Lenvatinib-Pembrolizumab Combo Misses Survival Endpoints in Endometrial Cancer Trial

The phase III LEAP-001 trial, presented at the Society of Gynecologic Oncology annual meeting, evaluated the efficacy of lenvatinib (Lenvima) combined with pembrolizumab (Keytruda) against chemotherapy for first-line treatment of advanced or recurrent endometrial cancer. The study involved 842 patients and found that the combination did not significantly improve progression-free survival (PFS) or overall survival (OS) compared to chemotherapy in the overall population. Specifically, median PFS was 12.5 months for the combination versus 10.2 months for chemotherapy, and median OS was 37.7 months versus 32.1 months, respectively.

However, the combination showed improved outcomes in certain subgroups. Patients with deficient mismatch repair (dMMR) disease experienced a median PFS of 31.8 months with the combination versus 9 months with chemotherapy, and the median OS was not reached in either arm. Additionally, patients who had received prior neoadjuvant/adjuvant chemotherapy saw improved PFS in both the proficient mismatch repair (pMMR) population and the overall population.

The trial also noted a higher overall response rate (ORR) in the dMMR population (72% vs. 58%) and better ORR and duration of response in the prior neoadjuvant/adjuvant chemotherapy subgroup. Despite these promising results in specific groups, the combination was associated with a higher rate of adverse events (AEs) leading to treatment interruption and discontinuation compared to chemotherapy.

Christian Marth, MD, PhD, of Innsbruck Medical University, emphasized that while the trial did not meet its primary endpoint, the combination of lenvatinib and pembrolizumab remains an important treatment option for advanced/recurrent endometrial cancer, particularly for patients with pMMR disease who have progressed during prior systemic therapy.