NICE Endorses Cabozantinib Plus Nivolumab in Advanced RCC


NICE has recommended the combination of cabozantinib and nivolumab for adult patients with advanced renal cell carcinoma in a final draft guidance.

John McGrane, MD

John McGrane, MD

The English National Institute for Health and Care Excellence (NICE) has recommended cabozantinib (Cabometyx) with nivolumab (Opdivo) for the treatment of adult patients with advanced renal cell carcinoma (RCC).1

NICE clarified that the recommendation is only for patients with intermediate- or poor-risk disease for whom nivolumab with ipilimumab (Yervoy) or lenvatinib (Lenvima) with pembrolizumab (Keytruda) would otherwise be offered. The agency also noted that the recommendation is not intended to affect treatment with cabozantinib with nivolumab that was initiated before its publication.

The recommendation is supported by findings from the phase 3 CheckMate 9ER trial (NCT03141177), which compared nivolumab plus cabozantinib with sunitinib (Sutent) in patients with previously untreated advanced RCC. Findings from the 55-month follow-up of the study presented during the 2024 Genitourinary Cancers Symposium demonstrated that patients who received the combination (n = 323) achieved a median progression-free survival (PFS) of 16.4 months (95% CI, 12.5-19.3) compared with 8.4 months (95% CI, 7.0-9.7) among those who received sunitinib (n = 328; HR, 0.58; 95% CI, 0.49-0.70). Additionally, at a median follow-up of 55.6 months (range, 48.1-68.1), the median OS was 46.5 months (95% CI, 40.6-53.4) vs 36.0 (95% CI, 29.2-42.8), respectively (HR, 0.77; 95% CI, 0.63-0.95).2

“The availability of cabozantinib in combination with nivolumab represents a step-change in the management of advanced kidney cancer and a valuable addition to the treatment options available,” John McGrane, MD, a consultant oncologist at Royal Cornwall Hospitals NHS Trust, in Truro, England, said in a press release. “Access to this treatment combination could provide valuable additional time for people living with advanced RCC in England and Wales.”3

CheckMate 9ER enrolled patients with previously untreated advanced RCC of any clear cell component and any International Metastatic RCC Database Consortium (IMDC) risk group. Eligible patients were randomly assigned 1:1 to receive nivolumab 240 mg every 2 weeks plus cabozantinib 40 mg daily or sunitinib 50 mg daily for 4 weeks on and 2 weeks off. Patients were stratified by IMDC risk score, PD-L1 expression, and geographic region.2

The primary end point was PFS by blinded independent central review per RECIST v1.1 criteria. Secondary end points included OS, overall response rate (ORR), and safety. Health-related quality of life was assessed as an exploratory end point.

Notably, patients with IMDC intermediate- or poor-risk disease experienced a significant benefit with nivolumab plus cabozantinib (n = 249) compared with sunitinib (n = 256), with a median PFS of 15.4 months (95% CI, 11.1-18.6) vs 7.1 (95% CI, 5.7-8.9), respectively (HR, 0.56; 95% CI, 0.45-0.68). Moreover, the median OS in this population was 43.9 months (95% CI, 34.9-51.9) vs 29.3 months (95% CI, 23.7-36.2), respectively (HR, 0.73; 95% CI, 0.58-0.91).

In the safety population, patients in the combination arm (n = 320) experienced any-grade treatment-related adverse effects (TRAEs) at a rate of 98% compared with 93% in the control arm (n = 320). The most common any-grade TRAEs in the combination arm were diarrhea (59%), palmar-plantar erythrodysesthesia (39%), and hypertension (34%). These TRAEs occurred at respective rates of 46%, 42%, and 35% in the sunitinib. Grade 3 or 4 TRAEs were reported at rates of 68% and 55% in the investigational and control arms, respectively.

“The committee concluded that cabozantinib plus nivolumab is an effective treatment for RCC. The committee heard from patients and clinical experts that further treatment options would be appreciated. The most plausible cost-effectiveness estimates for all- and favorable-risk cancer were above what NICE considers an acceptable use of NHS resources for all comparators. But, when considering the most appropriate comparators for intermediate- and poor-risk cancer, the most plausible cost-effectiveness estimates were within what NICE considers acceptable,” NICE wrote in conclusion.1


  1. National Institute for Health and Care Excellence. Cabozantinib with nivolumab for untreated advanced renal cell carcinoma. Final draft guidance. March 2024. Accessed March 28, 2024.
  2. Bourlon MT, Escudier B, Burotto M, et al. Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): results from 55-month follow-up of the CheckMate 9ER trial. J Clin Oncol. 2024;42(suppl 4):362. doi:10.1200/JCO.2024.42.4_suppl.362
  3. NICE recommends Cabometyx (cabozantinib) in combination with OPDIVO (nivolumab) for advanced kidney cancer. News release. Ipsen. March 7, 2024. Accessed March 28, 2024.,if%20their%20disease%20is%20intermediate
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