations that has progressed on prior systemic therapy, or patients who are unable to tolerate platinum-based chemotherapy.
In the phase 3b study, patients with MET ex14-positive tumors who were negative for EGFR, ALK or ROS1 alterations and were naive to a MET inhibitor were enrolled. Those who weighed 50 kg or greater received 600 mg savolitinib orally once daily for each 21-day cycle, while patients who weighed less than 50 kg received a 400-mg daily dose. Therapy continued until disease progression, death, or unacceptable toxicity.
Tumors were evaluated by investigators every 6 weeks for the first year, than every 12 weeks thereafter.
As noted before, ORR by independent review was 62.1% for treatment-naive patients and 39.2% for previously treated patients. The respective ORRs by investigator assessment were 59.8% and 43%. All responses in each arm were partial responses.
Median progression-free survival (PFS) after a median follow-up of 18 months for treatment-naive patients and 11 months for treatment-experienced patients was 13.7 months and 11 months, respectively.
Overall survival after a median follow-up of 20.8 months for treatment-naive patients and 12.5 months for previously treated patients was not reached in treatment-naive patients and not mature in treatment-experienced patients.
Grade 3 or greater treatment-emergent adverse events occurred in 74.1% of patients, including 3 events (1.8%) leading to death. Dose modifications were required for 74.7% of patients.
Grade 3 or greater adverse events included peripheral edema, liver enzyme elevations, abnormal liver function, decreased platelet and white blood cell counts, and vomiting.
Which TKI is Best?
Invited discussant Antonio Passaro, MD, PhD, from the European Institute of Oncology in Milan, noted that eligibility for treatment with savolitinib or other MET exon 14-targeting TKIs is limited to about 3% of patients with NSCLC of adenocarcinoma histology.
He said that savolitinib appears to be similar in performance to two other TKIs for NSCLC with MET exon-14 skipping mutations that are currently on the market in the United States, Europe, and Japan: capmatinib (Tabrecta) and tepotinib (Tepmetko).
“Globally, all the results show a numerically better performance when we use a selective TKI in first-line treatment over the second-line treatment, in particular for overall response rate,” he said.
Dr. Passaro noted that savolitinib differs from the other two MET TKIs in that PFS with savolitinib is similar for treatment-naive and previously treated patients.
He added, however, that “today it’s very difficult” to determine which is the “perfect” agent for a specific disease presentation, particularly since MET exon 14 skipping mutations can also be found in patients with squamous cell carcinomas and those with a history of smoking.
To get a better sense of which drug to use in a specific situation, it would be helpful to analyze trial results in the context of tumor histology, smoking history, programmed death protein 1-ligand 1 status, and co-mutations, he said.
The study was sponsored by Hutchmed. Dr. Zhang reported having no conflicts of interest. Dr. Passaro reported a consulting, advisory, or speakers bureau role for multiple companies, not including Hutchmed.
FROM ELCC 2024
Few Childhood Cancer Survivors Get Recommended Screenings
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Subcutaneous Immunotherapy Promises Better Life For Cancer Patients
The possibility is being driven by the development of subcutaneous formulations of commonly used immune checkpoint inhibitors for non–small cell lung cancer (NSCLC) and other indications, including pembrolizumab, nivolumab, durvalumab, atezolizumab, and amivantamab.
Instead of waiting anywhere from 30 minutes to several hours for infusions into their veins, patients would spend just a few minutes being injected under the loose skin of their abdomens or thighs. Clinicians would save time and money, and patients would leave the clinic much sooner than normal. The ease of subcutaneous injections also opens up an opportunity for home treatment, a potential boon for people who don’t want to spend their remaining time on hospital visits.
“In the future, I hope we can deliver these medicines at home,” said Hazel O’Sullivan, MBBCh, a medical lung cancer oncologist at Cork University, Ireland, who explained the issues during a session at the 2024 European Lung Cancer Congress.
She was the discussant on two studies at the meeting that highlighted the latest developments in the field, the IMscin002 study of subcutaneous atezolizumab and the PALOMA study of subcutaneous amivantamab, both mostly in NSCLC patients.
