FDA Approves Frontline Pembrolizumab and Lenvatinib Combination for Advanced RCC

The FDA has granted approval to the combination of pembrolizumab (Keytruda) and lenvatinib (Lenvima) for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC), according to a press release issued by Merck and Eisai.

The approval is supported by findings from the phase 3 CLEAR trial, in which the pembrolizumab/lenvatinib reduced the risk of disease progression or death by 61% (HR, 0.39; 95% CI, 0.32-0.49]; P <.0001) compared with sunitinib (Sutent). The median progression-free survival (PFS) observed with the combination was 23.9 months versus 9.2 months for sunitinib.

During a prior interview with Targeted Oncology^TM about the CLEAR study results, Robert Motzer, MD, Jack and Dorothy Byrne Chair in Clinical Oncology, Kidney Cancer Section Head, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, stated "said I think the standout from the trial was the efficacy gain for lenvatinib plus pembrolizumab. I think that the results of that were extremely impressive. And I think that's a good choice for first-line treatment for RCC."

Motzer added, in a press release, “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 combination of pembrolizumab and lenvatinib also reduced the risk of death by 34% (HR, 0.66; 95% CI: 0.49-0.88]; P =0.0049) in the study compared with sunitinib. confirmed objective responses were observed in 71% (95% CI: 66-76) of the combination arm versus 36% (95% CI: 31-41)of the sunitinib arm.

The confirmed ORR for the experimental combination was 71% compared to 36% in the control group. In the experimental group, 16% of patients experienced a complete response (CR) and 55% experienced a partial response (PR). In the control group, 4% experienced a CR and 32% experienced a PR.

Fatal AEs occurred in 4.3% of patients who received the combination. Serious AEs occurred in 51% of patents. Serious AEs included hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal insuciency (2%), dyspnea (2%), and pneumonia (2%). Thirty-seven percent of patients in the pembrolizumab/lenvatinib arm discontinued treatment. Dose interruption occurred in 78% of patients.

The most common all-grade AEs for the combination included fatigue (63%), diarrhea (62%), musculoskeletal disorders (58%), hypothyroidism (57%), hypertension (56%), and stomatitis (43%). 

“This FDA approval reinforces the potential of Keytruda plus Lenvima, which is now approved for two different types of cancer. 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, in the press release.

_Reference:

_{FDA Approves Keytruda® (pembrolizumab) plus Lenvima® (lenvatinib) combination for first-linetreatment of adult patients with advanced renal cell carcinoma (RCC). News release. Merck and Eisai. August 11, 2021. Accessed August 11, 2021.}