Patient-reported outcomes with first-line nivolumab plus cabozantinib versus sunitinib in patients with advanced renal cell carcinoma treated in CheckMate 9ER: an open-label, randomised, phase 3 trial
Mené dans 18 pays sur 651 patients atteints d'un carcinome à cellules rénales de stade avancé, cet essai de phase III évalue l'intérêt, du point de vue des symptômes déclarés par les patients, d'un traitement de première ligne combinant nivolumab et cabozantinib par rapport au sunitinib en monothérapie
Background : In the CheckMate 9ER trial, patients with advanced renal cell carcinoma who receivedfirst-line nivolumab plus cabozantinib had significantly better progression-free survival compared with those given sunitinib. In this study, we aimed to describe the patient-reportedoutcome (PRO) results from CheckMate 9ER. Methods : In this open-label, randomised, phase 3 trial done in 125 cancer centres, urologycentres, and hospitals across 18 countries, patients aged 18 years or older with previouslyuntreated advanced renal cell carcinoma with a clear-cell component, a Karnofsky performancestatus of 70% or more, and available tumour tissue were randomly assigned (1:1) viainteractive response technology to nivolumab 240 mg intravenously every 2 weeks plusoral cabozantinib 40 mg per day, or oral sunitinib 50 mg per day monotherapy for 4weeks in 6-week cycles. The primary endpoint of progression-free survival was reportedpreviously. PROs were analysed as prespecified exploratory endpoints at common timepoints(at baseline and every 6 weeks) until week 115. Disease-related symptoms were evaluatedusing the 19-item Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19),and global health status was assessed with the three-level EQ-5D (EQ-5D-3L) visualanalogue scale (VAS) and UK utility index. PRO analyses were done in the intention-to-treatpopulation. Change from baseline was assessed using mixed-model repeated measures.A time-to-deterioration analysis was done for first and confirmed deterioration events.This study is registered with ClinicalTrials.gov, NCT03141177, and is closed to recruitment. Findings : Between Sept 11, 2017, and May 14, 2019, 323 patients were randomly assigned to nivolumabplus cabozantinib and 328 to sunitinib. Median follow-up was 23·5 months (IQR 21·0–26·5).At baseline, patients in both groups reported low symptom burden (FKSI-19 disease-relatedsymptoms version 1 mean scores at baseline were 30·24 [SD 5·19] for the nivolumabplus cabozantinib group and 30·06 [5·03] for the sunitinib group). Change from baselinein PRO scores indicated that nivolumab plus cabozantinib was associated with morefavourable outcomes versus sunitinib (treatment difference 2·38 [95% CI 1·20–3·56],nominal p<0·0001, effect size 0·33 [95% CI 0·17–0·50] for FKSI-19 total score; 1·33[0·84–1·83], nominal p<0·0001, 0·45 [0·28–0·61] for FKSI-19 disease-related symptomsversion 1; 3·48 [1·58–5·39], nominal p=0·0004, 0·30 [0·14–0·47] for EQ-5D-3L VAS;and 0·04 [0·01–0·07], nominal p=0·0036, 0·25 [0·08–0·41] for EQ-5D-3L UK utility index),reaching significance at most timepoints. Nivolumab plus cabozantinib was associatedwith decreased risk of clinically meaningful deterioration for FKSI-19 total scorecompared with sunitinib (first deterioration event hazard ratio 0·70 [95% CI 0·56–0·86],nominal p=0·0007; confirmed deterioration event 0·63 [0·50–0·80], nominal p=0·0001). Interpretation : PROs were maintained or improved with nivolumab plus cabozantinib versus sunitinib.Compared with sunitinib, nivolumab plus cabozantinib significantly delayed time todeterioration of patient-reported outcome scores. These results suggest a benefitfor nivolumab plus cabozantinib compared with sunitinib in the treatment of patientswith advanced renal cell carcinoma.