Subcutaneous atezolizumab was approved recently in Europe after its maker, Genentech/Roche, made a convincing case that its pharmacokinetics, efficacy, and safety are comparable to the intravenous (IV) version. The U.S. Food and Drug Administration is considering approval; Genentech/Roche anticipates a decision in 2024.
IMscin002 randomized 179 stage 2-4 NSCLC patients evenly to IV or subcutaneous atezolizumab for the first three cycles, then switched them for three more cycles.
Participants were then asked what version they preferred and what they wanted to continue with.
Seventy-one percent said they liked the subcutaneous version better and 80% opted to continue with it. Their main reasons were because they spent less time in the clinic and it was more comfortable.
When asked about the potential for home administration, presenter Federico Cappuzzo, MD, PhD, a medical lung cancer oncologist in Rome, said that it could be “an important option in the future,” particularly in isolated areas far away from hospitals.
The authors of new research are currently evaluating whether home administration is possible. Nurses are administering atezolizumab to patients in their homes with telemedicine monitoring.
The other subcutaneous study presented at the meeting, the PALOMA trial with amivantamab, had only 19 subjects. Administration took no more than 10 minutes, versus potentially hours, especially for the first dose. Subcutaneous amivantamab was given once a month, versus every 2 weeks for the IV formulation, during the maintenance phase of treatment.
The take-home from PALOMA is that the risk of infusion reactions is lower with subcutaneous administration (16% versus 67%) but the risk of mostly mild skin rashes is higher (79% versus 36%).
Investigation is ongoing to confirm safety, pharmacokinetic, and efficacy equivalence with the IV formulation, including in combination with other medications.
When asked about home administration of amivantamab, PALOMA lead investigator Natasha Leighl, MD, a lung, and breast cancer medical oncologist at the University of Toronto, stated that patients probably need to be watched in the clinic for the first 4 months.
The atezolizumab study was funded by maker Genentech/Roche. The amivantamab study was funded by its maker, Janssen. The amivantamab investigator, Dr. Leighl, reported grants, honoraria, and travel payments from Janssen. Dr. Cappuzzo, the investigator on the atezolizumab study, reported speaker and adviser payments from Genentech/Roche. The discussant, Dr. O’Sullivan, wasn’t involved with either company but reported payments from Amgen and AstraZeneca and travel costs covered by Takeda.
The possibility is being driven by the development of subcutaneous formulations of commonly used immune checkpoint inhibitors for non–small cell lung cancer (NSCLC) and other indications, including pembrolizumab, nivolumab, durvalumab, atezolizumab, and amivantamab.
Instead of waiting anywhere from 30 minutes to several hours for infusions into their veins, patients would spend just a few minutes being injected under the loose skin of their abdomens or thighs. Clinicians would save time and money, and patients would leave the clinic much sooner than normal. The ease of subcutaneous injections also opens up an opportunity for home treatment, a potential boon for people who don’t want to spend their remaining time on hospital visits.
“In the future, I hope we can deliver these medicines at home,” said Hazel O’Sullivan, MBBCh, a medical lung cancer oncologist at Cork University, Ireland, who explained the issues during a session at the 2024 European Lung Cancer Congress.
She was the discussant on two studies at the meeting that highlighted the latest developments in the field, the IMscin002 study of subcutaneous atezolizumab and the PALOMA study of subcutaneous amivantamab, both mostly in NSCLC patients.
Subcutaneous atezolizumab was approved recently in Europe after its maker, Genentech/Roche, made a convincing case that its pharmacokinetics, efficacy, and safety are comparable to the intravenous (IV) version. The U.S. Food and Drug Administration is considering approval; Genentech/Roche anticipates a decision in 2024.
IMscin002 randomized 179 stage 2-4 NSCLC patients evenly to IV or subcutaneous atezolizumab for the first three cycles, then switched them for three more cycles.
Participants were then asked what version they preferred and what they wanted to continue with.
Seventy-one percent said they liked the subcutaneous version better and 80% opted to continue with it. Their main reasons were because they spent less time in the clinic and it was more comfortable.
