Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression

Highlights

• Nivolumab showed prolonged OS benefit in patients with R/M SCCHN post-platinum.

• Long-term OS benefit was observed irrespective of PD-L1 expression or HPV status.

• No new safety concerns were identified from long-term nivolumab treatment.

Abstract

Objectives

We report 2-year results from CheckMate 141 to establish the long-term efficacy and safety profile of nivolumab and outcomes by tumor PD-L1 expression in patients with recurrent or metastatic (R/M),platinum-refractory squamous cell carcinoma of the head and neck (SCCHN).

Methods

Patients with R/M SCCHN with tumor progression/recurrence within 6 months of platinum therapy were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator’s choice (IC). Primary endpoint: overall survival (OS). Data cutoff: September 2017.

Results

With 24.2 months’ minimum follow-up, nivolumab (n = 240) continued to improve OS vs IC (n = 121), hazard ratio (HR) = 0.68 (95% CI 0.54–0.86). Nivolumab nearly tripled the estimated 24-month OS rate (16.9%) vs IC (6.0%), and demonstrated OS benefit across patients with tumor PD-L1 expression ≥1% (HR [95% CI] = 0.55 [0.39–0.78]) and  < 1% (HR [95% CI] = 0.73 [0.49–1.09]), and regardless of tumor HPV status. Estimated OS rates at 18, 24, and 30 months with nivolumab were consistent irrespective of PD-L1 expression (<1%/≥1%). In the nivolumab arm, there were no observed differences in baseline characteristics or safety profile between long-term survivors and the overall population. Grade 3–4 treatment-related adverse event rates were 15.3% and 36.9% for nivolumab and IC, respectively.

Conclusion

Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up. OS benefit was observed with nivolumab irrespective of PD-L1 expression and HPV status. (Clinicaltrials.gov: NCT02105636)

Introduction

Squamous cell carcinoma of the head and neck (SCCHN) includes neoplasms in the oral cavity, pharynx, and larynx, and accounts for 90% of all head and neck cancers [1], [2], [3]. Patients with recurrent/metastatic (R/M) SCCHN who progress within 6 months after platinum-based therapy have poor long-term prognosis and limited treatment options, with a median overall survival (OS) of ≤6 months [4], [5]. In 2016, nivolumab was approved in the United States for the treatment of this patient population, with European approval following in 2017 [6], [7].

CheckMate 141 evaluated the efficacy, safety, and patient-reported quality of life of nivolumab monotherapy vs standard single agent of investigator’s choice (IC) in patients with R/M SCCHN who experienced tumor progression or recurrence within 6 months of platinum-based therapy administered in the adjuvant, primary (ie, with radiation), recurrent, or metastatic setting [8], [9]. Nivolumab is the only immunotherapy to significantly improve OS at the primary analysis in this patient population, hazard ratio (HR) vs IC = 0.70 (97.73% confidence interval [CI] 0.51–0.96); p = 0.01 [8]. With 1-year follow-up, nivolumab continued to improve OS compared with IC; HR = 0.71 (95% confidence interval [CI]: 0.55, 0.90) [10]. The Kaplan-Meier–estimated 18-month OS rate with nivolumab was nearly triple that with IC (21.5% vs 8.3%). The objective response rate (ORR) with nivolumab was more than twice that of IC (13.3% vs 5.8%). The safety profile of nivolumab was manageable, with fewer grade 3–4 treatment-related adverse events (TRAEs) compared with IC. Nivolumab also stabilized quality-of-life measures, whereas clinically meaningful deterioration was observed with IC [9]. Here, we report long-term (2-year) follow-up of CheckMate 141 in the overall population, as well as in subgroups defined by baseline tumor programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status.