Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended follow-up from the phase III randomised CheckMate 9ER trial

Abstract

Background: Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score.

Patients and methods: Patients with treatment-naïve aRCC received NIVO 240 mg every 2 weeks plus CABO 40 mg once daily or SUN 50 mg for 4 weeks (6-week cycles), until disease progression/unacceptable toxicity (maximum NIVO treatment, 2 years). Primary endpoint was progression-free survival (PFS) per blinded independent central review (BICR). Secondary endpoints were overall survival (OS), objective response rate (ORR) per BICR, and safety and tolerability.

Results: Overall, 323 patients were randomised to NIVO + CABO and 328 to SUN. Median PFS was improved with NIVO + CABO versus SUN [16.6 versus 8.4 months; hazard ratio (HR) 0.59; 95% confidence interval (CI) 0.49-0.71]; median OS favoured NIVO + CABO versus SUN (49.5 versus 35.5 months; HR 0.70; 95% CI 0.56-0.87). ORR (95% CI) was higher with NIVO + CABO versus SUN [56% (50% to 62%) versus 28% (23% to 33%)]; 13% versus 5% of patients achieved complete response, and median duration of response was 22.1 months versus 16.1 months, respectively. PFS and OS favoured NIVO + CABO over SUN across intermediate, poor and intermediate/poor IMDC risk subgroups; higher ORR and complete response rates were seen with NIVO + CABO versus SUN regardless of IMDC risk subgroup. Any-grade (grade ≥3) treatment-related adverse events occurred in 97% (67%) versus 93% (55%) of patients treated with NIVO + CABO versus SUN.

Conclusions: After extended follow-up, NIVO + CABO maintained survival and response benefits; safety remained consistent with previous follow-ups. These results continue to support NIVO + CABO as a first-line treatment for aRCC.

Trial registration: ClinicalTrials.gov, NCT03141177.

Keywords: IMDC; cabozantinib; immunotherapy; nivolumab; phase III; renal cell carcinoma.

Figure 1

PFS per BICR in the (A) ITT population and by IMDC favourable (B), intermediate (C), poor (D) and intermediate/poor combined (E) risk group (IRT). BICR, blinded independent central review; CI, confidence interval; HR, hazard ratio; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; IRT, interactive response technology; ITT, intent-to-treat; NIVO + CABO, nivolumab plus cabozantinib; PFS, progression-free survival; SUN, sunitinib.^aStratified Cox proportional hazard model used for HR. ^bUnstratified Cox proportional hazard model used for HR.

Figure 2

OS in the (A) ITT population and by IMDC favourable (B), intermediate (C), poor (D) and intermediate/poor combined (E) risk group (IRT). CI, confidence interval; HR, hazard ratio; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; IRT, interactive response technology; ITT, intent-to-treat; NE, not estimable; NIVO + CABO, nivolumab plus cabozantinib; NR, not reached; OS, overall survival; SUN, sunitinib.^aStratified Cox proportional hazard model used for HR. ^bUnstratified Cox proportional hazard model used for HR.

Figure 3

Treatment-related AEs in ≥20% of all treated patients. AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; NIVO + CABO, nivolumab plus cabozantinib; PPE; palmar–plantar erythrodysaesthesia; SUN, sunitinib.^aNo patients had a grade 5 event with NIVO + CABO and one patient had a grade 5 event with SUN. ^bTotal bar represents treatment-related AEs of any grade in either treatment arm reported between first dose and 30 days after last dose of study therapy; of these events, none were grade 5.