When asked about the potential for home administration, presenter Federico Cappuzzo, MD, PhD, a medical lung cancer oncologist in Rome, said that it could be “an important option in the future,” particularly in isolated areas far away from hospitals.
The authors of new research are currently evaluating whether home administration is possible. Nurses are administering atezolizumab to patients in their homes with telemedicine monitoring.
The other subcutaneous study presented at the meeting, the PALOMA trial with amivantamab, had only 19 subjects. Administration took no more than 10 minutes, versus potentially hours, especially for the first dose. Subcutaneous amivantamab was given once a month, versus every 2 weeks for the IV formulation, during the maintenance phase of treatment.
The take-home from PALOMA is that the risk of infusion reactions is lower with subcutaneous administration (16% versus 67%) but the risk of mostly mild skin rashes is higher (79% versus 36%).
Investigation is ongoing to confirm safety, pharmacokinetic, and efficacy equivalence with the IV formulation, including in combination with other medications.
When asked about home administration of amivantamab, PALOMA lead investigator Natasha Leighl, MD, a lung, and breast cancer medical oncologist at the University of Toronto, stated that patients probably need to be watched in the clinic for the first 4 months.
The atezolizumab study was funded by maker Genentech/Roche. The amivantamab study was funded by its maker, Janssen. The amivantamab investigator, Dr. Leighl, reported grants, honoraria, and travel payments from Janssen. Dr. Cappuzzo, the investigator on the atezolizumab study, reported speaker and adviser payments from Genentech/Roche. The discussant, Dr. O’Sullivan, wasn’t involved with either company but reported payments from Amgen and AstraZeneca and travel costs covered by Takeda.
The possibility is being driven by the development of subcutaneous formulations of commonly used immune checkpoint inhibitors for non–small cell lung cancer (NSCLC) and other indications, including pembrolizumab, nivolumab, durvalumab, atezolizumab, and amivantamab.
Instead of waiting anywhere from 30 minutes to several hours for infusions into their veins, patients would spend just a few minutes being injected under the loose skin of their abdomens or thighs. Clinicians would save time and money, and patients would leave the clinic much sooner than normal. The ease of subcutaneous injections also opens up an opportunity for home treatment, a potential boon for people who don’t want to spend their remaining time on hospital visits.
“In the future, I hope we can deliver these medicines at home,” said Hazel O’Sullivan, MBBCh, a medical lung cancer oncologist at Cork University, Ireland, who explained the issues during a session at the 2024 European Lung Cancer Congress.
She was the discussant on two studies at the meeting that highlighted the latest developments in the field, the IMscin002 study of subcutaneous atezolizumab and the PALOMA study of subcutaneous amivantamab, both mostly in NSCLC patients.
Subcutaneous atezolizumab was approved recently in Europe after its maker, Genentech/Roche, made a convincing case that its pharmacokinetics, efficacy, and safety are comparable to the intravenous (IV) version. The U.S. Food and Drug Administration is considering approval; Genentech/Roche anticipates a decision in 2024.
IMscin002 randomized 179 stage 2-4 NSCLC patients evenly to IV or subcutaneous atezolizumab for the first three cycles, then switched them for three more cycles.
Participants were then asked what version they preferred and what they wanted to continue with.
Seventy-one percent said they liked the subcutaneous version better and 80% opted to continue with it. Their main reasons were because they spent less time in the clinic and it was more comfortable.
When asked about the potential for home administration, presenter Federico Cappuzzo, MD, PhD, a medical lung cancer oncologist in Rome, said that it could be “an important option in the future,” particularly in isolated areas far away from hospitals.
The authors of new research are currently evaluating whether home administration is possible. Nurses are administering atezolizumab to patients in their homes with telemedicine monitoring.
The other subcutaneous study presented at the meeting, the PALOMA trial with amivantamab, had only 19 subjects. Administration took no more than 10 minutes, versus potentially hours, especially for the first dose. Subcutaneous amivantamab was given once a month, versus every 2 weeks for the IV formulation, during the maintenance phase of treatment.
