The combination of nivolumab (Opdivo) plus cabozantinib (Cabometyx) continued to show superior survival outcomes compared with single-agent sunitinib (Sutent) as first-line treatment for patients with advanced renal-cell carcinoma (RCC), according to extended follow-up data from the phase 3 CheckMate-9ER clinical trial presented at the 2021 ASCO Genitourinary Cancers Symposium.
With a minimum follow-up of 16 months, progression-free survival (PFS) and overall survival (OS) were almost twice as long for the combination versus sunitinib.
“The superior efficacy of nivolumab plus cabozantinib over sunitinib was maintained with extended 16-month minimum follow-up,” said lead investigator Robert J. Motzer, MD, Kidney Cancer Section Head, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY. “These results continue to support nivolumab plus cabozantinib as a potential new first-line treatment option for patients with advanced RCC.”
An exploratory subgroup analysis from the study suggested that survival and response benefits with this combination, as well as the safety profile, were valid, regardless of sarcomatoid histology.
Last year, data were presented for 641 patients from the randomized, controlled, phase 3 CheckMate-9ER trial, with a minimum follow-up of 10.6 months. At that time, the median PFS was 16.6 months with nivolumab plus cabozantinib versus 8.3 months with sunitinib, a 49% improvement favoring the combination therapy. The OS data were not yet reached in either arm of the study.
Based on the original data presented last year, in January 2021 the FDA approved the nivolumab plus cabozantinib combination as first-line treatment for patients with advanced RCC.
Longer Follow-Up
At the 2021 ASCO GU Cancers meeting, the median extended follow-up was 23.5 months. The median PFS in the intention-to-treat population was 17.0 months for nivolumab plus cabozantinib versus 8.3 months for sunitinib (P <.0001). The median OS was still not reached in the combination arm but was 29.5 months with sunitinib (P = .0034).
The objective response rate was significantly higher for nivolumab plus cabozantinib: 54.8% versus 28.4% for sunitinib. Complete response as best overall response was observed in 30 (9.3%) patients in the nivolumab plus cabozantinib arm versus 14 (4.3%) in the sunitinib monotherapy arm.
The median time to response was shorter for nivolumab plus cabozantinib: 2.8 months versus 4.2 months with sunitinib; the median duration of response was 21.7 months versus 12.7 months, respectively. At 18 months, the probability of ongoing response was 56% with nivolumab plus cabozantinib versus 43% with sunitinib.
Safety Profile
The adverse event profile for nivolumab plus cabozantinib was consistent with previous reports for each of the agents individually, and no new safety signals were observed. Grade 3 or 4 adverse events were 78.4% with the combination and 73.1% with sunitinib.
Discontinuation because of treatment-related adverse events was 9.7% for nivolumab, 7.2% for cabozantinib, and for both agents in 6.6% versus 9.1% for sunitinib.
Approximately 20% of those who received nivolumab plus cabozantinib required corticosteroids to manage immune-mediated adverse events.
Dr Motzer noted that these results were similar in the 75 patients included in the study who had sarcomatoid histology. No new safety signals were observed in the sarcomatoid subgroups.
“Notable efficacy benefits were observed with nivolumab plus cabozantinib versus sunitinib, regardless of sarcomatoid status,” Dr Motzer said.