A retrospective study indicates that relaxing eligibility criteria for clinical trials in metastatic non-small cell lung cancer (NSCLC) could lead to better patient outcomes. The research, presented by investigators at a single academic institution, challenges the stringent inclusion criteria often used in phase 3 trials, particularly for immunotherapy and targeted therapy regimens.
The study, which reviewed data from 170 patients with metastatic NSCLC treated with first-line systemic therapy between 2015 and 2018, assessed whether patients would have been eligible for the clinical trials that led to the approval of their specific treatment regimen. The primary endpoint was the difference in survival time between eligible and ineligible patients.
Impact of Eligibility on Survival
Results showed a statistically significant difference in restricted mean survival time (RMST) between the eligible and ineligible groups among patients who received combined chemotherapy (19.9 months vs. 13.2 months; P = .03). However, no statistically significant differences were observed in the immunotherapy group (22.4 months vs. 12.9 months; P = .06) or the targeted therapy group (57.7 months vs. 39.0 months; P = .14).
"Our data suggest that there is no significant difference in clinical outcomes in terms of survival for individuals with metastatic NSCLC who are eligible to participate in both immunotherapy and targeted-therapy clinical trials compared with those individuals who are ineligible to participate," the authors noted. This suggests that current eligibility criteria for these treatment modalities may be unnecessarily restrictive.
Restrictive Criteria
The study identified several common reasons for ineligibility, including high ECOG performance status and prior malignancy or chemotherapy. Interestingly, 65.5% of ineligible patients failed only one eligibility criterion, suggesting that even minor adjustments to trial design could significantly increase patient participation.
"Even a slight reduction in the number of eligibility criteria could potentially help with study accrual and generalizability," the researchers stated.
Broader Implications
The findings align with ongoing efforts to modernize clinical trial eligibility criteria in oncology. The LUNGevity Foundation, for example, has convened expert working groups to address outdated or unnecessary restrictions in lung cancer trials. Their work focuses on providing scientific justification for reducing criteria that routinely exclude patients, with the goal of standardizing eligibility and simplifying trial populations.
The study's authors acknowledge limitations, including its retrospective, single-institution design and the relatively small number of patients in the immunotherapy and targeted therapy subgroups. They recommend repeat analyses as these treatment regimens become more broadly used.
Despite these limitations, the study provides real-world evidence supporting less restrictive clinical trial eligibility criteria for patients with metastatic NSCLC, particularly in the context of targeted therapy and immunotherapy. Broadening trial inclusion may not only improve accrual but also enhance the generalizability of trial results to a wider patient population.
