Lenvatinib (LEN) plus pembrolizumab (PEMBRO) for early-line treatment of advanced/recurrent endometrial cancer (EC).

Background: As part of an ongoing phase Ib/II study (NCT02501096) in patients (pts) with selected solid tumors, LEN (20 mg PO QD) + PEMBRO (200 mg IV Q3W) displayed substantial and durable antitumor activity in advanced EC. In previously treated EC that was not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR; n=94 pts), the objective response rate (ORR) by independent imaging review (IIR) per RECIST 1.1 was 38.3% (95% CI 28.5–48.9). In this post hoc analysis, we assessed 2 subgroups of pts with previously treated, advanced, non MSI-H or dMMR EC who received LEN + PEMBRO in an early-treatment setting. Methods: Pts were examined in 2 subgroups: (1) Pts with only 1 prior line of cytotoxic therapy regardless of surgical stage or setting (adjuvant treatment for local-regional disease or treatment for metastatic disease); and (2) pts from subgroup 1 with local-regional disease at diagnosis who received only adjuvant cytotoxic therapy. There were no restrictions on prior hormonal or chemoradiation therapies in either subgroup. Tumor responses were assessed by IIR per RECIST 1.1. Results: Subgroup 1 included 63 pts and subgroup 2 had 21 pts. ORR (95% CI) was 41.3% (29.0–54.4) for subgroup 1 and 57.1% (34.0–78.2) for subgroup 2. Additional efficacy outcomes are summarized in the table. In subgroup 1, treatment-related adverse events (TRAEs) occurred in 62 (98%) pts (42 [67%] ≥ grade 3). TRAEs led to study-drug interruption of one or both drugs in 43 (68%) pts and dose reductions of LEN in 42 (67%) pts; 12 (19%) pts discontinued one or both drugs due to a TRAE. Serious TRAEs occurred in 18 (29%) pts and 2 (3%) pts died from a TRAE. The safety profile for subgroup 2 was generally similar to the profile for subgroup 1. Conclusions: The efficacy of LEN + PEMBRO for early-line treatment of advanced non MSI-H or dMMR EC appears promising. No new safety signals have emerged. A phase III study of LEN + PEMBRO vs paclitaxel + carboplatin for first-line treatment in advanced or recurrent EC is underway. Clinical trial information: NCT02501096.