FDA Approves Endometrial Cancer Treatment Under New International Network Pathway

The U.S. Food and Drug Administration (FDA) granted accelerated approval to Lenvima® (lenvatinib) plus Keytruda® (pembrolizumab) for the treatment advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) in patients whose disease has progressed following prior systemic therapy but are not candidates for curative surgery or radiation.

The FDA, along with the Australian Therapeutic Goods Administration and Health Canada, approved this combination through Project Oribis, a new international framework for concurrent submission and review of oncology drugs. Project Orbis only applies to supplemental oncology approvals or approvals for new indications of previously approved therapies, not new drug applications.

Response observed with lenvatinib and pembrolizumab

The recent approval was based on results of a study that included 94 patients with endometrial carcinoma tumors that were not MSI-H or dMMR. Ten patients (10.6% of responders) had a complete response and 26 (27.7% of responders) had a partial response. The objective response rate was 38.3%. Twenty-five of these patients (69% of responders) had a response duration of more than six months.

Common adverse events (AEs) associated with this combination include fatigue, high blood pressure, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea, and stomatitis. Other AEs include vomiting, decreased weight, abdominal pain, headache, constipation, urinary tract infection, dysphonia, hemorrhagic events, hypomagnesemia, palmar-plantar erythrodysesthesia, dyspnea, cough, and rash.

Women who are pregnant or breastfeeding should not take this combination.