The Food and Drug Administration (FDA) has granted regular approval to Keytruda® (pembrolizumab) in combination with Lenvima® (lenvatinib) for patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. This indication had previously been granted accelerated approval based on data from the phase 1b/2 KEYNOTE-146 trial (ClinicalTrials.gov Identifier: NCT02501096).
The full approval was based on data from the multicenter, open-label, randomized, active-controlled confirmatory phase 3 KEYNOTE-775 trial (ClinicalTrials.gov Identifier: NCT03517449), which assessed the efficacy and safety of pembrolizumab in 827 adults with advanced endometrial carcinoma previously treated with at least 1 prior platinum-based chemotherapy regimen, including neoadjuvant and adjuvant settings. Patients were randomly assigned 1:1 to receive either pembrolizumab 200mg intravenously every 3 weeks with lenvatinib 20mg orally once daily or an investigator’s choice of chemotherapy, consisting of doxorubicin or paclitaxel.
The coprimary endpoints were progression free survival (PFS) and overall survival (OS). Key secondary endpoints included objective response rate (ORR) and duration of response (DOR).
Findings showed that median PFS was 6.6 months (95% CI, 5.6-7.4) for the pembrolizumab plus lenvatinib arm compared with 3.8 months (95% CI, 3.6-5.0) for the chemotherapy arm (hazard ratio [HR] 0.60; 95% CI, 0.50-0.72; P <.0001). Median OS was 17.4 months (95% CI, 14.2-19.9) for the pembrolizumab plus lenvatinib arm compared with 12 months (95% CI, 10.8-13.3) for the chemotherapy arm (HR 0.68; 95% CI, 0.56-0.84; P =.0001).
The ORR was 30% (95% CI, 26-36) for the pembrolizumab plus lenvatinib arm and 15% (95% CI, 12-19) for the chemotherapy arm (P <.0001). Median DOR was 9.2 months (1.6+, 23.7+) for pembrolizumab plus lenvatinib and 5.7 months (0.0+, 24.2+) for chemotherapy.
The most common adverse reactions reported with pembrolizumab plus lenvatinib were hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight loss, abdominal pain, urinary tract infection, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia and rash.
“With a 5-year survival rate of just 17%, women with advanced endometrial cancer who are not candidates for curative therapy, particularly those with disease progression following prior systemic therapy, have limited treatment options,” said Dr Vicky Makker, principal investigator and medical oncologist, Memorial Sloan Kettering Cancer Center. “This approval is an important step forward in helping patients fight this difficult-to-treat malignancy, as physicians can now provide an option that may improve survival outcomes.”
- FDA grants regular approval to pembrolizumab and lenvatinib for advanced endometrial carcinoma. News release. US Food and Drug Administration. Accessed July 22, 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-regular-approval-pembrolizumab-and-lenvatinib-advanced-endometrial-carcinoma.
- FDA approves Keytruda® (pembrolizumab) plus Lenvima® (lenvatinib) combination for patients with certain types of advanced endometrial carcinoma. News release. Merck and Eisai Inc. Accessed July 22, 2021. https://www.businesswire.com/news/home/20210722005478/en/FDA-Approves-KEYTRUDA%C2%AE-pembrolizumab-Plus-LENVIMA%C2%AE-lenvatinib-Combination-for-Patients-With-Certain-Types-of-Advanced-Endometrial-Carcinoma.
- Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2021.
- Lenvima [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2021.