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

Abstract

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. 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. 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 (<i>P</i> &lt; .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. 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.