The take-home from PALOMA is that the risk of infusion reactions is lower with subcutaneous administration (16% versus 67%) but the risk of mostly mild skin rashes is higher (79% versus 36%).
Investigation is ongoing to confirm safety, pharmacokinetic, and efficacy equivalence with the IV formulation, including in combination with other medications.
When asked about home administration of amivantamab, PALOMA lead investigator Natasha Leighl, MD, a lung, and breast cancer medical oncologist at the University of Toronto, stated that patients probably need to be watched in the clinic for the first 4 months.
The atezolizumab study was funded by maker Genentech/Roche. The amivantamab study was funded by its maker, Janssen. The amivantamab investigator, Dr. Leighl, reported grants, honoraria, and travel payments from Janssen. Dr. Cappuzzo, the investigator on the atezolizumab study, reported speaker and adviser payments from Genentech/Roche. The discussant, Dr. O’Sullivan, wasn’t involved with either company but reported payments from Amgen and AstraZeneca and travel costs covered by Takeda.
FROM ELCC 2024
Lung Cancer Screening Unveils Hidden Health Risks
The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.
In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.
With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.
Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.
The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.
Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.
The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.
It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.
At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.
To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.
Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.
Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.
The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.
The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.
The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.
4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.
The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.
In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.
With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.
Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.
The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.
Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.
The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.
It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.
At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.
To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.
Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.
Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.
The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.
The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.
The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.
4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.
The reason is because the low-dose CT scans used for screening cover the lower neck down to the upper abdomen, revealing far more anatomy than simply the lungs.
In fact, lung cancer screening can provide information on three of the top 10 causes of death worldwide: ischemic heart disease, chronic obstructive pulmonary disease, and, of course, lung cancer.
With lung cancer screening, “we are basically targeting many birds with one low-dose stone,” explained Jelena Spasic MD, PhD, at the European Lung Cancer Congress (ELCC) 2024.
Dr. Spasic, a medical oncologist at the Institute for Oncology and Radiology of Serbia in Belgrade, was the discussant on a study that gave an indication on just how useful screening can be for other diseases.
The study, dubbed 4-IN-THE-LUNG-RUN trial (4ITLR), is an ongoing prospective trial in six European countries that is using lung cancer screening scans to also look for coronary artery calcifications, a marker of atherosclerosis.
Usually, coronary calcifications are considered incidental findings on lung cancer screenings and reported to subjects’ physicians for heart disease risk assessment.
The difference in 4ITLR is that investigators are actively looking for the lesions and quantifying the extent of calcifications.
It’s made possible by the artificial intelligence-based software being used to read the scans. In addition to generating reports on lung nodules, it also automatically calculates an Agatston score, a quantification of the degree of coronary artery calcification for each subject.
At the meeting, which was organized by the European Society for Clinical Oncology, 4ITLR investigator Daiwei Han, MD, PhD, a research associate at the Institute for Diagnostic Accuracy in Groningen, the Netherlands, reported outcomes in the first 2487 of the 24,000 planned subjects.
To be eligible for screening, participants had to be 60-79 years old and either current smokers, past smokers who had quit within 10 years, or people with a 35 or more pack-year history. The median age in the study was 68.1 years.
Overall, 53% of subjects had Agatston scores of 100 or more, indicating the need for treatment to prevent active coronary artery disease, Dr. Han said.
Fifteen percent were at high risk for heart disease with scores of 400-999, indicating extensive coronary artery calcification, and 16.2% were at very high risk, with scores of 1000 or higher. The information is being shared with participants’ physicians.
The risk of heart disease was far higher in men, who made up 56% of the study population. While women had a median Agatston score of 61, the median score for men was 211.1.
The findings illustrate the potential of dedicated cardiovascular screening within lung cancer screening programs, Dr. Han said, noting that 4ITLR will also incorporate COPD risk assessment.
The study also shows the increased impact lung cancer screening programs could have if greater use were made of the CT images to look for other diseases, Dr. Spasic said.
4ITLR is funded by the European Union’s Horizon 2020 Program. Dr. Spasic and Dr. Han didn’t have any relevant disclosures.
