Did Updated FDA Guidance Increase Inclusion of Patients With Brain Metastases in Breast Cancer Trials?

By Kerri Fitzgerald - Last Updated: June 14, 2022

Following updated recommendations from the American Society of Clinical Oncology (ASCO), Friends of Cancer Research (FoCR), and the US Food and Drug Administration (FDA), in which the organizations advised broadening clinical trial eligibility criteria, researchers observed a shift in patterns related to brain metastases exclusion criteria in these trials. The results were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

On October 2, 2017, ASCO, FoCR, and the FDA issued a joint research statement about eligibility criteria for cancer clinical trials. One of the recommendations was to broaden eligibility to include patients with brain metastases. Researchers assessed whether exclusion criteria patterns changed for this patient population following the recommendations.

Researchers used ClinicalTrials.gov to evaluate patterns of trial eligibility criteria in phase 1-3 US-based interventional clinical trials for patients with advanced breast, colorectal, or lung cancers from January 2013 through October 2021. They determined whether patients with brain metastases were not excluded, conditionally excluded (ie, excluded in some circumstances), or wholly excluded. They excluded trials registered between October 2, 2017, and December 31, 2018, to allow 1 year for newly conceived trials to adopt the recommendations, plus 3 months to account for the lag time between loading trial records and trial activation dates.

The final cohort included 1,998 trials, with breast cancer representing 34.3% of trials (n=787). Most trials (56.8%; n=1,133) were phase 2, and about half were industry sponsored (53.7%; n=1,072). A majority (76.2%; n=1,522) were drug intervention trials.

Among the studies assessed, patients with brain metastases were not excluded in 307 trials (15.4%), conditionally excluded in 1,459 trials (74.8%), and wholly excluded in 196 trials (9.8%). Following the new recommendations, there was a 92% increase in the odds of trials with brain metastases not excluded compared with conditionally excluded (odds ratio, 1.92; 95% CI, 1.08-3.45; P=.03).

The estimated proportion of trials in which patients with brain metastases were not excluded increased from 9.2% to 15.6% (P=.04) following the recommendations. Conversely, the proportion of trials in which patients with brain metastases were conditionally excluded (76.9%) was lower than expected (85.3%; P=.02). Researchers found no difference in the proportion of trials in which patients with brain metastases were wholly excluded before and after the recommendations (7.5% vs 5.4%; P=.28).

“To our knowledge, this is the first evidence that cancer clinical trials have become more inclusive of a broader set of patients in response to the ASCO/FoCR/FDA recommendations,” the researchers concluded. “More inclusive eligibility improves trial access and representativeness, increasing trial validity and the pace at which trials enroll.”


Unger JM, Xiao H, Hershman DL, Vaidya R. Impact of broadening trial eligibility criteria on the inclusion of patients with brain metastases in cancer clinical trials. Abstract #1505. Presented at the 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL.

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