Can we learn from failures? A systematic review of phase III trials in platinum-resistant ovarian cancer

This systematic review analyzed phase III trials in platinum-resistant ovarian cancer to understand their poor outcomes and guide future trials. A systematic review adhering to PRISMA guidelines was conducted. PubMed/Medline, Cochrane Library CENTRAL, and EMBASE were searched for randomized phase III trials (2010-January 2024) involving patients with platinum-resistant ovarian cancer. Fifteen studies (5,468 patients) were included. Platinum resistance was defined by the interval between last platinum administration and recurrence/progression. Heterogeneity existed in defining platinum-refractory patients. Experimental arms included chemotherapy (4 trials), immune checkpoint inhibitors, anti-angiogenic agents, targeted agents, or antibody-drug conjugates (2 trials each), and others (3 trials). Control arms consistently used single-agent chemotherapy (paclitaxel, gemcitabine, pegylated liposomal doxorubicin, or topotecan). Only four trials had biomarker-selected populations. Most trials (except TRINOVA1, AURELIA, and MIRASOL) showed no progression-free survival benefit. Only MIRASOL had statistically significant overall survival improvement. Negative outcomes likely stem from various factors, including inconsistent platinum resistance definitions, inadequate control arm benchmarks, and suboptimal biomarker use. A deeper understanding of tumor biology and its integration into trial design is crucial to enhance drug development in this patient population, aiming for improved efficacy while preserving quality of life.