Participation of Patients With Gynecologic Cancer in Phase I Clinical Trials: Experience From Two National Cancer Institute–Designated Comprehensive Cancer Centers

Purpose Phase I trials are intended to define the safety of novel therapeutics, yet they offer alternative options long before they are approved. Limited data exist regarding access to and participation in phase I trials among gynecologic oncology patients. The purpose of this study is to assess the efficacy, toxicities, and prognostic factors of phase I trials in advanced gynecologic malignancies. Methods This was a retrospective cohort study of patients with gynecologic malignancies enrolled in phase I clinical trials at two National Cancer Institute–designated Comprehensive Cancer Centers between 2000 and 2022. Demographic, clinical, treatment, and toxicity data were collected via chart review. Overall survival (OS) was estimated using Kaplan-Meier curves. Cox proportional hazards models were used to evaluate prognostic factors, with multiple imputations for missing data. Results Three hundred thirty-five patients were included, with a mean age of 58.8 years (standard deviation, 11.5). Most were heavily pretreated with a median of three prior lines of therapy. The clinical benefit rate among response-evaluable patients was 56.2%, primarily driven by stable disease. The median OS was 1.16 years, with a significant improvement over time, favoring patients enrolled between 2015 and 2022, who had a median OS of 2.17 years ( P < .0001). Non-Hispanic Black patients experienced a higher risk of mortality compared with non-Hispanic White patients. Treatment was generally well tolerated, with only 3.9% experiencing dose-limiting toxicities. Conclusion Phase I clinical trial participation in gynecologic cancers may provide clinically meaningful benefits, favorable toxicity profiles, and improved median OS over time. These findings support careful consideration of integrating phase I trials into treatment paradigms and highlight the ongoing necessity to address persistent disparities in trial enrollment and outcomes.