FDA Approves Keytruda Plus Lenvima for Frontline RCC Treatment

The Food and Drug Administration (FDA) approved Keytruda (pembrolizumab) plus Lenvima (lenvatinib) for the frontline treatment of adult patients with advanced renal cell carcinoma (RCC).

“This approval is based in part on data demonstrating that Keytruda plus Lenvima significantly reduced the risk of disease progression or death versus sunitinib (Sutent),” said Dr. Robert Motzer, Jack and Dorothy Byrne Chair in Clinical Oncology, Kidney Cancer Section Head, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, in a statement. “This is a significant milestone for newly diagnosed patients with advanced renal cell carcinoma and introduces a promising combination option in the first-line setting.”

The approval was based off findings from the phase 3 CLEAR/KEYNOTE-581 trial, which involved 1,069 patients with advanced RCC who have not been previously treated. Participants were equally split up into three groups:

• 20 mg of Lenvima daily plus 200 mg of intravenous (IV) Keytruda every three weeks for up to 24 months
• 18 mg of oral Lenvima plus 5 mg of everolimus daily
• 50 mg of Sutent daily for four weeks on treatment, followed by four weeks off

Patients in the Keytruda/Lenvima arm had a 61% reduced risk of disease progression or death. Progression-free survival (PFS; the length of time a patient lives without their disease getting worse) was 23.9 months for those on the Keytruda/Lenvima arm, compared to only 9.3 months on the Sutent arm. Overall, the two-drug combination led to a 34% reduced risk of death compared to Sutent, with a 71% confirmed overall response rate (ORR; when patients disease shrinks due to treatment). ORR was 36% for those given Sutent.

“This FDA approval is truly significant for the advanced renal cell carcinoma community. The CLEAR/KEYNOTE-581 trial shows treatment with Keytruda plus Lenvima resulted in superior outcomes across progression-free survival, overall survival and objective response rate versus (Sutent) in patients with advanced renal cell carcinoma,” said Dr. Takashi Owa, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. “This milestone is a testament to our dedication to developing new therapeutic options for people living with advanced cancers, which is fueled by our passion for aiming to improve cancer care for patients, and amplified by the teamwork resulting from our collaboration with Merck.”

Since Keytruda works by activating the immune system to recognize and attack cancer cells, patients should be aware of immune-mediated side effects, which could be serious. They can include: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection and complications of allogeneic hematopoietic stem cell transplantation.

Lenvima can also come with serious side effects, such as hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, impaired wound healing, osteonecrosis of the jaw and embryo-fetal toxicity.

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