First-line nivolumab plus cabozantinib superior to sunitinib in advanced renal cell carcinoma

First-line treatment of advanced renal cell carcinoma (aRCC) with nivolumab plus cabozantinib (N+C) results in sustained survival and response benefits at 3 years minimum follow-up, which is consistent with previous follow-ups, according to a study presented at the 2023 ASCO GU Cancers Symposium.

Compared with the previous data cut, median overall survival (OS) with N+C has improved by 11.8 months. Responses are also durable with N+C, showing higher complete response rates relative to sunitinib, irrespective of the International Metastatic RCC Database Consortium risk group.

“First-line N+C demonstrated superiority over sunitinib with 25.4 months minimum follow-up (median, 32.9 months) in patients with aRCC in the CheckMate 9ER trial,” said the researchers, led by Mauricio Burotto from Bradford Hill Clinical Research Center, Santiago, Chile.

“Here, we report survival, response per blinded independent central review (BICR), and safety after 3 years minimum follow-up in all randomized patients and by IMDC risk score,” they added.

Burotto and his team randomly assigned patients 1:1 (stratified by IMDC risk score, tumor PD-L1 expression, region) to receive nivolumab 240 mg flat dose IV Q2W plus cabozantinib 40 mg PO QD or sunitinib 50 mg PO for 4 weeks (6-week cycles) until disease progression or unacceptable toxicity (max nivolumab treatment, 2 years).

Progression-free survival (PFS) by BICR was the primary endpoint, while secondary ones included OS, objective response rate (ORR) by BICR, and safety.

Overall, 323 patients were treated with N+C and 328 with sunitinib. In intent-to-treat patients, N+C demonstrated consistent PFS and OS benefits compared with sunitinib with 36.5 months minimum follow-up. [ASCO GU 2023, abstract 603]

Specifically, median PFS of N+C relative to sunitinib was 16.6 vs 8.4 months (hazard ratio [HR], 0.58, 95 percent confidence interval [CI], 0.48‒0.71; p<0.0001), while median OS was 49.5 vs 35.5 months (HR, 0.70, 95 percent CI, 0.56‒0.87; p=0.0014).

ORR was also higher with N+C compared with sunitinib (56 percent vs 28 percent), as was the number of patients achieving complete response (12 percent vs 5 percent). The median duration of response was 23.1 months for N+C and 15.2 months for sunitinib.

Treatment-related adverse events (TRAE) of any grade occurred at comparable rates between the N+C and sunitinib arms (97 percent vs 93 percent; grade ≥3 TRAE, 67 percent vs 55 percent). Notably, TRAEs led to the discontinuation of cabozantinib in 10 percent of patients, nivolumab in 10 percent, both agents in 7 percent, or either agent in 28 percent, and sunitinib in 11 percent.

“No new safety signals emerged with additional follow-up in either arm,” according to the researchers. “These results continue to support N+C as a first-line treatment for patients with aRCC.”

In the CheckMate 9ER trial, Burotto and colleagues reported improved efficacy with N+C vs sunitinib, supporting the combination in the first-line treatment of aRCC. [Lancet Oncol 2022;23:888-898]

CheckMate 9ER is an open-label, randomized, phase III trial conducted in 125 hospitals and cancer centres across 18 countries, which assessed patients with previously untreated metastatic or aRCC.