Brain metastasis as exclusion criteria in clinical trials involving extensive-stage small cell lung cancer.

Background: The American Society of Clinical Oncology and Friends of Cancer Research submitted recommendations to the FDA to reduce barriers in clinical trial participation. They proposed the removal of several specific exclusion criteria, including brain metastasis. Clinical trials involving small cell lung cancer (SCLC) have varying exclusion criteria regarding brain metastasis.

Methods: We completed an online search of clinicaltrials.gov for the query "SCLC, extensive stage." The trials were classified into a group of strict exclusion, allowed only if treated, allowed without treatment, or undefined. Relationships between status of brain metastasis in exclusion criteria and study characteristics (trial status, trial design, sponsor, location, and treatment groups) were investigated by Chi-squared test. The trends of exclusion status were investigated by a comparison against the variable time.

Results: Of the 204 eligible trials, 32 strictly excluded any form or history of CNS metastases, 129 allowed patients that are undergoing or have undergone CNS-specific therapy, 9 allowed patients without any CNS-specific therapy, and 34 did not mention any criteria involving CNS metastases. Studies conducted outside the United States and with single systemic therapy were associated with strict exclusion of brain metastasis (p = 0.026 and 0.039, respectively). The proportion of clinical trials with strict exclusion has remained around 15% for the past few decades.

Conclusion: Non-US and single systemic therapy studies are more commonly associated with strict exclusion of brain metastasis in ES-SCLC trials. The strict exclusion of brain metastases in clinical trials has remained relatively constant for the past few decades.