Rucaparib Maintenance Therapy Displays Activity in Pretreated Recurrent/Metastatic Endometrial Cancer

Maintenance therapy with rucaparib (Rubraca) demonstrated activity for the treatment of patients with recurrent or metastatic endometrial cancer following the completion of first- or second-line chemotherapy, according to findings from a phase 2 study (NCT03617679) published in Gynecologic Oncology.1

At a median follow-up of 25 months (IQR, 19.3-40.3), results from the study showed that patients who received rucaparib (n = 39) achieved a median progression-free survival (PFS) of 28.1 months (95% CI, 12.8-not reached [NR]) compared with 8.7 months (95% CI, 5.4-16.7) among patients who received placebo (n = 40; HR, 0.45; 95% CI, 0.24-0.87; P = .02). The median overall survival (OS) was NR (95% CI, 34.8 months-NR) vs 28.4 months (95% CI, 19.0-NR), respectively (HR, 0.43; 95% CI, 0.18-1.05).

“…The use of rucaparib maintenance therapy in advanced or recurrent endometrial cancer following standard systemic chemotherapy reduces the risk of disease progression or death by 55% compared [with] placebo,” Bradley R. Corr, MD, the LeBert Suess Family Endowed Professor in Ovarian Cancer Research and an associate professor of gynecologic oncology at the University of Colorado Anschutz Medical Campus in Aurora, and his coauthors wrote in the publication. “[These] positive data [reveal] that the use of rucaparib PARP inhibition in endometrial cancer should be explored further in future clinical trial evaluation.”

Rucaparib is a PARP inhibitor that has demonstrated proven efficacy in multiple tumor types, but its activity in patients with endometrial cancer has historically been unclear. In April 2018, the FDA approved rucaparib for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.2 The approval was supported by data from the phase 3 ARIEL3 trial (NCT01968213), which demonstrated that patients who received rucaparib experienced a significant PFS benefit compared with those who received placebo (HR, 0.36; 95% CI, 0.30-0.45; P = .0001).

What Were the Key Design and Baseline Characteristics?

The multi-institutional, double-blind, placebo-controlled, randomized phase 2 study enrolled patients with stage III or IV or recurrent endometrial cancer who had received 1 or 2 prior lines of cytotoxic chemotherapy; the primary chemotherapy regimen must have consisted of at least 4 and no more than 8 completed cycles.3 In order to be eligible for the study, patients also needed to be 18 to 89 years old, have an ECOG performance status of 0 to 2 and have adequate laboratory values. Those who received radiation to the whole pelvis or at least 50% of the spine were required to have completed radiation therapy and have at least 4 weeks elapse prior to the initiation of study treatment.

Patients were randomly assigned 1:1 to receive rucaparib at 600 mg twice daily or placebo.1 Treatment was administered via 28-day cycles and was intended to be a maintenance therapy that would be initiated within 8 weeks of the last dose of prior therapy. Therapy continued until disease progression or another indication for discontinuation was reported.

The primary end point was PFS. Secondary end points included OS and the incidence of treatment-emergent adverse effects (AEs).

At baseline, the median ages in the investigational and placebo arms were 66 years (IQR, 61-72) and 67 years (IQR, 58-71), respectively. Most patients in both arms were White (84.6% vs 85%), non-Hispanic (89.7% vs 95%), had an ECOG performance status of 0 (66.7% vs 70%), had endometrioid histology (51.3% vs 52.5%), had received 1 prior line of therapy (74.4% vs 77.5%), and had no residual disease following prior chemotherapy (53.8% vs 65%).

What Were the Subgroup Efficacy Data and the Safety Findings?

Findings from a subgroup analysis showed that patients who received 2 prior lines of therapy in the rucaparib arm (n = 10) experienced a significant PFS benefit compared with those in the placebo arm (n = 9; HR, 0.14; 95% CI, 0.04-0.49). Notably, patients who were being treated following disease recurrence (HR, 0.23; 95% CI, 0.09-0.56), those with residual disease at baseline (HR, 0.23; 95% CI, 0.10-0.54), those with endometrioid disease (HR, 0.32; 95% CI, 0.13-0.82), those with abnormal p53 (HR 0.56; 95% CI, 0.8-1.11), and those with PTEN-mutated disease (HR, 0.32; 95% CI, 0.09-1.11) had significant PFS benefits with rucaparib vs placebo.

In terms of safety, the most common any-grade AEs in the investigational and control arms included nausea (59% vs 22.5%), fatigue (53.8% vs 25%), and anemia (48.7% vs 20%). Any-grade treatment-related AEs (TRAEs) were reported in 95% and 67.5% of patients, respectively; grade 3 or higher TRAEs occurred at respective rates of 36% and 7.5%. Dose interruptions (36% vs 5%), reductions (33% vs 5%), and discontinuations (8% vs 2.5%) due to TRAEs were present in both arms. Notably no treatment-related deaths were reported.

“This trial concludes that the use of rucaparib maintenance therapy after first- or second-line chemotherapy in advanced and recurrent endometrial cancer patients provides a statistically and clinically meaningful improvement in the reduction of risk of progression of disease and rucaparib maintenance is a safe and tolerable therapy... we acknowledge that this data is not a guarantee of clinical benefit, and future evaluation with phase 3 analysis is warranted to confirm efficacy,” Corr and his coauthors wrote in their conclusion.

References

1. Corr BR, Haggerty A, Gysler SM, et al. A phase II, randomized, double-blind study of the use of rucaparib vs. placebo maintenance therapy in metastatic and recurrent endometrial cancer. Gynecol Oncol. 2025;200:58-67. doi:10.1016/j.ygyno.2025.07.008
2. FDA approves rucaparib for maintenance treatment of recurrent ovarian, fallopian tube, or primary peritoneal cancer. FDA. April 6, 2018. Accessed October 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rucaparib-maintenance-treatment-recurrent-ovarian-fallopian-tube-or-primary-peritoneal
3. Rucaparib vs placebo maintenance therapy in metastatic and recurrent endometrial cancer. ClinicalTrials.gov. Updated February 11, 2025. Accessed October 14, 2025. https://clinicaltrials.gov/study/NCT03617679