FROM ELCC 2024
VA to Expand Cancer Prevention Services
The US Department of Veterans Affairs (VA) announced plans to expand preventive services, health care, and benefits for veterans with cancer.
Urethral cancers are set to be added to the list of > 300 conditions considered presumptive under the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act of 2022. Veterans deployed to Iraq, Afghanistan, Somalia, Djibouti, Egypt, Jordan, Lebanon, Syria, Yemen, Uzbekistan, and the entire Southwest Asia theater will not need to prove their service caused their urethral cancer in order to receive treatment for it. Additionally, the VA plans to evaluate whether there is a relationship between urinary bladder and ureteral cancers and toxic exposures for these veterans, and determine whether these conditions are presumptive. The VA has already screened > 5 million veterans for toxic exposures under the PACT Act, as part of an ongoing mission to expand cancer care services.
The VA is also set to expand access to screening programs in 2024 by providing:
- genetic testing to every veteran who may need it;
- lung cancer screening programs to every VA medical center; and
- home tests for colorectal cancer to > 1 million veterans nationwide.
The VA continues to expand the reach of smoking cessation services, with ≥ 6 additional sites added to the Quit VET eReferral program by the end of 2024, and a new pilot program to integrate smoking cessation services into lung cancer screening.
The VA has already taken steps to build on the Biden-Harris Administration Cancer Moonshot program, which has the goals of preventing ≥ 4 million cancer deaths by 2047 and to improve the experience of individuals with cancer. For instance, it has prioritized claims processing for veterans with cancer and expanded cancer risk assessments and mammograms to veterans aged < 40 years, regardless of age, symptoms, family history, or whether they are enrolled in VA health care. In September, the VA and the National Cancer Institute announced a data-sharing collaboration to better understand and treat cancer among veterans.
“VA is planting the seeds for the future of cancer care,” said VHA Under Secretary for Health Shereef Elnahal, MD. “By investing in screenings, expanding access, and embracing cutting-edge technologies, VA is revolutionizing cancer care delivery, providing the best care possible to our nation’s heroes.”
The US Department of Veterans Affairs (VA) announced plans to expand preventive services, health care, and benefits for veterans with cancer.
Urethral cancers are set to be added to the list of > 300 conditions considered presumptive under the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act of 2022. Veterans deployed to Iraq, Afghanistan, Somalia, Djibouti, Egypt, Jordan, Lebanon, Syria, Yemen, Uzbekistan, and the entire Southwest Asia theater will not need to prove their service caused their urethral cancer in order to receive treatment for it. Additionally, the VA plans to evaluate whether there is a relationship between urinary bladder and ureteral cancers and toxic exposures for these veterans, and determine whether these conditions are presumptive. The VA has already screened > 5 million veterans for toxic exposures under the PACT Act, as part of an ongoing mission to expand cancer care services.
The VA is also set to expand access to screening programs in 2024 by providing:
- genetic testing to every veteran who may need it;
- lung cancer screening programs to every VA medical center; and
- home tests for colorectal cancer to > 1 million veterans nationwide.
The VA continues to expand the reach of smoking cessation services, with ≥ 6 additional sites added to the Quit VET eReferral program by the end of 2024, and a new pilot program to integrate smoking cessation services into lung cancer screening.
The VA has already taken steps to build on the Biden-Harris Administration Cancer Moonshot program, which has the goals of preventing ≥ 4 million cancer deaths by 2047 and to improve the experience of individuals with cancer. For instance, it has prioritized claims processing for veterans with cancer and expanded cancer risk assessments and mammograms to veterans aged < 40 years, regardless of age, symptoms, family history, or whether they are enrolled in VA health care. In September, the VA and the National Cancer Institute announced a data-sharing collaboration to better understand and treat cancer among veterans.
“VA is planting the seeds for the future of cancer care,” said VHA Under Secretary for Health Shereef Elnahal, MD. “By investing in screenings, expanding access, and embracing cutting-edge technologies, VA is revolutionizing cancer care delivery, providing the best care possible to our nation’s heroes.”
