Is It Time to Change Clinical Trial Inclusion Criteria in Lung Cancer?

CHICAGO-It may be possible to double the number of patients eligible for clinical trials for advanced non–small-cell lung cancer (NSCLC). A study looking at 10,500 health records of advanced NSCLC patients has found that the use of expanded clinical trial inclusion criteria would nearly double the percentage of patients eligible to enroll in clinical trials, from 52.3% to 98.5%. These results (abstract LBA108) were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago. The expanded clinical trial eligibility criteria would allow advanced NSCLC patients with brain metastases and with limited kidney function to enroll in clinical trials.

Lead study author R. Donald Harvey, PharmD, BCOP, director of the Winship Cancer Institute of Emory University’s Phase I Clinical Trials Section in Atlanta, said that the ongoing use of historic, narrow eligibility criteria based on antiquated safety concerns place potentially unnecessary restrictions on trial participants. He said changes to eligibility criteria are particularly important in the era of targeted therapies, including immunotherapies, which have significantly different safety profiles compared with highly toxic systemic chemotherapies. “Narrower criteria to exclude patients should only be used based on compelling scientific rationale,” said Harvey. “At this point, this group urges all clinical trial sponsors to adopt these criteria.”

Harvey and his colleagues looked at electronic health records from 2011 to 2018 and focused on adults with advanced NSCLC who had two or more oncologist visits and at least one dose of a systemic treatment after diagnosis. The researchers evaluated the number of patients eligible for clinical trials using traditional criteria and using the proposed criteria from ASCO and Friends of Cancer Research. Traditionally, patients have been excluded if they had another primary cancer within 2 years prior to trial enrollment. Under the expanded criteria, patients with another primary cancer that does not interfere with safety or efficacy of the study therapy would be allowed to participate. The expanded criteria would allow for brain metastases (previous or current cancer diagnoses) and creatinine clearance levels as low as 30 mL/min. Traditional criteria do not allow for these conditions and exclude patients with creatinine clearance levels less than 60 mL/min. In November 2018, the National Cancer Institute revised its clinical trial protocol template to broaden eligibility criteria for cancer clinical trials based on the recommendations of ASCO and Friends of Cancer Research.

In this current analysis, 60% of the patients had a stage IV diagnosis, and 80% were former or current smokers. The median age of patients was 67.6 years; 56% were men and 44% were women. When the researchers applied traditional clinical trial enrollment criteria, 5,005 (47.7% of patients) would not meet trial eligibility criteria. However, if the expanded criteria were adopted, then only 154 (1.5% of patients) would not meet eligibility criteria. The researchers concluded that the use of the expanded criteria would allow 4,851 more people to meet eligibility criteria.

Adoption of expanded criteria compared with traditional criteria would also enhance the characteristics of advanced NSCLC patients in clinical trials by expanding the number of older patients, raising the median age from 66.1 to 67.5 years, according to the researchers. It would increase the number of women from 40% to 44% and patients with stage IV diagnoses from 55% to 60%. Broadening trial eligibility would make clinical trial findings in patients with advanced NSCLC “more generalizable to the population of individuals we see in the clinic, and it will accelerate accrual to these trials and optimally bring new therapies to patients more quickly,” said Harvey.

Nicholas Rohs, MD, an assistant professor of medicine, hematology, and medical oncology at the Tisch Cancer Institute at Mount Sinai, New York, told Cancer Network that this is an important study highlighting a reasonable way to improve clinical trial engagement and enrollment, which ultimately leads to better care and outcomes for patients. “I still appreciate the continued importance of clinical trial enrollment criteria to help us ensure the most reliable trial results and, even more importantly, keep our patients safe. However, the improved technology and supportive care options available to medical oncologists today allows us to more closely monitor patient health while on trial, and treat and even prevent complications more effectively than in the past,” he said.

Rohs noted that having broader clinical trial enrollment criteria can significantly help reduce social and economic disparities and allow a better representation of a more “real-world” population in clinical trials. “It also reflects our evolving understanding of clinical trials and the importance of real-life endpoints such as control of CNS disease or tolerability of therapy in patients with impaired renal function. I think this concept is catching on and I hope it continues to grow,” he said.