Dynamics of eligibility criteria for central nervous system metastases in non-small cell lung cancer randomized clinical trials over time: A systematic review

Although central nervous system (CNS) metastases frequently occur in patients with non-small cell lung cancer (NSCLC), historically these patients have been excluded from clinical trials. However, due to improving NSCLC prognosis, time to develop CNS metastases increases and information on CNS efficacy of systemic treatment is important. We performed a systematic PubMed review (2000-2020) to describe CNS related eligibility and screening criteria over time. Randomized phase III, and for tyrosine kinase inhibitors (TKIs) also randomized phase II trials enrolling advanced/metastatic NSCLC patients were included. 256/1195 trials were included. In 71 %, CNS metastases were eligible, but in only 3% regardless of symptoms/ treatment. Only 37 % required baseline CNS screening (most often TKI and immunotherapy trials), without significant increase over time. A CNS endpoint was pre-specified in 4%. Conclusion: CNS screening and eligibility criteria are heterogenous across trials, and CNS related endpoints are rare. These criteria and endpoints should be improved and harmonized