The US Department of Veterans Affairs (VA) announced plans to expand preventive services, health care, and benefits for veterans with cancer.
Urethral cancers are set to be added to the list of > 300 conditions considered presumptive under the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act of 2022. Veterans deployed to Iraq, Afghanistan, Somalia, Djibouti, Egypt, Jordan, Lebanon, Syria, Yemen, Uzbekistan, and the entire Southwest Asia theater will not need to prove their service caused their urethral cancer in order to receive treatment for it. Additionally, the VA plans to evaluate whether there is a relationship between urinary bladder and ureteral cancers and toxic exposures for these veterans, and determine whether these conditions are presumptive. The VA has already screened > 5 million veterans for toxic exposures under the PACT Act, as part of an ongoing mission to expand cancer care services.
The VA is also set to expand access to screening programs in 2024 by providing:
- genetic testing to every veteran who may need it;
- lung cancer screening programs to every VA medical center; and
- home tests for colorectal cancer to > 1 million veterans nationwide.
The VA continues to expand the reach of smoking cessation services, with ≥ 6 additional sites added to the Quit VET eReferral program by the end of 2024, and a new pilot program to integrate smoking cessation services into lung cancer screening.
The VA has already taken steps to build on the Biden-Harris Administration Cancer Moonshot program, which has the goals of preventing ≥ 4 million cancer deaths by 2047 and to improve the experience of individuals with cancer. For instance, it has prioritized claims processing for veterans with cancer and expanded cancer risk assessments and mammograms to veterans aged < 40 years, regardless of age, symptoms, family history, or whether they are enrolled in VA health care. In September, the VA and the National Cancer Institute announced a data-sharing collaboration to better understand and treat cancer among veterans.
“VA is planting the seeds for the future of cancer care,” said VHA Under Secretary for Health Shereef Elnahal, MD. “By investing in screenings, expanding access, and embracing cutting-edge technologies, VA is revolutionizing cancer care delivery, providing the best care possible to our nation’s heroes.”
Upfront Low-Dose Radiation Improves Advanced SCLC Outcomes
The analysis, presented at the 2024 European Lung Cancer Congress, revealed that low-dose radiation improved patients’ median progression-free and overall survival compared with standard first-line treatment, reported in a 2019 trial, lead author Yan Zhang, MD, reported.
The standard first-line treatment results came from the 2019 CASPIAN trial, which found that patients receiving the first-line regimen had a median progression-free survival of 5 months and a median overall survival of 13 months, with 54% of patient alive at 1 year.
The latest data, which included a small cohort of 30 patients, revealed that adding low-dose radiation to the standard first-line therapy led to a higher median progression-free survival of 8.3 months and extended median overall survival beyond the study follow-up period of 17.3 months. Overall, 66% of patients were alive at 1 year.
These are “promising” improvements over CASPIAN, Dr. Zhang, a lung cancer medical oncologist at Sichuan University, Chengdu, China, said at the Congress, which was organized by the European Society for Medical Oncology.
Study discussant Gerry Hanna, PhD, MBBS, a radiation oncologist at Belfast City Hospital, Belfast, Northern Ireland, agreed. Although there were just 30 patients, “you cannot deny these are [strong] results in terms of extensive-stage small cell cancer,” Dr. Hanna said.
Although standard first-line treatment of extensive-stage SCLC is durvalumab plus etoposide-platinum chemotherapy, the benefits aren’t durable for many patients.
This problem led Dr. Zhang and his colleagues to look for ways to improve outcomes. Because the CASPIAN trial did not include radiation to the primary tumor, it seemed a logical strategy to explore.
In the current single-arm study, Dr. Zhang and his team added 15 Gy radiation in five fractions to the primary lung tumors of 30 patients during the first cycle of durvalumab plus etoposide-platinum.
Subjects received 1500 mg of durvalumab plus etoposide-platinum every 3 weeks for four cycles. Low-dose radiation to the primary tumor was delivered over 5 days at the start of treatment. Patients then continued with durvalumab maintenance every 4 weeks until progression or intolerable toxicity.
