Lenvatinib/Pembrolizumab Benefit Maintained in Advanced Endometrial Cancer

Vicky Makker, MD

After extended follow-up, continued benefit was seen with the combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) in patients with advanced endometrial cancer who previosuly received platinum chemotherapy, updated efficacy and safety findings from the phase 3 Study 309/KEYNOTE-775 trial (NCT03517449) showed.

Findings from the trial were presented at the 2022 European Society for Medical Oncology Congress and showed that lenvatinib/pembrolizumab improved progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) over treatment of physician’s choice in patients with advanced endometrial cancer, regardless of mismatch repair (MMR) status.

“Consistent with the interim analysis results, at the final pre-specified [OS] analysis, lenvatinib plus pembrolizumab continued to demonstrate clinically meaningful improvements in OS, PFS, and ORR versus chemotherapy in pMMR and all-comer patients with advanced endometrial cancer who received prior platinum therapy, supporting the robustness of the treatment effect that was observed at the interim analysis,” lead author Vicky Makker, MD, an associate attending physician at Memorial Sloan Kettering Cancer Center, said in a presentation of the data.

The trial included 827 patients, of whom 697 were MMR proficient (pMMR) and 130 were MMR deficient (dMMR). To be eligible, patients were required to have experienced disease progression after a prior systemic, platinum-based chemotherapy regimen and have an ECOG performance status of 0 or 1.

Participants were randomly assigned to receive either lenvatinib plus pembrolizumab (n = 411) or treatment with physicians’ choice of intravenous doxorubicin at 60 mg/m² every 3 weeks or paclitaxel at 80 mg/m² intravenously for 3 weeks on and 1 week off (n = 416). Median follow-up was 18.7 months for those randomized to the lenvatinib/pembrolizumab arm, and 12.2 months for the physicians’ choice arm.

Median PFS was longer in the doublet arm for all patients on the study, at 7.3 months (95% CI, 5.7-7.6) and 3.8 months (95% CI, 3.6-4.2) in the lenvatinib/pembrolizumab arm and physicians’ choice arms, respectively. The drug combination also led to an improved median PFS in the pMMR group, at 6.7 months (95% CI, 5.6-7.4) months vs 3.8 months (95% CI, 3.6-5.0), respectively.

Median OS was also longer in the lenvatinib/pembrolizumab arm for all-comers compared with the physicians’ choice at 18.7 months (95% CI, 15.6-21.3) vs 11.9 months (95% CI, 10.7-13.3), respectively. For patients with pMMR advanced endometrial cancer, median OS was slightly longer and still favored lenvatinib plus pembrolizumab at 18.0 months (95% CI, 14.9-20.5) and 12.2 months (95% CI, 11.0-14.1), respectively.

Of note, 10% of patients with pMMR disease and 8.7% of the entire study population randomized to receive physicians’ choice treatment ended up receiving subsequent treatment with lenvatinib plus pembrolizumab.

The median ORR was 33.8 months (95% CI, 29.3-38.6) for all comers in the lenvatinib/pembrolizumab arm and 14.7 months (95% CI, 11.4-18.4) in the physicians’ choice group. For those with pMMR advanced endometrial cancer, ORR was 32.4 months (95% CI, 27.5-37.6) and 15.1 months (95% CI, 11.5-19.3) in the investigational and physicians’ choice arms, respectively.

“Treatment-emergent adverse events were also consistent with the primary analysis,” Makker noted.

Grade 3 or higher adverse events (AEs) occurred in 79% of patients treated with lenvatinib plus pembrolizumab compared with 60% of patients in the chemotherapy arm. The most common grade 3 or higher AEs for those on the lenvatinib/pembrolizumab arm were hypertension (39%), weight loss (11%), diarrhea (>10%), and decreased appetite (>10%).

Seventy-two percent of patients on the lenvatinib/pembrolizumab arm had a treatment interruption. Sixty-seven percent of patients had a dose reduction for lenvatinib, with the drug being discontinued in 36% of patients. Twenty-two percent of patients discontinued treatment with pembrolizumab and 16% of patients discontinued both drugs.

“These results continue to support the use of lenvatinib plus pembrolizumab as a standard therapy in patients with previously treated advanced endometrial cancer,” Makker concluded.

_Reference

_{Makker V, Colombo N, Casado Herraez A, et. al. Updated efficacy and safety of lenvatinib (LEN) + pembrolizumab (pembro) vs treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): study 309/KEYNOTE-775. Ann Oncol. 2022;33(suppl 7):525MO. doi:10.1016/annonc/annonc1054}