As reported in Journal of Clinical Oncology by Marth et al, the phase III European Network of Gynaecological Oncological Trial-en9/LEAP-001 study showed no significant differences in progression-free or overall survival with first-line lenvatinib/pembrolizumab vs chemotherapy in patients with advanced endometrial cancer.
Study Details
In the multicenter open-label trial, 842 patients with stage III to IV or recurrent disease and no previous chemotherapy or disease progression ≥ 6 months after neoadjuvant or adjuvant platinum-based chemotherapy were randomly assigned between May 2019 and March 2021 to receive lenvatinib at 20 mg once daily plus pembrolizumab at 200 mg every 3 weeks (n = 420; n = 320 with mismatch repair–proficient [pMMR] disease) or paclitaxel at 175 mg/m2 plus carboplatin at AUC 6 every 3 weeks (n = 422; n = 322 with pMMR disease). The primary endpoints were progression-free survival and overall survival in the pMMR population and in all patients.
Key Findings
Median time from random assignment to final analysis data cutoff (in October 2023) was 38.4 months (range = 30.3–52.9 months). In the pMMR population, median progression-free survival was 9.6 months (95% confidence interval [CI] =8.2–11.9 months) in the lenvatinib/pembrolizumab group vs 10.2 months (95% CI = 8.4–10.5 months) in the chemotherapy group (hazard ratio [HR] = 1.01, 95% CI = 0.83–1.24). Median overall survival was 30.9 months (95% CI = 25.4–37.7 months) in the lenvatinib/pembrolizumab group vs 29.4 months (95% CI = 26.2–35.4 months) in the chemotherapy group (HR = 1.02, 95% CI = 0.83–1.26). Statistical criteria for noninferiority were not met for lenvatinib/pembrolizumab in either population.
In the total population, median progression-free survival was 12.5 months (95% CI = 10.3–15.1 months) in the lenvatinib/pembrolizumab group vs 10.2 months (95% CI = 8.4–10.4 months) in the chemotherapy group (HR = 0.91, 95% CI = 0.76–1.09). Median overall survival was 37.7 months (95% CI = 32.2–43.6 months) in the lenvatinib/pembrolizumab group vs 32.1 months (95% CI = 27.2–35.7 months) in the chemotherapy group (HR = 0.93, 95% CI = 0.77–1.12).
Among all patients, grade ≥ 3 treatment-related adverse events occurred in 79% of the lenvatinib/pembrolizumab group vs 67% of the chemotherapy group. The most common events were hypertension (43%), diarrhea (8%), and proteinuria (7%) in the lenvatinib/pembrolizumab group and decreased neutrophils (26%), neutropenia (23%), and anemia (15%) in the chemotherapy group. Treatment-related adverse events led to discontinuation of any study drug in 39% vs 17% of patients. Adverse events led to death in 12 patients vs 1 patient.
The investigators concluded; “First-line [lenvatinib plus pembrolizumab] did not meet prespecified statistical criteria for [progression-free or overall survival] vs chemotherapy in pMMR [advanced endometrial cancer].”
Christian Marth, MD, PhD, AGO-Austria and Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Eisai Inc, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of all study authors, visit ascopubs.org.