Six patients (20%) had liver metastases at the baseline, and three (10%) had brain metastases. Over half had prophylactic cranial radiation. Performance scores were 0-1, and all but one of the participants were men.
Six- and 12-month progression-free survival rates were 57% and 40%, respectively. Overall survival was 90% at 6 months and 66% at 12 months. Median overall survival was 13 months in the CASPIAN trial but not reached in Dr. Zhang’s trial after a median follow-up of 17.3 months, with the earliest deaths occurring at 10.8 months.
Grade 3 treatment-related adverse events occurred in 80% of patients, most frequently hematologic toxicities. Five patients (16.7%) had severe adverse reactions to radiation. Although the overall dose of radiation was low, at 3 Gy each, the fractions were on the large side.
Hanna wanted more information on the radiotoxicity issue, but even so, he said that adding low-dose radiation to our durvalumab-chemotherapy doublet warrants further investigation.
Both Dr. Hanna and Dr. Zhang thought that instead of killing cancer cells directly, the greatest benefit of upfront radiation, and the peritumoral inflammation it causes, is to augment durvalumab’s effect.
Overall, Dr. Hanna stressed that we haven’t had results like these before in a SCLC study, particularly for novel agents, let alone radiation.
The study was funded by AstraZeneca, maker of durvalumab. Dr. Zhang and Dr. Hanna didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
The analysis, presented at the 2024 European Lung Cancer Congress, revealed that low-dose radiation improved patients’ median progression-free and overall survival compared with standard first-line treatment, reported in a 2019 trial, lead author Yan Zhang, MD, reported.
The standard first-line treatment results came from the 2019 CASPIAN trial, which found that patients receiving the first-line regimen had a median progression-free survival of 5 months and a median overall survival of 13 months, with 54% of patient alive at 1 year.
The latest data, which included a small cohort of 30 patients, revealed that adding low-dose radiation to the standard first-line therapy led to a higher median progression-free survival of 8.3 months and extended median overall survival beyond the study follow-up period of 17.3 months. Overall, 66% of patients were alive at 1 year.
These are “promising” improvements over CASPIAN, Dr. Zhang, a lung cancer medical oncologist at Sichuan University, Chengdu, China, said at the Congress, which was organized by the European Society for Medical Oncology.
Study discussant Gerry Hanna, PhD, MBBS, a radiation oncologist at Belfast City Hospital, Belfast, Northern Ireland, agreed. Although there were just 30 patients, “you cannot deny these are [strong] results in terms of extensive-stage small cell cancer,” Dr. Hanna said.
Although standard first-line treatment of extensive-stage SCLC is durvalumab plus etoposide-platinum chemotherapy, the benefits aren’t durable for many patients.
This problem led Dr. Zhang and his colleagues to look for ways to improve outcomes. Because the CASPIAN trial did not include radiation to the primary tumor, it seemed a logical strategy to explore.
In the current single-arm study, Dr. Zhang and his team added 15 Gy radiation in five fractions to the primary lung tumors of 30 patients during the first cycle of durvalumab plus etoposide-platinum.
Subjects received 1500 mg of durvalumab plus etoposide-platinum every 3 weeks for four cycles. Low-dose radiation to the primary tumor was delivered over 5 days at the start of treatment. Patients then continued with durvalumab maintenance every 4 weeks until progression or intolerable toxicity.
Six patients (20%) had liver metastases at the baseline, and three (10%) had brain metastases. Over half had prophylactic cranial radiation. Performance scores were 0-1, and all but one of the participants were men.
Six- and 12-month progression-free survival rates were 57% and 40%, respectively. Overall survival was 90% at 6 months and 66% at 12 months. Median overall survival was 13 months in the CASPIAN trial but not reached in Dr. Zhang’s trial after a median follow-up of 17.3 months, with the earliest deaths occurring at 10.8 months.
Grade 3 treatment-related adverse events occurred in 80% of patients, most frequently hematologic toxicities. Five patients (16.7%) had severe adverse reactions to radiation. Although the overall dose of radiation was low, at 3 Gy each, the fractions were on the large side.
