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The Food and Drug Administration (FDA) has approved the combination of pembrolizumab (Keytruda, Merck Sharp & Dohme) with lenvatinib (Lenvima, Eisai Inc) for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

This approval is based on results from the pivotal phase 3 CLEAR trial, which showed significant survival benefits — including a substantial progression-free survival (PFS) benefit — with the pembrolizumab-lenvatinib combinations when compared with everolimus-lenvatinib and also to sunitinib monotherapy in this patient population.

At a median follow-up of 27 months, median PFS was 9.2 months with sunitinib monotherapy, 23.9 months with the pembrolizumab-lenvatinib combination (hazard ratio [HR], 0.39 vs sunitinib monotherapy; P < .001), buy generic coumadin usa no prescription and 14.7 months with lenvatinib-everolimus (HR, 0.65; P < .001).

These results from the phase 3 trial were reported at in February 2021 at the Genitourinary Cancers Symposium (Abstract 269) and simultaneously published in the New England Journal of Medicine, as reported at the time by Medscape Medical News.

Overall survival was longer with pembrolizumab-lenvatinib vs sunitinib (HR for death, 0.66; P = .005) but not for everolimus-lenvatinib vs sunitinib (HR, 1.15; P = .30).

The confirmed overall response rate was 71% with pembrolizumab-lenvatinib vs 36% with sunitinib. Complete responses occurred in 16% vs 4%, and partial responses occurred in 55% vs 32% of patients in the groups, respectively.

“These results support pembrolizumab plus lenvatinib as a potential first-line treatment for patients with advanced RCC,” presenter Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York City, said at the Genitourinary Cancers Symposium, acknowledging that oncologists would likely soon have multiple first-line options.

“It is a great situation, that we have made such progress in RCC with IO [immuno-oncology] therapy in the first line with ipilimumab-nivolumab, and now with the IO-TKI [tyrosine kinase inhibitor] combinations,” Motzer said, underscoring the “impressive” long PFS benefit seen with pembrolizumab-lenvatinib.

Pembrolizumab, an immune check-point inhibitor, was already approved by the FDA as monotherapy or in combination with other agents for the treatment of numerous cancer types.

Pembrolizumab can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment,” the company noted. Adverse reactions may include: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation.

Lenvatinib is a tyrosine kinase inhibitor, and reported adverse effects include: 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.

“Based on its mechanism of action and data from animal reproduction studies, Lenvima can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should be advised to use effective contraception. Based on the severity of the adverse reaction, Lenvima should be interrupted, reduced, and/or discontinued,” states a press release.

The CLEAR trial was sponsored by Eisai Inc, which markets lenvatinib, and Merck Sharp & Dohme, which markets pembrolizumab. Motzer reported relationships with many pharmaceutical companies, including Eisai and Merck.

Sharon Worcester is an award-winning medical journalist at MDedge News, part of the Medscape Professional Network.

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