Lenvatinib/Pembrolizumab Achieved Promising Survival in Advanced Endometrial Cancer

Patients with advanced endometrial cancer derived a more notable survival benefit after being treated with lenvatinib and pembrolizumab compared with chemotherapy alone.

Treatment with lenvatinib (Lenvima) plus pembrolizumab (Keytruda) led to a significantly improved survival benefit for patients with advanced endometrial cancer compared with chemotherapy alone, according to results from the phase 3 KEYNOTE-775 trial (NCT03517449).

Patients in the lenvatinib cohort had a median progression-free survival (PFS) of 6.6 months compared with 3.8 months in the chemotherapy cohort (HR, 0.60; 95% CI, 0.50-0.72; P <.001) in the mismatch repair–proficient (pMMR) population. In the overall population, the median PFS was 7.2 and 3.8 months, respectively (HR, 0.56; 95% CI, 0.47-0.66; P <.001). Investigators also reported a median overall survival (OS) in the pMMR population of 17.4 months among those treated with the lenvatinib combination vs 12.0 months in those treated with chemotherapy (HR, 0.68; 95% CI, 0.56-0.84; P <.001). In the overall population, the median OS was 18.3 months and 11.4 months in the experimental and control groups, respectively (HR, 0.62; 95% CI, 0.51-0.75; P <.001).

“This trial showed that treatment with lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy of the treating physician’s choice, both in the pMMR population and in the overall trial population of patients with advanced endometrial cancer who had disease progression after the receipt of previous systemic platinum-based therapy,” the investigators wrote.

In this multicenter, open-label trial, patients were randomized 1:1 to receive either lenvatinib and pembrolizumab or physician's choice of chemotherapy. In the experimental arm, patients received 20 mg of oral lenvatinib once daily and 200 mg of intravenous pembrolizumab every 3 weeks. Patients could receive up to 35 doses of pembrolizumab. In the control arm, patients were treated with 60 mg of doxorubicin per square meter of body surface area every 3 weeks or 80 mg of paclitaxel per square meter of body surface area per week with a 3 weeks on, 1 week off treatment schedule. Patients were stratified based on ECOG performance status, region, and history of pelvic irradiation.

The study's primary end points were PFS by blinded independent central review and OS, with key secondary end points including objective response, safety, and health-related quality of life (HRQOL).

A total of 827 patients were randomized across 167 sites in 21 countries. The study had a median follow-up of 12.2 months in the lenvatinib group and 10.7 months in the chemotherapy group. The population included in the study was reflective of real-world populations. Investigators reported that 84.2% and 84.4% of patients in the experimental and control groups, respectively, were confirmed as being pMMR. Moreover, 35.0% and 38.2% of patients in both respective groups underwent prior systemic adjuvant or neoadjuvant therapy.

Additional findings from the study indicated that within the pMMR group, 30.3% of those treated with the lenvatinib combination and 15.1% of patients treated with chemotherapy had an objective response. Within the overall study population, objective responses were reported in 31.9% and 14.7% of patients, respectively. In total, among those in the pMMR subgroup, 5.2% of patients in the lenvatinib group and 2.6% of patients in the chemotherapy group experienced a complete response.

The median duration of response (DOR) was 9.2 months (range, 1.6-23.7) and 5.7 months (range, 0.0-24.2) in the lenvatinib and chemotherapy cohorts within the pMMR population, respectively. In the overall population, the DORs were 14.4 months and 5.7 months, respectively.

The most common any grade adverse effects (AEs) in the lenvatinib arm included hypertension (64.0%), hypothyroidism (57.4%), diarrhea (54.2%), and nausea (49.5%). Any grade AEs for the chemotherapy arm were nausea (46.1%), fatigue (27.6%), vomiting (20.9%), and diarrhea (20.1%). Common grade 3 or higher AEs in the lenvatinib/pembrolizumab cohort included hypertension (37.9%), weight decrease (10.3%), and decreased appetite (7.9%) compared with fatigue (3.1%), vomiting (2.3%), and diarrhea (2.1%) in the chemotherapy cohort. In total, 5.7% and 4.9% of patients in the lenvatinib and chemotherapy arms, respectively, experienced grade 5 AEs.

For HRQOL, investigators reported that over 95% of patients across both treatment groups completed the baseline QLQ-C30. No notable differences were observed between the groups.


Makker V, Colombo N, Casado A, et al. Study 309–KEYNOTE-775 Investigators. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. Published online January 19, 2022. doi:10.1056/NEJMoa2108330