Meeting NewsPerspective

Broader inclusion criteria could double the number of patients with lung cancer eligible for clinical trials

Harvey_Donald_80x106
R. Donald Harvey

CHICAGO — The use of expanded eligibility criteria would allow nearly twice as many people with non-small cell lung cancer to participate in clinical trials, according to data presented at ASCO Annual Meeting.

The study is the result of a joint project between ASCO and the nonprofit advocacy group Friends of Cancer Research, which issued recommendations for expanding clinical trial access.

“Opening up clinical trial eligibility would allow more patients to participate in clinical trial research, and the data generated will be more generalizable to the population of individuals that we see in the clinic,” R. Donald Harvey, PharmD, BCOP, FCCP, FHOPA, director of the Winship Cancer Institute's phase 1 clinical trials section and associate professor at Emory University School of Medicine, said during a press conference. “It will accelerate accrual to these clinical trials and will bring new therapies to these patients more quickly.”.

Harvey said that several groups are implementing the expanded criteria recommended by ASCO, including the FDA, NCI and National Clinical Trials Network.

The researchers conducted a retrospective study of 10,500 patients who received treatment after a diagnosis of advanced NSCLC from January 2011 to December 2018.

The purpose of the study was to determine the number of patients who would be excluded from a trial when comparing traditional study criteria with expanded criteria recommended by ASCO and Friends of Cancer Research.

The traditional clinical trial exclusion criteria used in this analysis were:

patients with another primary cancer within 2 years of trial enrollment;

patients with brain metastases; and

patients with creatinine clearance less than 60 mL/min.

The broadened eligibility criteria recommended by ASCO would allow enrollment of patients with another primary cancer if participation in the trial would not interfere with the patient’s safety or the efficacy of the therapy being tested. It would also allow patients with treated and/or stable brain metastases and patients with a creatinine clearance of 30 mL/min or greater if they would not experience kidney toxicity.

The study used anonymized electronic health records from the ASCO CancerLinQ Discovery database. NSCLC was chosen because of the availability of many scientific trials for the disease state and because patients with NSCLC often have more advanced stages of the disease and comorbidities.

The study group’s median age was 67.6 years (interquartile range, 60.3-74.4 years); most participants were men (56%), white (60%), former smokers (80%) and had stage IV NSCLC (60%).

The results showed that nearly half (47.7%) of patients in the study would have been prohibited from clinical trial participation using traditional exclusion criteria. Conversely, only 1.5% of the study population would have been excluded using the broadened criteria recommended by ASCO.

The traditional criteria would have excluded 21.2% of patients because of brain metastases, 14.4% because of previous cancer and 21.5% because of inadequate creatinine clearance. Creatinine clearance level was the only criterion resulting in the exclusion of patients in the study group when evaluated against the broadened trial participation requirements.

Patients who were eligible due to the expanded criteria were older (67.5 vs. 66.1 years; P < .001) and more likely to be female (44% vs. 40%), have stage IV disease (60% vs. 55%) and have never smoked (16% vs. 13%).

“Narrower criteria to exclude patients from clinical trials should only be used based on compelling scientific rationale,” Harvey said. “At this point, ASCO and the Friends of Cancer Research urge all clinical trial sponsors to adopt these criteria.” – by Drew Amorosi

References:

Harvey RD, et al. Abstract LBA108. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Kim ES, et al. J Clin Oncol. 2017;doi:10.1200/JCO.2017.73.7916.

Disclosures: Harvey reports consultant/advisory roles with Bristol-Myers Squibb, Genentech, Spectrum Pharmaceuticals and Takeda; and institutional research funding from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boston Biomedical, Calithera Biosciences, Celgene, Corvus Pharmaceuticals, Eli Lilly, Five Prime Therapeutics, Genmab, Halozyme, Incyte, Merck, Nektar, Novartis, Pfizer, Rgenix, Sanofi, Takeda, Tesaro and Xencor. Please see the study for all other authors’ relevant financial disclosures.

Harvey_Donald_80x106
R. Donald Harvey

CHICAGO — The use of expanded eligibility criteria would allow nearly twice as many people with non-small cell lung cancer to participate in clinical trials, according to data presented at ASCO Annual Meeting.

The study is the result of a joint project between ASCO and the nonprofit advocacy group Friends of Cancer Research, which issued recommendations for expanding clinical trial access.

“Opening up clinical trial eligibility would allow more patients to participate in clinical trial research, and the data generated will be more generalizable to the population of individuals that we see in the clinic,” R. Donald Harvey, PharmD, BCOP, FCCP, FHOPA, director of the Winship Cancer Institute's phase 1 clinical trials section and associate professor at Emory University School of Medicine, said during a press conference. “It will accelerate accrual to these clinical trials and will bring new therapies to these patients more quickly.”.