Hanna wanted more information on the radiotoxicity issue, but even so, he said that adding low-dose radiation to our durvalumab-chemotherapy doublet warrants further investigation.
Both Dr. Hanna and Dr. Zhang thought that instead of killing cancer cells directly, the greatest benefit of upfront radiation, and the peritumoral inflammation it causes, is to augment durvalumab’s effect.
Overall, Dr. Hanna stressed that we haven’t had results like these before in a SCLC study, particularly for novel agents, let alone radiation.
The study was funded by AstraZeneca, maker of durvalumab. Dr. Zhang and Dr. Hanna didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
The analysis, presented at the 2024 European Lung Cancer Congress, revealed that low-dose radiation improved patients’ median progression-free and overall survival compared with standard first-line treatment, reported in a 2019 trial, lead author Yan Zhang, MD, reported.
The standard first-line treatment results came from the 2019 CASPIAN trial, which found that patients receiving the first-line regimen had a median progression-free survival of 5 months and a median overall survival of 13 months, with 54% of patient alive at 1 year.
The latest data, which included a small cohort of 30 patients, revealed that adding low-dose radiation to the standard first-line therapy led to a higher median progression-free survival of 8.3 months and extended median overall survival beyond the study follow-up period of 17.3 months. Overall, 66% of patients were alive at 1 year.
These are “promising” improvements over CASPIAN, Dr. Zhang, a lung cancer medical oncologist at Sichuan University, Chengdu, China, said at the Congress, which was organized by the European Society for Medical Oncology.
Study discussant Gerry Hanna, PhD, MBBS, a radiation oncologist at Belfast City Hospital, Belfast, Northern Ireland, agreed. Although there were just 30 patients, “you cannot deny these are [strong] results in terms of extensive-stage small cell cancer,” Dr. Hanna said.
Although standard first-line treatment of extensive-stage SCLC is durvalumab plus etoposide-platinum chemotherapy, the benefits aren’t durable for many patients.
This problem led Dr. Zhang and his colleagues to look for ways to improve outcomes. Because the CASPIAN trial did not include radiation to the primary tumor, it seemed a logical strategy to explore.
In the current single-arm study, Dr. Zhang and his team added 15 Gy radiation in five fractions to the primary lung tumors of 30 patients during the first cycle of durvalumab plus etoposide-platinum.
Subjects received 1500 mg of durvalumab plus etoposide-platinum every 3 weeks for four cycles. Low-dose radiation to the primary tumor was delivered over 5 days at the start of treatment. Patients then continued with durvalumab maintenance every 4 weeks until progression or intolerable toxicity.
Six patients (20%) had liver metastases at the baseline, and three (10%) had brain metastases. Over half had prophylactic cranial radiation. Performance scores were 0-1, and all but one of the participants were men.
Six- and 12-month progression-free survival rates were 57% and 40%, respectively. Overall survival was 90% at 6 months and 66% at 12 months. Median overall survival was 13 months in the CASPIAN trial but not reached in Dr. Zhang’s trial after a median follow-up of 17.3 months, with the earliest deaths occurring at 10.8 months.
Grade 3 treatment-related adverse events occurred in 80% of patients, most frequently hematologic toxicities. Five patients (16.7%) had severe adverse reactions to radiation. Although the overall dose of radiation was low, at 3 Gy each, the fractions were on the large side.
Hanna wanted more information on the radiotoxicity issue, but even so, he said that adding low-dose radiation to our durvalumab-chemotherapy doublet warrants further investigation.
Both Dr. Hanna and Dr. Zhang thought that instead of killing cancer cells directly, the greatest benefit of upfront radiation, and the peritumoral inflammation it causes, is to augment durvalumab’s effect.
Overall, Dr. Hanna stressed that we haven’t had results like these before in a SCLC study, particularly for novel agents, let alone radiation.
The study was funded by AstraZeneca, maker of durvalumab. Dr. Zhang and Dr. Hanna didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ELCC 2024
Most Cancer Trial Centers Located Closer to White, Affluent Populations
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
FROM JAMA ONCOLOGY
New Drug Approvals Are the Wrong Metric for Cancer Policy
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.