Abemaciclib (CDK4/6 inhibitor) + hormonal therapy posts 17.5-mo mPFS in recurrent LGSOC, biomarker-enriched benefit in NSMP ER+ endometrial cancer

Abemaciclib is an oral CDK4/6 inhibitor given at 150mg BID with hormonal therapy in a single-center Phase II study enrolling ER+ recurrent endometrial cancer (EC), low-grade serous ovarian cancer (LGSOC), and selected high-grade serous ovarian cancer (HGSOC) with CDK4/6-activation features (NCT04469764); 43 patients were evaluable (EC n=21; LGSOC n=14; HGSOC n=8) with median 3 prior lines and 29-month median follow-up (data cutoff December 2, 2025). In ER+ EC, 24-week PFS was 56.1%, mPFS 9.0 months, DCR 63%, and ORR 21% (1 CR), with activity concentrated in NSMP tumors (mPFS 10.4 vs 1.9 months in non-NSMP; p=0.02; all responses in NSMP); exploratory CTNNB1-mut cases had numerically longer mPFS (10.4 vs 5.2 months; p=0.22). In LGSOC, 24-week PFS was 71.4%, mPFS 17.5 months, DCR 79%, and ORR 14% with notable durability (28% on treatment >3 years; longest ongoing at 4.6 years), while HGSOC did poorly despite “CDK4/6 activating mutations” (mPFS 1.6 months); no new safety signals were reported—benchmarked against recurrent LGSOC SOC where trametinib delivers mPFS ~13.0 months vs physician’s-choice SOC ~7.2 months (GOG-281/LOGS), this 17.5-month mPFS is directionally competitive but needs randomized confirmation, and for recurrent EC endocrine-targeted options like everolimus+letrozole have reported mPFS ~3.0 months (single-arm) to ~6 months (randomized phase II) with ORR ~22% (making this EC signal plausibly additive, especially in NSMP).