BERLIN — Adding the antiangiogenic lenvatinib to standard first-line therapy does not prolong the lives of patients with metastatic esophageal squamous cell carcinoma, according to a second interim analysis from the phase 3 LEAP-014 trial.

The trial, which evaluated the addition of lenvatinib (Lenvima) to standard pembrolizumab and chemotherapy, found no overall survival benefit over 22 months compared to standard care alone.

The trial was stopped early as overall survival was unlikely to reach statistical significance at the final analysis, investigator Jong-Mu Sun, MD, PhD, Sungkyunkwan University School of Medicine, Seoul, Korea, told attendees at the European Society for Medical Oncology (ESMO) Annual Meeting 2025.

Although lenvatinib plus pembrolizumab has been approved for advanced renal cell carcinoma and advanced endometrial carcinoma, the combination did not meet its primary endpoint in metastatic esophageal squamous cell carcinoma and, “therefore, lenvatinib has no role in this disease,” said Jaffer A Ajani, MD, University of Texas MD Anderson Cancer Center, Houston, who was not involved in the trial.

In LEAP-014, 850 patients with previously untreated metastatic esophageal squamous cell carcinoma were randomized to a control group receiving pembrolizumab (400 mg every 6 weeks) plus chemotherapy or an experimental arm that added lenvatinib (8 mg daily) to this regimen during a 12-week induction phase, followed by a consolidation phase of lenvatinib (20 mg daily) plus pembrolizumab and no chemotherapy.

Lenvatinib was continued until disease progression or unacceptable toxicity, whereas pembrolizumab was administered for a maximum of 2 years.

At a median follow-up of 22 months, 326 patients in the lenvatinib arm and 333 in the control arm had discontinued treatment, mostly due to progression or adverse events. Median overall survival duration was 17.6 months and 15.5 months in the lenvatinib and control arms, respectively (hazard ratio [HR], 0.92, P =.185).

Similarly, there was no difference between the groups in terms of progression-free survival: 7.2 months with the addition of lenvatinib compared with 6.9 months without it (HR, 0.89; P = .075).

Regarding safety, both treatment groups had similar rates of grade 3 or greater treatment-related adverse events: 81.2% in the lenvatinib arm and 79.1% in the control arm. Decreased neutrophil count, nausea, diarrhea, and anemia were among the most common adverse events of any grade. 

In comments to Medscape Medical News, Ajani noted that the trial did not measure biomarkers related to lenvatinib, either in blood or tissue. He suggested that having a better understanding of whether patients’ response to lenvatinib is tied to specific biomarkers would be important.

The study was funded by Merck Sharp & Dohme LLC. Sun disclosed having financial and institutional ties with and receiving research funding from Merck Sharp & Dohme. Ajani declared being an ad hoc advisor to Merck.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.