Dr Wagar on Lenvatinib Plus Pembrolizumab vs Chemo in First-Line Advanced Endometrial Cancer

“There wasn't really a difference in overall survival [OS] outcomes between the lenvatinib [plus] pembrolizumab up-front group vs the chemotherapy up-front group. [Data] didn't meet a specific prespecified criterion for progression-free survival [PFS] or OS. [Therefore,] chemotherapy remains the standard of care, particularly for [patients with pMMR] endometrial cancer. [However], in the dMMR group, there was quite a bit of a signal [favoring] the lenvatinib plus pembrolizumab arm."

Matthew Wagar, MD, a gynecologic oncology fellow in the Department of Obstetrics and Gynecology at the University of Wisconsin School of Medicine and Public Health, discusses findings from the phase 3 LEAP-001 trial (NCT03884101) evaluating lenvatinib (Lenvima) plus pembrolizumab (Keytruda) vs chemotherapy as first-line treatment for patients with advanced endometrial cancer.

Findings demonstrated that lenvatinib plus pembrolizumab did not meet prespecified statistical criteria for progression-free survival (PFS) or overall survival (OS) superiority over chemotherapy in the mismatch repair–proficient (pMMR) population, Wagar begins. In this subgroup, the median PFS was 9.6 months (95% CI, 8.2-11.9) in the lenvatinib plus pembrolizumab arm (n = 320) vs 10.2 months (95% CI, 8.4-10.5) in the chemotherapy arm (n = 322; HR, 0.99; 95% CI, 0.82-1.21). Among all-comers, the median PFS was 12.5 months (95% CI, 10.3-15.1) with lenvatinib plus pembrolizumab (n = 420) vs 10.2 months (95% CI, 8.4-10.4) with chemotherapy (n = 422; HR, 0.91; 95% CI, 0.76-1.09).

Additionally, median OS in the pMMR population was 30.9 months (95% CI, 25.4-37.7) with lenvatinib plus pembrolizumab vs 29.4 months (95% CI, 26.2-35.4) with chemotherapy (HR, 1.02; 95% CI, 0.83-1.26). Among all-comers, the median OS was 37.7 months (95% CI, 32.2-43.6) in the lenvatinib plus pembrolizumab arm vs 32.1 months (95% CI, 27.2-35.7) in the chemotherapy arm (HR, 0.93; 95% CI, 0.77-1.12).

Notably, exploratory analysis in the mismatch repair–deficient (dMMR) population suggested a potential signal favoring lenvatinib plus pembrolizumab, leading to interest in future immunotherapy-first strategies for dMMR advanced endometrial cancer, Wagar explains. This approach may offer a means to delay chemotherapy and preserve platinum-based treatments for later disease progression, he adds.

These findings confirm that chemotherapy remains the standard of care for pMMR advanced endometrial cancer, and further investigation into immunotherapy-based strategies for dMMR patients is warranted, Wagar concludes.