PARP Inhibitor Rucaparib Extends PFS to 28 mo in Metastatic/Recurrent Endometrial Cancer

Rucaparib, an oral PARP1/2 inhibitor that exploits tumor DNA-repair defects, was tested as switch-maintenance after 1–2 chemotherapy lines in a double-blind Phase II trial (NCT03617679). Seventy-nine patients with stage III/IV or recurrent endometrial cancer were randomized 1:1 to rucaparib 600 mg BID or placebo until progression. Median PFS leapt to 28.1 months with rucaparib versus 8.7 months on placebo (HR 0.45, p = 0.02), and overall survival was not yet reached versus 28.4 months (HR 0.43). Grade ≥3 anemia, fatigue, and neutropenia were the main toxicities—consistent with prior ovarian-cancer experience—without new safety signals. Placebo PFS mirrors real-world outcomes (~10.8 mo), while rucaparib’s 28-month duration dwarfs the 5.7 month PFS reported for selinexor maintenance, underscoring PARP potency even though classical HR-deficiency biomarkers were non-predictive; transcriptomic loss of p53 activity, however, tracked benefit.