Dr Corr on the Rationale for Investigating Rucaparib Maintenance in Endometrial Cancer

Bradley R. Corr, MD, associate professor, LeBert Suess Family Endowed Professor in Ovarian Cancer Research, gynecologic oncology team, the University of Colorado Anschutz Medical Campus, discusses the rationale for and findings from a phase 2 study (NCT03617679) evaluating the use of maintenance therapy with rucaparib (Rubraca) vs placebo in patients with metastatic and recurrent endometrial cancer.

The use of PARP inhibitors has expanded across several tumor types, including breast, ovarian, and prostate cancers. These agents are particularly beneficial for patients with BRCA mutations or homologous recombination–deficient disease, Corr says. However, preclinical data show that differential DNA activity may be present in endometrial cancer, which is typically a mutation-driven disease, Corr explains. Based on these preclinical findings, Corr and colleagues launched a phase 2 trial of rucaparib vs placebo maintenance therapy in patients with metastatic or recurrent endometrial cancer who had received 1 to 2 prior lines of cytotoxic chemotherapy.

In the intent-to-treat population, this study showed a median progression-free survival (PFS) of 28.1 months (95% CI, 12.8-not yet reached [NR]) in the rucaparib arm (n = 39) vs 8.7 months (95% CI, 5.4-16.7) in the placebo arm (n = 40), translating to a 19.4 month PFS improvement with the PARP inhibitor vs placebo (HR, 0.45; 95% CI, 0.26-0.80; P = .005), Corr notes. In a subgroup analysis ofpatients with stage III or IV disease, the median PFS was 21.1 months (95% CI, 6.8-NR) with rucaparib (n = 28) vs 9.2 months (95% CI, 5.4-18.4) with placebo (n = 30; HR, 0.52; 95% CI, 0.27-1.01; P = .049). Among patients with recurrent disease, the median PFS was 28.5 months (95% CI, 13.5-NR) with rucaparib (n = 11) vs 7.6 months (95% CI, 2.3-NR) with placebo (n = 10; HR, 0.33; 95% CI, 0.11-1.03; P = .046). These findings hold significant implications for patients with metastatic and recurrent endometrial cancer, Corr concludes.