The Food and Drug Administration (FDA) has approved Keytruda® (pembrolizumab) in combination with Lenvima® (lenvatinib) for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

The approval was based on data from the multicenter, open-label, randomized phase 3 CLEAR (Study 307)/KEYNOTE-581 trial ( Identifier: NCT02811861) that evaluated the efficacy and safety of pembrolizumab plus lenvatinib as first-line treatment in 1069 adults with advanced RCC. Patients were ineligible if they had active autoimmune disease or a medical condition that required immunosuppression.

Patients were randomly assigned 1:1:1 to receive pembrolizumab 200mg intravenously (IV) every 3 weeks plus lenvatinib 20mg orally once daily for up to 24 months, or lenvatinib 18mg orally once daily plus everolimus 5mg orally once daily, or sunitinib 50mg orally once daily for 4 weeks on treatment followed by 2 weeks off. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and confirmed objective response rate (ORR).

Findings showed that the median PFS was 23.9 months (95% CI, 20.8-27.7) for the pembrolizumab plus lenvatinib arm compared with 9.2 months (95% CI, 6.0-11.0) for the sunitinib arm (hazard ratio [HR] 0.39; 95% CI, 0.32-0.49; P <.0001). For OS, the pembrolizumab plus lenvatinib arm showed a 34% reduction in the risk of death compared with sunitinib (HR 0.66; 95% CI, 0.49-0.88; P =.0049).

The confirmed ORR was 71% (95% CI, 66-76) (n=252) for the pembrolizumab plus lenvatinib arm compared with 36% (95% CI, 31-41) (n=129) for the sunitinib arm (P <.0001). Among responders, a complete response was observed in 16% of the pembrolizumab plus lenvatinib arm and 4% of the sunitinib arm.

The most common adverse reactions with pembrolizumab plus lenvatinib include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight loss, abdominal pain, urinary tract infection, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia, rash, hepatotoxicity, and acute kidney injury.

“In the study, Keytruda plus Lenvima demonstrated a survival benefit for patients with advanced renal cell carcinoma, supporting the importance of this combination as a new first-line treatment option for these patients,” said Dr Gregory Lubiniecki, Vice President, Oncology Clinical Research, Merck Research Laboratories.


  1. FDA approves Keytruda® (pembrolizumab) plus Lenvima® (lenvatinib) combination for first-line treatment of adult patients with advanced renal cell carcinoma (RCC). News release. Merck & Co., Inc. Accessed August 12, 2021.
  2. Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2021.