In patients with advanced renal cell carcinoma (aRCC) and bone metastasis, treatment with first-line nivolumab plus cabozantinib improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) relative to treatment with sunitinib, according to research presented at the International Kidney Cancer Symposium (IKCS) 2021.

The investigators conducted a post-hoc exploratory analysis of outcomes by baseline bone metastasis status (per investigator) in subgroups of patients from the phase 3 CheckMate 9ER trial ( Identifier: NCT03141177), which previously demonstrated the efficacy benefits of nivolumab plus cabozantinib vs sunitinib in first-line aRCC.

A total of 651 patients with clear cell aRCC were randomly assigned (1:1) to receive nivolumab plus cabozantinib (240 mg Q2W; 40 mg QD) or sunitinib (50 mg QD for 4 weeks of 6-week cycles). PFS and ORR were evaluated per blinded independent central review. The data cut-off date was September 10, 2020. Median follow-up duration was 23.5 months (range, 16.0-36.0).

Continue Reading

Overall, 151 patients had bone metastasis at baseline, 79 in the nivolumab plus cabozantinib arm and 72 in the sunitinib arm (patients without bone metastasis at baseline: n=244 nivolumab plus cabozantinib, n=256 sunitinib). Across the subgroups, the median age was 61 to 63 years (range, 29-90), and patients were mostly White (79%-90%) and male (70%-77%).

Regardless of bone metastasis, ORR was higher with nivolumab plus cabozantinib than sunitinib (with bone metastasis: 48% vs 11%; without bone metastasis: 57% vs 33%). Duration of objective response was longer with nivolumab plus cabozantinib compared with sunitinib (with bone metastasis: 18% vs 7%; without bone metastasis: 22% vs 13%).

PFS was longer with nivolumab plus cabozantinib compared with sunitinib in patients with bone metastasis (18.2 vs 4.4 months; hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.25-0.59) and without bone metastasis (17 vs 9.5 months; HR, 0.57; 95% CI, 0.45-0.72). HR for OS also favored nivolumab plus cabozantinib over sunitinib in patients with (HR, 0.64; 95% CI, 0.39–1.06) or without bone metastasis (HR, 0.65; 95% CI, 0.46–0.91). Median duration of treatment was longer with nivolumab plus cabozantinib compared with sunitinib regardless of subgroup (with bone metastasis: 16.2 vs 5.8 months; without bone metastasis: 18.6 vs 10.4 months).

With nivolumab plus cabozantinib vs sunitinib, all-cause grade 3 to 4 adverse events in patients with bone metastasis were 78% vs 67% and in those without bone metastasis were 71% vs 68%, respectively; treatment-related grade 3 to 4 adverse events were 71% vs 42% and 59% vs 55%, respectively.

“In this post-hoc exploratory analysis, treatment with [nivolumab plus cabozantinib] vs [sunitinib] improved PFS, OS, and ORR in patients with first-line aRCC irrespective of bone metastasis at baseline, consistent with outcomes reported in all randomized patients,” the investigators concluded.

Disclosure: This research was sponsored by Bristol Myers Squibb (Princeton, NJ, USA) in collaboration with Exelixis, Inc. (Alameda, CA,USA), Ipsen Pharma (Paris, France), Ono Pharmaceutical Company Ltd. (Osaka, Japan) and Takeda Pharmaceutical (Osaka, Japan). Please see the original reference for a full list of authors’ disclosures.


Apolo A, Powles T, Bourlon MT, et al. Nivolumab plus cabozantinib (N+C) versus sunitinib (S) in patients with advanced renal cell carcinoma (aRCC) and bone metastasis: subgroup analysis of the phase 3 CheckMate 9ER trial. Presented at IKCS 2021; November 5-6, 2021. Abstract N22.