The FDA has approved lenvatinib (Lenvima®, Eisai) plus pembrolizumab (Keytruda®, Merck) for patients with advanced endometrial carcinoma who experience disease progression after at least one prior systemic therapy but are ineligible for curative surgery or radiation. Lenvatinib/pembrolizumab is indicated for patients whose cancer is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).
"Lenvatinib is a multikinase inhibitor of VEGFR1, VEGFR2, and VEGFR3, and other receptor tyrosine kinases," write Vicky Makker, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, and colleagues in their phase 2 study evaluating the efficacy of lenvatinib/pembrolizumab. "Pembrolizumab, an antibody targeting PD-1, has moderate efficacy in biomarker-unselected endometrial cancer."
The approval was based on Keynote-146 (NCT02501096), a single-arm, multicenter, open-label, multi-cohort trial that enrolled 94 patients with metastatic endometrial carcinoma who experienced disease progression after one or more previous lines of systemic therapy and whose tumors were not MSI-H or dMMR. Patients received 20 mg of lenvatinib orally twice a day in addition to an intravenous infusion of 200 mg of pembrolizumab every three weeks until disease progression or unacceptable toxicity. The study's primary end points were objective response rate and duration of response, determined by independent radiologic review using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Lenvatinib/pembrolizumab achieved an overall response rate of 38.3%, including 10 complete responses (10.6%) and 26 partial responses (27.7%). Response durations of at least six months were experienced by 25 patients (69%).
Adverse events experienced by at least 20% of patients included fatigue, hypertension, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea, stomatitis, vomiting, decreased weight, abdominal pain, headache, constipation, urinary tract infection, dysphonia, hemorrhagic events, hypomagnesemia, palmar-plantar erythrodysesthesia, dyspnea, cough, and rash.
The recommended dosage of lenvatinib/pembrolizumab for patients with advanced endometrial carcinoma is 20 mg of lenvatinib orally once daily and 200 mg of pembrolizumab administered intravenously once every three weeks.
For More Information
Clinicaltrials.gov (2019). Lenvatinib in combination with pembrolizumab versus treatment of physician's choice in participants with advanced endometrial cancer (MK-3475-775/E7080-G000-309 per Merck Standard Convention [KEYNOTE-775]). NLM identifier: NCT03517449.
Makker V, Herraez AC, Aghajanian C, et al (2019). A phase 3 trial evaluating efficacy and safety of lenvatinib in combination with pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol. [Epub ahead of print] DOI:10.1200/JCO.2019.37.15_suppl.TPS5607
Makker V, Rasco D, Vogelzang NJ, et al (2019). Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicenter, open-label, single-arm, phase 2 trial. Lancet Oncol, 20(5):711-718. DOI:10.1016/S1470-2045(19)30020-8
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