FDA Approves Nivolumab in Combination With Cabozantinib As First-Line Treatment for Advanced Renal Cell Carinoma

The approval is for a 240 mg injection of nivolumab every 2 weeks or 480 mg every 4 weeks in combination with 40 mg once daily of cabozantinib.

Nivolumab (Opdivo, Bristol Myers Squibb) has been approved by the FDA in combination with cabozantinib (Cabometyx, Exelixis) for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

The approved indication is for a 240 mg injection of nivolumab every 2 weeks or 480 mg every 4 weeks in combination with 40 mg once daily of cabozantinib. The approval is based on the phase 3 CheckMate -9ER trial, which compared nivolumab and cabozantinib with sunitinib in patients with advanced RCC.

“The role of Opdivo [and] Yervoy is well established for intermediate/poor-risk patients with advanced RCC, and today’s achievement extends the potential of an Opdivo-based combination to even more patients,” said Adam Lenkowsky, general manager and head of US Oncology, Immunology, and Cardiovascular at Bristol Myers Squibb, in a press release. “Opdivo in combination with Cabometyx brings together the strong heritage of both medicines to now provide a new combination in advanced RCC that may offer improved outcomes to patients for whom an immunotherapy plus tyrosine kinase inhibitor regimen is appropriate.”

The primary endpoint of the CheckMate -9ER trial was progression-free survival (PFS) and the secondary endpoints included overall survival and objective response rate (ORR). According to the press release, patients treated with nivolumab in combination with cabozantinib lived twice as long without tumor progression compared to patients who were treated with sunitinib. The median PFS was 16.6 months and 8.3 months, respectively. The combination therapy also reduced the risk of death by 40% compared to sunitinib.

Further, more patients responded to the combination than sunitinib, with an ORR of 55.7% compared to 27.1%. In the combination arm, 8% of patients experienced a complete response and 47.7% experienced a partial response, compared to 4.6% and 22.6%, respectively, in the sunitinib arm. Among patients who responded, the median duration of response was 20.2% months in the combination arm and 11.5 months in the sunitinib arm.

“This combination of cabozantinib and nivolumab significantly improved key efficacy measures compared to sunitinib—progression-free survival, overall survival, and objective response rate—while showing a low rate of treatment discontinuations due to side effects,” said Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, in a statement. “The therapeutic benefit demonstrated in CheckMate -9ER and quality of life measures explored emphasize the role of this combination for patients with advanced kidney cancer. With this important FDA approval, the combination is poised to become a standard in newly diagnosed metastatic kidney cancer.”

Adverse reactions greater than grade 3 were similar with the combination treatment compared to sunitinib. All-cause adverse reactions leading to discontinuation of either nivolumab or cabozantinib occurred in 19.7% of patients, with 6.6% discontinuing just nivolumab, 7.5% discontinuing just cabozantinib, and 5.6% discontinuing the combination.

“While significant progress has been made in the treatment landscape for advanced kidney cancer over the last several years, patients still need more therapeutic options to treat this disease as we search for a possible cure,” said Bryan Lewis, JD, president and co-founder of KidneyCAN, in a press release. “As patients are living longer with advanced kidney cancer, focusing on the safety and effectiveness of new treatments has become even more important. The findings for the combination of Opdivo and Cabometyx in the CheckMate -9ER trial make the FDA approval of this combination a notable development for the patient community.”

REFERENCE

US Food and Drug Administration Approves Opdivo (nivolumab) in Combination With Cabometyx (cabozantinib) as First-Line Treatment for Patients with Advanced Renal Cell Carcinoma [news release]. Bristol Myers Squibb; January 22, 2021. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-OPDIVO-nivolumab-in-Combination-with-CABOMETYX-cabozantinib-as-First-line-Treatment-for-Patients-with-Advanced-Renal-Cell-Carcinoma/default.aspx. Accessed January 22, 2021.