Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial

Abstract

Summary Background Patients with platinum-refractory recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) have limited treatment options and poor prognosis. Nivolumab significantly improved survival of this patient population when compared with standard single-agent therapy of investigator’s choice (IC) in Checkmate 141; here we report the impact of nivolumab on patient-reported outcomes (PROs). Methods CheckMate 141 (NCT02105636) was a randomised, open-label, phase 3 trial in patients with R/M SCCHN who progressed within 6 months after platinum-based chemotherapy. Patients were randomised 2:1 to nivolumab 3 mg/kg every 2 weeks (n=240) or IC (n=121) of methotrexate (40–60 mg/m2 of body surface area), docetaxel (30–40 mg/m2), or cetuximab (250 mg/m2 after a loading dose of 400 mg/m2). On 26 January 2016, the independent data monitoring committee reviewed the data at the planned interim analysis and declared overall survival superiority for nivolumab over IC therapy (primary endpoint; described previously). The protocol was amended to allow patients in the IC arm to cross over to nivolumab. All patients not on active therapy are being followed for survival. As an exploratory endpoint, PROs were assessed at baseline, week 9, and every 6 weeks thereafter using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Core 30 (QLQ-C30), the EORTC head and neck cancer–specific module (EORTC QLQ-H&N35), and the three-level European Quality of Life–5 Dimensions (EQ-5D) questionnaire. Differences within and between treatment arms in PROs were analysed by analyses of covariance (ANCOVA) among patients with baseline and ≥1 other assessment (n=129). Among all randomised patients (N=361), median time to clinically meaningful deterioration was analysed by Kaplan-Meier methods. Findings Treatment with nivolumab resulted in adjusted mean changes from baseline to week 15 ranging from −2·1 to +5·4 across functional and symptom domains measured by the EORTC QLQ-C30, with no domains indicating clinically meaningful deterioration. In contrast, 8 (53%) of the 15 domains in the IC arm demonstrated clinically meaningful deterioration (10 points or more) at week 15 (change from baseline range, −24·5 to +2·4). Similarly, on the EORTC QLQ-H&N35, clinically meaningful worsening at week 15 was seen in 0 domains in the nivolumab arm and 8 (44%) of 18 domains in the IC arm. Patients in the nivolumab arm experienced a clinically meaningful improvement (according to a difference of 7 points or greater) in adjusted mean change from baseline to week 15 on the EQ-5D visual analogue scale, in contrast to a clinically meaningful deterioration in the IC arm (+7·3 vs −7·8). Differences between arms were statistically significant and clinically meaningful at weeks 9 and 15 in favour of nivolumab for role functioning, social functioning, fatigue, dyspnoea, and appetite loss on the EORTC QLQ-C30 and pain and sensory problems on the EORTC QLQ-H&N35. Median time to deterioration was significantly longer with nivolumab vs IC for 13 (37%) of 35 domains assessed across the three questionnaires. Interpretation In this exploratory analysis of CheckMate 141, nivolumab stabilised symptoms and functioning from baseline to weeks 9 and 15, whereas IC led to clinically meaningful deterioration. Nivolumab delayed time to deterioration of patient-reported quality-of-life outcomes compared with single-agent therapy of IC in patients with platinum-refractory R/M SCCHN. Given the significant unmet need in this population and the importance of maintaining or improving quality of life for patients with R/M SCCHN, these data support nivolumab as a new standard-of-care option in this setting. Funding Bristol-Myers Squibb.