Lenvatinib Plus Pembrolizumab Combo Prolongs PFS in Advanced Endometrial Cancer


The KEYNOTE-775 trial found that lenvatinib plus pembrolizumab prolonged progression-free survival compared with chemotherapy for patients with endometrial cancer.

The combination of lenvatinib (Lenvima) plus pembrolizumab (Keytruda) yielded a longer progression-free survival (PFS) vs chemotherapy for patients with advanced endometrial cancer, according to results from the phase 3 KEYNOTE-775 trial (NCT03517449) published in the New England Journal of Medicine.

The median PFS was 6.6 months in the combination group vs 3.8 months in the chemotherapy group among patients who were mismatch repair–proficient (pMMR; HR, 0.60; 95% CI, 0.50-0.72; P <.001). The median PFS in the overall population was 7.2 months in the combination group and 3.8 months in the chemotherapy group (HR, 0.56; 95% CI, 0.47-0.66; P <.001). The median overall survival (OS) in the pMMR population was 17.4 months in the combination group and 12.0 months in the chemotherapy group (HR, 0.68; 95% CI, 0.56-0.84; P <.001). For the overall population, the median OS was 18.3 months vs 11.4 months (HR, 0.62; 95% CI, 0.51-0.75; P <.001) in the combination and chemotherapy groups, respectively.

A total of 827 patients enrolled on the trial, 697 of whom were pMMR and 130 were mismatch repair–deficient (dMMR). Patients received either 20 mg of lenvatinib orally once daily plus 200 mg of pembrolizumab intravenously every 3 weeks or physicians choice chemotherapy. Median follow-up was 12.2 months in the lenvatinib group and 10.7 months in the chemotherapy group.

Objective response was confirmed in 30.3% of patients in the combination group and 15.1% in the chemotherapy group, in the pMMR population. The overall population had an objective response of 31.9% in the combination group and 14.7% in the chemotherapy group. The complete response rate in the pMMR population was 5.2% among those in receiving combination therapy and 2.6% for those receiving chemotherapy, with the overall population experiencing a rate of 6.6% and 2.6%, respectively.

The median duration of response (DOR) in the pMMR population was 9.2 months in the combination group and 5.7 months in the chemotherapy group, with the overall population experiencing a median DOR of 14.4 months and 5.7 months, respectively.

Patients in the combination group experienced tumor shrinkage and improvement in efficacy across all end points compared with the chemotherapy group.

Grade 3 or higher adverse effects (AEs) occurred in 88.9% of patients receiving combination therapy and 72.7% receiving chemotherapy. Common serious AEs included hypertension in 4.2% of patients in the lenvatinib group and neutropenia in 4.1% of those in the chemotherapy group. Additionally, 5.7% of patients in the combination arm experience grade 5 AEs vs 4.9% in the chemotherapy arm.

In the combination group, 66.5% of patients had AEs that led to dose reduction, 69.2% led to dose interruptions, and 33.0% led to discontinuation. In the chemotherapy arm, 12.9% had dose reductions from AEs and 27.1% discontinued. AEs of interest were observed in 67.2% of patients taking pembrolizumab and included hyperthyroidism with incidence of 57.6% among patients receiving combination therapy.

In the intent-to treat population, 28.0% of patients in the combination group and 48.1% in the chemotherapy group received subsequent anticancer medication. Additionally, 9.1% in the chemotherapy group who were pMMR received the combination therapy as subsequent treatment and 16.9% of those who were dMMR received PD-1 pathway targeting monotherapy or combination regimens.


Makker V, Colombo N, Casado Herráez A, et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. 2022;386(5):437-448. doi:10.1056/NEJMoa2108330

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