A Phase II, Randomized, Double-blind, Study of the Use of Rucaparib vs. Placebo Maintenance Therapy in Metastatic and Recurrent Endometrial Cancer

SGO Annual Meeting on Women's Cancer 2024 Presentation
Authors Bradley R. Corr, Ashley Haggerty, Stefan M. Gysler, Sarah Taylor, Kian Behbakht, Jill Alldredge, Carolyn Lefkowits, Lindsay W. Brubaker, Catherine Bouts, Lisa Marie Babayan, Samantha Hopp, Junxiao Hu, Saketh R. Guntupalli

Objectives: There is convincing rational to consider PARP inhibition therapy in endometrial cancer. Similar to their use in other malignancies, targeting DNA repair mechanisms can be effective in endometrial cancer. However, the pathway to DNA repair deficiencies may be different. We hypothesized that the use of maintenance rucaparib will have therapeutic benefit for patients with metastatic and recurrent endometrial cancer.

Methods: This was a multi-institutional, randomized, placebo controlled, maintenance trial for patients with metastatic/recurrent endometrial cancer with 1-2 prior lines of therapy who demonstrated a complete (CR) or partial response (PR) after prior chemotherapy. Randomization was 1:1 for rucaparib (600mg PO BID) to placebo. Treatment occurred on a 28-day cycle until progression, intolerance, or completion of trial. Stratification of treatment arms occurred for histology, number of prior lines of therapy, and response to prior therapy. Primary endpoint was progression free survival (PFS) with secondary endpoint of overall survival (OS). Exploratory analyses were performed based on molecular profiling by immunohistochemistry (IHC) and next generation sequencing (NGS).

Results: Seventy-nine patients were randomized with a median follow up of 25.3 months (IQR 19.3-40.3). The majority (59.5%) of patients had a CR from prior line of therapy. Most (73.4%) were treated after adjuvant therapy. Less than half (44.3%) of patients had previously received radiation. Tumor classification was 0% POLE, 51.9% p53mut, 10.1% dMMR, 20.3% NSMP, and 17.7% missing at time of abstract submission. BRCA, HRD, and updated complete molecular data to be provided at time of presentation. In the intention to treat (ITT) population median PFS was 28.1 vs 8.7 months (rucaparib vs placebo) (HR 0.45; 95%CI 0.26-0.80, p=0.005). Median OS was NR vs 28.4 months (rucaparib vs placebo) (HR 0.48; 95%CI 0.23-1.03, p=0.055). Exploratory PFS analysis based on stratification factors favors rucaparib to placebo for patient with PR to prior therapy (HR 0.23; 95%CI 0.1-0.54, P<0.0001), and following adjuvant therapy (HR 0.52; 95%CI 0.27-1.01, p=0.049) or recurrent therapy (HR 0.33; 95%CI 0.11-1.03, p=0.046). Treatment following CR to prior therapy demonstrates HR 0.49 (95%CI 0.22-1.13). Safety profile of rucaparib was similar to previously reported studies with grade 3/4 TRAE’s occurring in 35.9% of the rucaparib arm, most common being anemia (20.5%), fatigue (7.7%), thrombocytopenia (7.7%), and neutropenia (7.7%).

Conclusions: Maintenance use of rucaparib after first or second line chemotherapy improves PFS for patients with metastatic and recurrent endometrial cancer in a statistically significant and clinically impactful manner.