Lenvatinib Added to Pembrolizumab and Chemotherapy Fails to Improve OS in Metastatic Esophageal Squamous Cell Carcinoma
Second interim analysis results from the phase 3 LEAP-014 trial found that the addition of lenvatinib to pembrolizumab plus chemotherapy did not significantly improve survival among patients with previously untreated metastatic esophageal squamous cell carcinoma.
These data were presented by Jong-Mu Sun, MD, PhD, Samsung Medical Center, Seoul, South Korea, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
In this open-label study, 850 previously untreated patients were randomized 1:1 to receive 400 mg of pembrolizumab once every 6 weeks for up to 16 doses plus chemotherapy (investigator’s choice 5-fluorouracil and cisplatin, mFOLFOX6, or docetaxel plus cisplatin) either with (n = 423) or without (n = 427) 8 mg of daily induction lenvatinib. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response, and safety.
At analysis, median OS was 17.6 months in the lenvatinib plus pembrolizumab and chemotherapy arm and 15.5 months with pembrolizumab plus chemotherapy arm (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.77 to 1.10; P = .1852). Median PFS was 7.2 months and 6.9 months, respectively. The ORR was 62% in the lenvatinib plus pembrolizumab and chemotherapy arm and 55% in the pembrolizumab plus chemotherapy arm. As OS did not meet statistical significance, the trial was stopped early.
No new safety signals were identified. Grade ≥3 adverse events occurred in 97% of patients in both treatment arms. Grade ≥ 3 drug-related adverse events occurred in 69% and 68% of patients, respectively.
In conclusion, first-line treatment with lenvatinib plus pembrolizumab and chemotherapy did not improve OS compared to pembrolizumab plus chemotherapy alone in this patient population.
Source:
Sun J, Kim S, Ogata T, et al. Lenvatinib plus pembrolizumab and chemotherapy vs pembrolizumab and chemotherapy in untreated metastatic esophageal squamous cell carcinoma: The randomized phase 3 LEAP-014 study. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. Abstract LBA79
