Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial

• Published in: The lancet oncology 2019-02, Vol.20 (2), p.297-310
• Main Authors: Cella, David, Grünwald, Viktor, Escudier, Bernard, Hammers, Hans J, George, Saby, Nathan, Paul, Grimm, Marc-Oliver, Rini, Brian I, Doan, Justin, Ivanescu, Cristina, Paty, Jean, Mekan, Sabeen, Motzer, Robert J
• Format: Article
• Language: English
• Subjects: Cancer therapies; Clear cell-type renal cell carcinoma; Clinical medicine; Clinical outcomes; FDA approval; Immunotherapy; Inhibitor drugs; Kidney cancer; Medical prognosis; Metastases; Metastasis; Monoclonal antibodies; Patients; Quality of life; Regulatory approval; Targeted cancer therapy
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(18)30778-2

In the ongoing phase 3, CheckMate 214 trial, nivolumab plus ipilimumab improved overall survival compared with sunitinib in patients with intermediate or poor risk, previously untreated, advanced renal cell carcinoma. We aimed to assess whether health-related quality of life (HRQoL) could be used to further describe the benefit-risk profile of nivolumab plus ipilimumab versus sunitinib. In the phase 3, randomised, controlled, CheckMate 214 trial, patients aged 18 years and older with previously untreated, advanced or metastatic renal cell carcinoma with a clear-cell component were recruited from 175 hospitals and cancer centres in 28 countries. Patients were categorised by risk status into favourable, intermediate, and poor risk subgroups and randomly assigned (1:1) to open-label nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab 3 mg/kg every 2 weeks, or sunitinib 50 mg/day for 4 weeks of each 6-week cycle. Randomisation was done with a block size of four and stratified by risk status and geographical region. Patient-reported outcomes (PROs) were assessed using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), Functional Assessment of Cancer Therapy-General (FACT-G), and EuroQol five dimensional three level (EQ-5D-3L) instruments. The coprimary endpoints of the trial, reported previously, were overall survival, progression-free survival, and the proportion of patients who had an objective response in those categorised as at intermediate or poor risk. PROs in all randomised participants were assessed as an exploratory endpoint; here we report this exploratory endpoint. This study is registered with ClinicalTrials.gov, number NCT02231749, and is ongoing but is now closed to recruitment. Between Oct 16, 2014, and Feb 23, 2016, of 1390 patients screened, 1096 (79%) were randomly assigned to treatment, of whom 847 (77%) were at intermediate or poor risk and randomly assigned to nivolumab plus ipilimumab (n=425) or sunitinib (n=422). Median follow-up was 25·2 months (IQR 23·0–27·4). PROs were more favourable with nivolumab plus ipilimumab than sunitinib throughout the first 103 weeks after baseline, with mean change from baseline at week 103 for FKSI-19 total score being 4·00 (95% CI 1·91 to 6·09) for nivolumab plus ipilimumab versus −3·14 (−6·03 to −0·25) for sunitinib (p