The long-term efficacy benefit of the nivolumab and cabozantinib combination vs sunitinib as a frontline treatment for advanced renal cell carcinoma (aRCC) is observed through the final results of the CheckMate 9ER trial, with the report covering a minimum follow-up of 5 years first presented at ASCO GU 2025.

Both the progression-free survival (PFS) and overall survival (OS) benefits, as well as the higher objective response rate (ORR), were retained after an additional 4 years of follow-up since the primary analysis, continuing to favour the immuno-oncology (IO)-TKI doublet over sunitinib. [ASCO GU 2025, abstract 439]

“These results continue to support nivolumab plus cabozantinib as a standard of care for previously untreated aRCC,” said Dr Robert Motzer from the Memorial Sloan Kettering Cancer Center, New York City, New York, US.

Survival benefits

The median PFS, as assessed by blinded independent central review (BICR), was 16.4 months in patients treated with IV nivolumab plus cabozantinib vs 8.3 months in those treated with sunitinib using the 4/2 schedule (hazard ratio [HR], 0.58, 95 percent confidence interval [CI], 0.49?0.70).

Compared with the last report, the difference in the median OS widened slightly to 11 months: 46.5 months in the nivolumab plus cabozantinib arm vs 35.5 months in the sunitinib arm (HR, 0.79, 95 percent CI, 0.65?0.96). [ASCO GU 2024, abstract 362]

The OS rates at years 4 and 5 were 48.9 percent vs 39.4 percent and 40.9 percent vs 35.4 percent, respectively.

“There remains separation of the curves,” said Motzer. “The long-term follow-up highlights that nearly 50 percent of patients were alive at 4 years, and 41 percent at 5 years following treatment with nivolumab plus cabozantinib.”

The median OS attained by patients treated with the IO-TKI doublet was particularly long among those with International Metastatic RCC Database Consortium favourable risk (53.7 months), while an OS benefit vs sunitinib can be established in patients with intermediate or poor risk (median 43.9 vs 29.2 months; HR, 0.74, 95 percent CI, 0.60?0.92).

“The abstract presenting the final update of CheckMate 9ER showed that patients with metastatic disease are living longer, and the median survival is now up to about 4 years,” said discussant Dr Tian Zhang from the UT Southwestern Medical Center, Dallas, Texas, US. “There is no doubt that immunotherapy doublets have extended OS for patients in the frontline setting.”

Median follow-up of 5.6 years

The final confirmed ORR was 55.7 percent with nivolumab plus cabozantinib vs 27.4 percent with sunitinib. Only 6.5 percent of patients treated with nivolumab plus cabozantinib had progressive disease as their best objective response, which makes it “one of the highlights of this IO-TKI regimen”, as Motzer described, vs 14.3 percent of patients treated with sunitinib.

The current analysis (n=651) was conducted at a median follow-up for OS of 67.6 months and represented a 12-month extension in follow-up from the last report.

The trio of efficacy endpoints ? PFS per BICR, OS, and ORR per BICR ? had already been met in a hierarchical order since the primary report (median follow-up 18.1 months). [N Engl J Med 2021;384:829-841] Since the difference in OS was tested as significant using the α spent at that early analysis, further formal analysis of survival was not required, and all efficacy results were reported descriptively at longer follow-ups. [Lancet Oncol 2022;23:888-898]