ESMO 2020

First results of the phase 3 CheckMate 9ER trail, comparing first-line treatment of advanced renal cell carcinoma (RCC) with cabozantinib and nivolumab to treatment with sunitinib, showed both favourable efficacy and safety for the combination therapy.

The checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor cabozantinib are each approved as single agent therapies for treatment of patients with advanced clear cell RCC, based on improvements in overall survival (OS) in phase 3 clinical trials [1,2]. In a phase 1 study in patients with advanced genitourinary malignancies, the combination of nivolumab and cabozantinib showed promising preliminary antitumor activity, providing a rationale for this combination. At ESMO Virtual 2020, Dr Toni Choueiri (Dana-Farber Cancer Institute, USA) presented the first results of CheckMate 9ER, a phase 3 trial comparing the combination therapy to treatment with sunitinib [3].

A total of 651 patients (22.6% favourable risk, 57.6% intermediate risk, 19.7% poor risk; 24.9% PD-L1 ≥1%) were 1:1 randomised to nivolumab (240 mg flat dose Q2W) plus cabozantinib (40 mg QD), or sunitinib (50 mg QD, 4 weeks on/2 weeks off). Primary endpoint of the ongoing study is progression-free survival (PFS) by blinded independent central review (BICR). Secondary endpoints are overall survival (OS), objective response rate (ORR), and safety.

With 18.1 months median follow-up, all 3 efficacy endpoints were met. Nivolumab plus cabozantinib significantly improved PFS with a median PFS of 16.6 months versus 8.3 months with sunitinib (HR 0.51; P<0.0001). The benefit of nivolumab plus cabozantinib was observed in all prespecified subgroups. Median OS was not yet reached in both study arms, but current HR was 0.60 (95% CI 0.40-0.89; P=0.010) in favour of nivolumab plus cabozantinib. ORR was significantly higher with nivolumab plus cabozantinib: 55.7% versus 27.1%, respectively (P< 0.0001). A complete response was achieved in 8.0% and 4.6% of the patients, respectively. Median duration of response was 20.2 versus 11.5 months for nivolumab plus cabozantinib versus sunitinib. Health-related quality of life appeared to be better in the nivolumab plus cabozantinib arm compared with the sunitinib arm. Nivolumab plus cabozantinib was well tolerated with a low rate of treatment-related discontinuations.