A phase II, randomized, double-blind study of the use of rucaparib vs. placebo maintenance therapy in metastatic and recurrent endometrial cancer.

Objective: Rucaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor with proven efficacy in multiple tumor types. The efficacy of PARP inhibition in endometrial cancer remains unclear.

Methods: We conducted a multi-institutional, double-blind, placebo-controlled, randomized phase II trial. Eligible patients had stage III, IV or recurrent endometrial cancer. We assigned patients with measurable, or non-measurable disease following completion of first- or second-line chemotherapy in a 1:1 ratio to receive oral rucaparib (600 mg twice daily) or placebo until disease progression. The primary endpoint was progression-free survival. Secondary outcomes were overall survival and safety. Exploratory outcomes evaluated response in relation to tumor molecular profiles and transcriptomic profiles.

Results: 79 patients were randomized, 39 received rucaparib and 40 received placebo. Median progression free survival was 28.1 months in the rucaparib arm compared to 8.7 months in the placebo group, hazard ratio 0.45; (95 % confidence interval [CI] (0.24-0.87); p = 0.02). Median overall survival was not reached in the rucaparib arm compared to 28.4 months in the placebo arm; hazard ratio 0.43 (95 % CI, 0.18-1.05). In patients treated with rucaparib, the most common grade ≥ 3 adverse events were anemia, fatigue, and neutropenia. Loss of p53 activity correlated to improved rucaparib response by transcriptomic evaluation. Traditional DNA repair homologous recombination biomarkers did not correlate with response.

Conclusions: Maintenance use of rucaparib after first- or second-line chemotherapy demonstrates promising activity and warrants further evaluation in a phase III evaluation. Adverse events were aligned with previous use of rucaparib in other tumor types and no new safety signals were identified.

Clinicaltrials: gov identifier: NCT03617679.