Pembrolizumab Plus Lenvatinib Did Not Significantly Improve Survival for Patients With Mismatch Repair-Proficient Advanced or Recurrent Endometrial Cancer

Final Results From the LEAP-001 Study 

According to final results from the phase 3 LEAP-001 study, first-line lenvatinib plus pembrolizumab did not significantly improve survival compared to lenvatinib plus chemotherapy among patients with mismatch repair-proficient (pMMR) advanced or recurrent endometrial cancer. 

“Chemotherapy-based regimens, including in combination with immunotherapy, are a standard treatment approach as first-line therapy,” stated Christian Marth, MD, PhD, Medical University of Innsbruck, Austria, and coauthors. Here, researchers compare this standard of care regimen against “a novel chemotherapy-free combination treatment regimen.” 

In this open-label study, researchers randomized 842 patients with advanced or recurrent endometrial cancer to receive 20 mg of daily lenvatinib plus either 200 mg of pembrolizumab (pembrolizumab arm; n = 420) or paclitaxel plus carboplatin (chemotherapy arm; n = 422), once every 3 weeks. Stratification was based on mismatch repair status. Primary end points included progression-free survival (PFS) and overall survival (OS) in both the intention-to-treat and in the pMMR (pembrolizumab n = 320; chemotherapy n = 322) populations. A key secondary end point was safety. 

At final analysis, the median PFS in the pMMR population was 9.6 months in the pembrolizumab arm and 10.2 months in the chemotherapy arm. The median PFS in the intention-to-treat population was 12.5 months and 10.2 months, respectively. The median OS in the pMMR population was 30.9 months in the pembrolizumab arm and 29.4 months in the chemotherapy arm. The median OS in the intention-to-treat population was 37.7 months and 32.1 months, respectively. 

Grade ≥3 treatment-related adverse events occurred in 79% of patients in the pembrolizumab arm and 67% of patients in the chemotherapy arm. The most common events occurring in ≥ 20% of patients included hypertension, diarrhea, proteinuria, fatigue, nausea, decreased appetite, ALT increase, AST increase, arthralgia, anemia, alopecia, neutrophil count decrease, neutropenia, white blood cell count decrease, peripheral neuropathy, and peripheral sensory neuropathy. There were 10 treatment-related deaths in the pembrolizumab arm, and 2 in the chemotherapy arm. 

Lenvatinib plus pembrolizumab “did not meet the prespecified statistical criteria for PFS or OS versus paclitaxel-carboplatin,” concluded Dr Marth et al. “Despite not meeting its primary end points, evidence of meaningful antitumor activity was observed with [lenvatinib plus pembrolizumab].” 

“Negative trials are important and may inform practice as much as positive trials,” added Journal of Clinical Oncology Senior Deputy Editor Kathy Miller, MD, Indiana University Health, Indianapolis, Indiana. “The lenvatinib/pembrolizumab combination is an effective option in patients with progression on or after previous chemotherapy.” 

Source: 

Marth C, Moore RG, Bidzinski M, et al. First-line lenvatinib plus pembrolizumab versus chemotherapy for advanced endometrial cancer: A randomized, open-label, phase III trial. J Clin Oncol. Published online: November 26, 2024. doi: 10.1200/JCO-24-01326