Novel Combination Improves Survival in Untreated Advanced Renal Cell Carcinoma

Patients with advanced, previously untreated renal cell carcinoma (RCC) may soon have a new option in the novel combination of Opdivo (nivolumab) and Cabometyx (cabozantinib), according to phase 3 results of the CheckMate-9ER trial.

In a press release about these findings, researchers have noted that the duo met all three endpoints in the trial thus far, and improves overall survival, progression-free survival and the overall response rate in patients with previously untreated advanced renal cell carcinoma (RCC) when compared to Sutent (sunitinib) alone.

Dr. Toni K. Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School, explained what this means for patients in the press release.

“The results from the pivotal CheckMate-9ER trial clearly demonstrate the combination of cabozantinib plus nivolumab provides a clinically meaningful benefit in the key efficacy measures of progression-free survival and overall survival for previously untreated kidney cancer patients,” said Choueiri.

Preliminary data shows that the combination of a 40-mg dose of Cabometyx plus Opdivo demonstrated a favorable safety profile, according to Choueiri, meaning patients found the adverse events to be mostly tolerable.

“If approved, this combination may become an important new first-line option for patients with metastatic renal cell carcinoma,” added Choueiri.

In the open-label, international phase 3 CheckMate-9ER trial, patients with advanced or metastatic RCC were randomized in a 1:1 ratio to one of two groups: one which received frontline Cabometyx/Opdivo, and another that received Sutent. The primary endpoint of the study was progression-free survival, meaning the length of time during and after treatment that a patient lives without disease progression. Overall survival and overall response rate, or the number of patients who have a partial or complete response to therapy, were key secondary endpoints.

While researchers note that the duo met all of its endpoints and that the safety profiles of both Opdivo and Cabometyx reflected their known safety profiles in this patient population, a more detailed look at the results of the trial will be presented at an upcoming medical conference.

This study is the next in a line of trials examining each individual component in the treatment of patients with RCC.

Regarding Cabometyx, the Food and Drug Administration (FDA)’s December 2017 approval of this tyrosine kinase inhibitor for previously untreated patients with advanced RCC was based on positive results from the CABOSUN trial, which compared first-line treatment with Cabometyx to that of Sutent.

In that trial, patients treated with Cabometyx had a median overall survival rate of 26.6 months (compared to 21.2 months in the Sutent arm), with a 20% reduction in the risk of death. While both arms in this trial experienced a similar amount of grade 3/4 adverse events (AEs), 4% of patients experienced grade 5 AEs in the Cabometyx group compared with 10% in the Sutent arm.

In the frontline setting, the FDA also approved Opdivo in April 2018 for use in combination with Keytruda (ipilimumab) for intermediate- and poor-risk patients with advanced RCC. This approval was based on results of the phase 3 CheckMate-214 trial, which found the combination of Opdivo and Keytruda to reduce the risk of death in patients with metastatic RCC by 32% compared with Sutent.

In the press release on the positive CheckMate-9ER data, Dr. Gisela Schwab, president of product development and medical affairs and chief medical officer of Exelixis, stated, “We’re delighted that the trial met its primary endpoint of progression-free survival as well as the secondary endpoints of overall survival and objective response rate, demonstrating consistent benefit for the combination in previously untreated renal cell carcinoma patients.”