Retrospective cohort study of participation of patients with gynecologic cancer in phase 1 clinical trials

Phase 1 trials are intended to define the safety of novel therapeutics, yet they offer alternative options long before these therapeutics are approved. A retrospective cohort study at two National Cancer Institute-designated Comprehensive Cancer Centers assessed efficacy, toxicities, and prognostic factors in phase 1 trials in advanced gynecologic maligancies between 2000 and 2022. A total of 335 patients were included. The mean age was 58.8 years (SD 11.5), and the median number of prior lines of therapy was three. The clinical benefit rate among response-evaluable patients was 56.2%, primarily driven by stable disease. The median overall survival (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<0.0001). 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. The authors conclude that phase 1 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 1 trials into treatment paradigms, and highlight the ongoing necessity to address persistent disparities in trial enrollment and outcomes.