Based on findings from the phase 3 CheckMate 9ER trial, the FDA approved nivolumab/cabozantinib for use in the first-line setting for patients with advanced RCC.
Findings from an exploratory analysis of the pivotal phase 3 CheckMate 9ER trial showed that frontline treatment with nivolumab (Opdivo) plus cabozantinib (Cabometyx) enhanced health-related quality of life (HRQoL) compared with sunitinib (Sutent) in patients with advanced renal cell carcinoma (RCC).1
The QoL data, which were presented during the 2021 ASCO Genitourinary Cancers Symposium, also showed that, in the cohort of patients receiving the combination of the PD-1 inhibitor and the multikinase inhibitor, there was a delay in deterioration and a significant decreased risk for confirmed deterioration in HRQoL scores, including disease-related kidney cancer symptoms.
“These results indicate that the superior clinical efficacy of (nivolumab plus cabozantinib) over (sunitinib) is accompanied by the additional benefit of better HRQoL,” the researchers wrote. “Moreover, the HRQoL outcomes also support the acceptable tolerability profile of the (nivolumab plus cabozantinib) combination for patients with advanced HRQoL.”
Based on findings from the CheckMate 9ER trial, the FDA approved nivolumab/cabozantinib in January 2021 for use in the first-line setting for patients with advanced RCC.
In CheckMate 9ER, after a median follow-up of 18.1 months, nivolumab plus cabozantinib demonstrated superior progression free survival (hazard ratio [HR], 0.51; P <.0001), overall survival (HR, 0.60; P = .001) and objective response rate (P <.0001), compared with sunitinib, in patients with advanced RCC with a clear cell component.
In their presentation, the researchers investigated patient-reported HRQoL outcomes further, including overall between-group comparisons of treatment groups and time to confirmed deterioration outcomes.
“In addition to the clinical outcomes, analyses of HRQoL, including time to confirmed deterioration in patient-reported outcome (PRO) scores may provide important insights for clinicians to assess the benefit/risk profile of potential new treatment regimens,” the researchers wrote.
To be eligible for the phase 3 trial, patients had to have previously untreated, advanced or metastatic RCC; a clear cell component; and any International Metastatic RCC Database Consortium (IMDC) risk. Patients were then stratified by IMDC risk score, tumor PD-L1 expression, and geographic region.
In total, patients were randomized 1:1 to receive either nivolumab at 240 mg IV every 2 weeks plus oral cabozantinib 40 mg daily (n = 323) or oral sunitinib at 50 mg daily for 4 weeks on, 2 weeks off (n = 328), until disease progression or toxicity.
PRO instruments were administered before treatment, and included Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19) and the 3-level version of the EQ-5D (EQ-5D-3L). PRO completion rates for both arms were at 93% or more at baseline, and completion rates remained at 80% or more through week 91.
Longitudinal score changes from baseline in FKSI-19 total score and FKSI-19 disease-related symptom (DRS) scores favored nivolumab plus cabozantinib, compared to sunitinib, with an overall mean change from baseline of 2.90 (-0.51 vs -3.40; P <.0001) and 1.55 (+0.77 vs -0.78; P <.0001), respectively.
Mean change in EQ-5D-3L utility index and visual analog scale (VAS) scores also favored nivolumab plus cabozantinib, showing significant change through treatment with an overall change of 0.05 (-0.02 vs -0.07; P = .0005) and 3.26 (+2.02 vs -1.24; P = .0011), respectively, with the combination versus sunitinib.
There was also a significant decreased risk of confirmed deterioration with nivolumab plus cabozantinib in FKSI-19 total score (HR, 0.64; 95% CI, 0.50-0.81; P = .0003) and FKSI-19 DRS score (HR, 0.62; 95% CI, 0.46-0.82; P = .0006).
1. Cella D, Choueiri t, Blum S, et al. Patient-Reported Outcomes of Patients with Advanced Renal Cell Carcinoma Treated with First-Line Nivolumab Plus Cabozantinib Versus Sunitinib: the CheckMate 9ER Trial. Presented at: 2021 ASCO Genitourinary Cancer Symposium; February 11-13, 2021; Virtual. Abstract 285.