by Dr. C.H. Weaver M.D. updated 9/2019
Doctors from Memorial Sloan Kettering Cancer Center in New York report that the combination of Lenvima (lenvatinib) plus Keytruda (pembrolizumab) may represent a new treatment option for patients with advanced uterine (endometrial) cancer. (1)
Lenvima is a multikinase receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3. Lenvima™ also inhibits other RTKs that have been implicated in cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4 and the platelet derived growth factor receptor alpha (PDGFR), KIT, and RET. Learn more about Lenvima
About Keytruda Checkpoint Inhibitors
Keytruda belongs to a class of medicines called “checkpoint inhibitors.” Checkpoint inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the colon cancer cells.
Between September 10, 2015, and July 24, 2017 doctors enrolled 54 patients with metastatic endometrial cancer at 11 centers across the United States to receive treatment with Lenvima 20 mg daily plus Keytruda 200 mg every 3 weeks. Overall 40% of patients responded to treatment when assessed 24 weeks after beginning therapy.
The United States Food and Drug Administration (FDA) granted accelerated approval to the combination of Keytruda and Lenvima for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and are not candidates for curative surgery or radiation based on this and additional information. (2,3)
The 111/KEYNOTE-146 single-arm clinical trial was the basis for the FDA approval. The study evaluated 108 women with metastatic endometrial carcinoma that had progressed following at least one prior systemic therapy. All patients were treated with the Keytruda + Lenvima combination every 3 weeks until they experienced disease progression or unacceptable side effects.
Among the 108 patients, 94 had tumors that were not MSI-H or dMMR, 11 had tumors that were MSI-H or dMMR, and in 3 patients the tumor MSI-H or dMMR status was not known. Tumor MSI status was determined using a polymerase chain reaction test and MMR status was determined using an immunohistochemistry test.
The overall response rate in patients whose tumors were not MSI-H or dMMR was 38.3% with 10 complete responses (10.6%) and 26 partial responses (27.7%). The average duration of response in these advanced patients has not been reached at the time of analyses 69% of those responding to treatment have response durations greater than 6 months.
Treatment was well tolerated however patients did report some side effects. Fatigue, diarrhea, and hypothyroidism were the most common.
The combination of Keytruda and Lenvima appears to provide benefit to women with advanced uterine cancer that are not MSI-H or dMMR. Patients with uterine cancer should discuss the role of genomic testing and tumor profiling with their doctors as these tests can help determine whether newer precision cancer medicines like Keytruda and Lenvima will play a role in the management of their cancer.
- Lancet Oncol. 2019 Mar 25. Epub ahead of print.
- FDA takes first action under new international collaboration with Australia and Canada designed to provide a framework for concurrent review of cancer therapies, approving treatment for patients with endometrial carcinoma. FDA website. Posted September 17, 2019. <a href="https://bit.ly/2kqmAGq.">https://bit.ly/2kqmAGq.</a> Accessed September 17, 2019.
- Makker V, Rasco D, Vogelzang NJ, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20(5):711-718. doi: 10.1016/S1470-2045(19)30020-8