The Food and Drug Administration (FDA) has approved the combination of pembrolizumab (Keytruda; Merck), a human programmed death receptor-1 (PD-1)-blocking antibody, and lenvatinib (Lenvima; Eisai), a kinase inhibitor, for the treatment of 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. 

The approval was based on data from a single-arm, open-label trial in patients with endometrial carcinoma whose tumors had progressed following one line of systemic therapy and were not MSI-H or dMMR (n=94). Patients were treated with pembrolizumab 200mg intravenously every 3 weeks plus lenvatinib 20mg orally once daily until unacceptable toxicity or disease progression. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR).

Results showed an ORR of 38.3% (95% CI, 29% to 49%), with a complete response rate of 10.6% (n=10) and a partial response rate of 27.7% (n=26). The median follow-up time was 18.7 months. Among the 36 patients who had a response, the median DoR was not reached (range: 1.2+ to 33.1+ months); 69% of these patients experienced responses lasting ≥6 months.

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With regard to safety, the most common adverse reactions (≥20%) reported were fatigue, musculoskeletal pain, hypertension, diarrhea, decreased appetite, hypothyroidism, nausea, stomatitis, vomiting, decreased weight, abdominal pain, headache, constipation, urinary tract infection, dysphonia, hemorrhagic events, hypomagnesemia, palmar-plantar erythrodysesthesia syndrome, dyspnea, cough, and rash. Fatal adverse reactions occurred in 3% of patients; these included gastrointestinal perforation, reversible posterior leukoencephalopathy syndrome (RPLS) with intraventricular hemorrhage, and intracranial hemorrhage.


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“Based on objective response rate and the duration of response, this approval of the [pembrolizumab] plus [lenvatinib] combination will help address a significant unmet medical need for patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation,” said Dr Vicky Makker, medical oncologist, Memorial Sloan Kettering Cancer Center.

For more information visit merck.com or eisai.com.