Systemic therapy for endometrial cancer...Preferred regimen...Lenvatinib/pembrolizumab (category 1) for non-MSI-high [MSI-H]/non-MMR-deficient [dMMR] tumors

OS was significantly longer with LEN + pembro vs TPC in pMMR aEC (median 17.4 vs 12.0 mo; HR 0.68) and in all-comers (median 18.3 vs 11.4 mo; HR 0.62). ORR was significantly greater with LEN + pembro vs TPC in pMMR aEC (30.3% vs 15.1%) and in all-comers (31.9% vs 14.7%).

LEN+pembro improved PFS, OS, and ORR vs TPC in patients with dMMR aEC, with a manageable safety profile generally consistent with all-comers and previous studies.

The study met the dual primary endpoints of progression-free survival (PFS), as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and overall survival (OS) as well as the secondary efficacy endpoint of objective response rate (ORR), as assessed by BICR per RECIST v1.1, in the all-comer population (mismatch repair proficient [pMMR] and mismatch repair deficient [dMMR]) and in the pMMR subgroup...A statistically significant and clinically meaningful improvement in PFS was seen in the all-comer population, in which KEYTRUDA plus LENVIMA (n=411) reduced the risk of disease progression or death by 44% (HR=0.56 [95% CI: 0.47-0.66]; p<0.0001), with a median PFS of 7.2 months (95% CI: 5.7-7.6; number of events=281) versus 3.8 months (95% CI: 3.6-4.2; number of events=286) for patients who received chemotherapy (treatment of physician’s choice [TPC] of doxorubicin or paclitaxel; n=416).

The ORRWk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORRWk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94)...Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma...