By Megan Brooks
NEW YORK (Reuters Health) - 5/6/2019
Adopting expanded inclusion criteria for clinical trials would nearly double the percentage of patients with advanced non-small-cell lung cancer (NSCLC) who are eligible to enroll, according to new research.
"Ongoing use of historic, narrow eligibility criteria based on antiquated safety concerns place potentially unnecessary restrictions on trial participants, thus making it increasingly difficult to conduct the clinical trials necessary to demonstrate safety and efficacy of new therapies," Dr. R. Donald Harvey, director of the Winship Cancer Institute of Emory University's Phase I Clinical Trials Section, in Atlanta, said in a statement.
"Changes to eligibility criteria are particularly important as we step further into the era of targeted therapies, including immunotherapies, that have different safety profiles than highly toxic systemic chemotherapies," he added.
The findings were presented June 3 at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
Dr. Harvey and colleagues looked at real-world data from electronic health records in ASCO's CancerLinQ database from 2011 to 2018, focusing on 10,500 adults with advanced NSCLC who had received systemic therapy after diagnosis.
They evaluated the number of patients eligible for clinical trials using traditional criteria and criteria proposed in 2017 by ASCO and Friends of Cancer Research, which allow for brain metastases, previous or current cancer diagnoses, and limited kidney function (creatinine clearance level, or CrCl, as low as 30 mL/min). Traditional criteria do not allow for these conditions and exclude patients with CrCl </= 60 mL/min.
By traditional criteria, 21.2% of patients in the cohort would be excluded due to brain metastases, 14.4% due to prior/concurrent cancers and 21.5% due to CrCL </= 60 mL/min.
"Overall, that excluded just under 48% of all patients in the cohort," Dr. Harvey said during a media briefing.
When broadened criteria were applied, no patients were excluded due to brain metastases or prior/concurrent cancers and patients excluded for CrCl dropped from 21.5% to 1.5%. Overall, this increased the number of patients that would have been eligible to enroll in a clinical trial from 5,495 (52.3%) to 10,346 (98.5%), Dr. Harvey reported.
Patients older than age 75 would benefit the most from broadened criteria, with 16% eligible for clinical trial participation under traditional criteria versus 22% under the broadened criteria, Dr. Harvey noted. Patients in geriatric oncology and older patients in general are "under-represented in trials overall so expanding these three criteria will increase that population by 6%," he said.
"These broadened criteria are likely to result in trial participants that are more reflective of the patients we see in clinics, improving generalizability of the data from these trials. We urge all clinical trial sponsors to adopt these criteria," Dr. Harvey said.
Commenting on this research in a statement, ASCO Expert Dr. David Graham noted that only about 3% of patients with cancer in the United States currently enroll in a clinical trial, "and restrictive eligibility criteria established in an era before advances we have made in supportive care is one reason for this low number."
"This study makes the case for universal adoption of broader clinical trial eligibility criteria," he added, "such as that proposed by ASCO and Friends of Cancer Research, so that more lung cancer patients and others have the opportunity to safely participate in potentially lifesaving research."
"The days of my having to tell my lung cancer patients who also happen to have a clinically insignificant prostate cancer or a breast cancer that is likely cured that they cannot be part of advanced lung cancer care should be eliminated," Dr. Graham commented during the briefing.
Dr. Richard Schilsky, ASCO chief medical officer, who worked on the analysis, said it's important to note he and his colleagues only looked at three exclusion criteria "of what are oftentimes literally dozens of inclusion and exclusion criteria." Therefore, one should not conclude that by rolling back these three criteria, suddenly 98% of lung cancer patients are going to be eligible for clinical trials.
"There are still many other reasons that a patient could be excluded. But that said, the study also illustrates the real value of thinking through very carefully what the inclusion and exclusion criteria are and not having arbitrary exclusion criteria that simply limit a patient's access to a clinical study and not based on any sound scientific or clinical rationale. We are quite pleased to see that our advocacy for these changes is actually very well supported by this analysis," Dr. Schilsky said.
This study received funding from ASCO.