Nivolumab combined with cabozantinib is associated with superior oncologic outcomes and overall survival (OS) compared with sunitinib monotherapy for the first-line treatment of advanced renal cell carcinoma (aRCC), according to data presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

The data are the first results from the randomized phase 3 CheckMate 9ER trial in which investigators led by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, randomly assigned 651 patients with clear cell aRCC to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). The primary endpoint was progression-free survival (PFS); secondary endpoints included OS and objective response rate (ORR). PFS and ORR were determined by independent central review.

Dr Choueiri’s team noted that both nivolumab, a checkpoint inhibitor, and cabozantinib, a tyrosine kinase inhibitor, have shown efficacy and a manageable safety profile in the treatment of aRCC. Cabozantinib, they explained, has immunomodulatory properties that may counteract tumor-induced immunosuppression, thus providing a rationale for using both drugs in combination.

Continue Reading

Study participants had a median follow-up of 18.1 months (minimum 10.6 months). Compared with sunitinib monotherapy, nivolumab plus cabozantinib treatment was significantly associated with a 49% decreased risk for progression, with a median time to progression of 16.6 months for the combination therapy arm compared with 8.3 months in the sunitinib arm (P <.0001). The combination treatment was significantly associated with a 40% decreased risk for death compared with sunitinib monotherapy, with median survival times not reached (P =.0010). Results were consistent across prespecified International Metastatic RCC Database Consortium (IMDC) risk and PD-L1 subgroups.

The ORR was significantly higher in the combination arm than among sunitinib recipients (55.7% vs 27.1%; P <.0001). A significantly higher proportion of patients in the combination than monotherapy arm achieved a complete response (8.0% vs 4.6%).

In addition, the median duration of response was significantly longer for the nivolumab-cabozantinib than sunitinib arm (20.2 vs 11.5 months).

Dr Choueiri and his colleagues concluded that the safety profile of the combination therapy was manageable and consistent with the adverse event (AE) profiles of nivolumab and cabozantinib use as single agents.

Grade 3 or higher treatment-related AEs (TRAEs) occurred in 60.6% of the combination arm compared with 50.9% of the sunitinib arm. One treatment-related death occurred in the combination arm and 2 occurred among the sunitinib recipients.

Discontinuation of study drugs because of TRAEs occurred in 3.1% of patients in the combination arm and 8.8% of those in the sunitinib arm.

Of the 651 patients in the study, 22.6%, 57.6%, and 19.7% had IMDC favorable-, intermediate-, and poor-risk disease, respectively. In addition, 24.9% of patients had PD-L1 expression of 1% of higher.

In an ESMO press release, Dominik Berthold, MD, Head, Specialised Consultation for Urological Cancers Medical Oncology Service, Department of Oncology, Lausanne University Hospital, Switzerland commented: “CheckMate 9ER met its efficacy endpoints and the combination can be considered a new first-line treatment option.”

Disclosure: Funding for the study was provided by Bristol-Myers Squibb Company of Princeton, New Jersey, ONO Pharmaceutical Company Ltd, of Osaka, Japan, and Exelixis Inc., of Alameda, California.


Choueiri TK, Powles T, Burotto M, et al. Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial. Presented at: ESMO Virtual Congress 2020. Abstract 696O-PR.