Efficacy and Safety of Investigational Treatments in Contemporary Early-Phase Clinical Trials for Japanese Gynecologic Cancers: A Single-Institution Retrospective Analysis

PURPOSE Therapeutic options for advanced gynecologic cancers remain limited after standard therapy failure. Contemporary early-phase clinical trials (EPCTs) investigating modern agents may offer benefit, yet Asian patients are underrepresented. We evaluated the efficacy and safety of contemporary EPCTs in Japanese patients and examined the role of biomarker-based selection. METHODS This single-institution retrospective cohort consecutively enrolled patients with advanced gynecologic cancers treated in phase I/II trials (April 2016 to March 2024). For patients who enrolled in more than one trial, only the first EPCT was evaluated. Biomarker selection used genomic, protein, or histology criteria. End points included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS A total of 144 patients were included in this study. The overall ORR was 23.6% and was higher with biomarker-based selection (33.3% v 12.1%; P = .003). The median PFS was 3.6 months overall and longer with biomarker-based selection (5.6 v 2.6 months; hazard ratio, 0.54 [95% CI, 0.38 to 0.76]; P < .001). The median OS was 13.0 months. Grade ≥3 treatment-related adverse events occurred in 18.1%, serious adverse events in 7.6%, and one treatment-related death (0.7%). CONCLUSION In this retrospective single-institution cohort, contemporary EPCTs may offer clinically meaningful activity with manageable toxicity for Japanese patients with gynecologic cancers. Biomarker-based selection was associated with higher ORR and longer PFS, but not with a significant OS difference; these findings should be interpreted cautiously, given residual confounding, and require prospective validation.