Lenvatinib (VEGFR/FGFR TKI) + pembrolizumab (PD-1) improves OS/PFS after (neo)adjuvant platinum in endometrial cancer

Lenvatinib is an oral multi-kinase antiangiogenic TKI (VEGFR1–3/FGFR1–4, etc.) combined with pembrolizumab, a PD-1 inhibitor, and was analyzed in two Phase 3 randomized trials restricted to patients whose only prior systemic therapy was (neo)adjuvant platinum: Study 309/KEYNOTE-775 (post-progression setting; n=300 in this subgroup) and ENGOT-en9/LEAP-001 (frontline/recurrent ≥6 months after (neo)adjuvant platinum; n=121 in this subgroup). In KEYNOTE-775, lenvatinib+pembrolizumab improved median OS to 17.4 vs 13.3 months (HR 0.67) and median PFS to 7.2 vs 3.9 months (HR 0.52), with ORR 34.3% vs 16.6% (chemo was doxorubicin or paclitaxel—historically ~10–30% ORR in pretreated EC, broadly consistent with the 16.6% seen here). In LEAP-001, median OS was 35.4 vs 22.1 months (HR 0.66; CI crossed 1.0), median PFS 15.0 vs 8.3 months (HR 0.52), and ORR 63.5% vs 43.1% versus carboplatin/paclitaxel; common TRAEs with lenvatinib+pembrolizumab included hypertension (62.4%/60.3%) and hypothyroidism (58.2%/60.3%)—toxicities not typical of carbo/taxol and often dose-management–driven.