Harvey said that several groups are implementing the expanded criteria recommended by ASCO, including the FDA, NCI and National Clinical Trials Network.

The researchers conducted a retrospective study of 10,500 patients who received treatment after a diagnosis of advanced NSCLC from January 2011 to December 2018.

The purpose of the study was to determine the number of patients who would be excluded from a trial when comparing traditional study criteria with expanded criteria recommended by ASCO and Friends of Cancer Research.

The traditional clinical trial exclusion criteria used in this analysis were:

patients with another primary cancer within 2 years of trial enrollment;

patients with brain metastases; and

patients with creatinine clearance less than 60 mL/min.

The broadened eligibility criteria recommended by ASCO would allow enrollment of patients with another primary cancer if participation in the trial would not interfere with the patient’s safety or the efficacy of the therapy being tested. It would also allow patients with treated and/or stable brain metastases and patients with a creatinine clearance of 30 mL/min or greater if they would not experience kidney toxicity.

The study used anonymized electronic health records from the ASCO CancerLinQ Discovery database. NSCLC was chosen because of the availability of many scientific trials for the disease state and because patients with NSCLC often have more advanced stages of the disease and comorbidities.

The study group’s median age was 67.6 years (interquartile range, 60.3-74.4 years); most participants were men (56%), white (60%), former smokers (80%) and had stage IV NSCLC (60%).

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The results showed that nearly half (47.7%) of patients in the study would have been prohibited from clinical trial participation using traditional exclusion criteria. Conversely, only 1.5% of the study population would have been excluded using the broadened criteria recommended by ASCO.

The traditional criteria would have excluded 21.2% of patients because of brain metastases, 14.4% because of previous cancer and 21.5% because of inadequate creatinine clearance. Creatinine clearance level was the only criterion resulting in the exclusion of patients in the study group when evaluated against the broadened trial participation requirements.

Patients who were eligible due to the expanded criteria were older (67.5 vs. 66.1 years; P < .001) and more likely to be female (44% vs. 40%), have stage IV disease (60% vs. 55%) and have never smoked (16% vs. 13%).

“Narrower criteria to exclude patients from clinical trials should only be used based on compelling scientific rationale,” Harvey said. “At this point, ASCO and the Friends of Cancer Research urge all clinical trial sponsors to adopt these criteria.” – by Drew Amorosi

References:

Harvey RD, et al. Abstract LBA108. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Kim ES, et al. J Clin Oncol. 2017;doi:10.1200/JCO.2017.73.7916.

Disclosures: Harvey reports consultant/advisory roles with Bristol-Myers Squibb, Genentech, Spectrum Pharmaceuticals and Takeda; and institutional research funding from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boston Biomedical, Calithera Biosciences, Celgene, Corvus Pharmaceuticals, Eli Lilly, Five Prime Therapeutics, Genmab, Halozyme, Incyte, Merck, Nektar, Novartis, Pfizer, Rgenix, Sanofi, Takeda, Tesaro and Xencor. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Nathan Pennell

    Nathan Pennell

    Clinical trial participation is not a new controversy, but hopefully the prominence of this study by Harvey and colleagues will emphasize how important this topic is. This is one of the most critically essential messages of the ASCO 2019 Annual Meeting.

    A tiny minority of patients who are eligible for clinical trials end up participating in one, and as a result, not only do patients fail to receive treatments that the trials provide, the trial results end up not representing the patients we would treat in the real world.

    If patients are healthy enough to be in a trial, they should be able to participate in one. If clinical trial sponsors would employ the very common-sense changes suggested by ASCO and the Friends of Cancer Research, almost anyone with cancer would be able to participate in a clinical trial.

    The value to expanding the pool of eligible patients would be that more patients would benefit — we know that patients live longer if they participate in clinical trials. We would be able to accrue to the clinical trials much more quickly so we can answer our questions and get new treatments to patients faster.

    Probably the most important benefit to expanding eligibility is that results would better represent the patients we treat. Drugs are often approved and when they are given to patients who don’t quite fit the criteria of those in the clinical trial, they are a lot more toxic, not as effective and become more difficult to deal with.

    Investigators should start refusing to open trials that don’t liberalize eligibility criteria. There should be less talk about this and more action.

    • Nathan Pennell, MD, PhD
    • Cleveland Clinic Taussig Cancer Center

    Disclosures: Pennell reports consultant roles with Merck, AstraZeneca, Cota, Eli Lilly and Regeneron.

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