Progression-free survival (PFS) and overall survival (OS) in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) were not improved by a regimen of avelumab plus chemoradiotherapy (CRT) followed by avelumab maintenance over placebo plus CRT and placebo maintenance, according to interim analysis findings from the phase III JAVELIN head & neck 100 study presented at ESMO Virtual Congress 2020 by Ezra E. Cohen of the Moores Cancer Centre, University of California in La Jolla, USA.
This randomised, double-blind, placebo-controlled phase III study sought to determine whether avelumab and concurrent CRT followed by avelumab maintenance could delay progression, as the LA SCCHN recurs in many patients after high-dose, cisplatin-containing, multimodality therapy.
JAVELIN enrolled 697 patients with histologically confirmed, previously untreated LA SCCHN of the oropharynx, hypopharynx, larynx, or oral cavity who were eligible for definitive CRT with curative intent. Further study requirements included stage III, IVa, or IVb disease per AJCC (7th edition) except for patients with human papillomavirus-positive oropharyngeal cancer, for whom only T4 or N2c or N3 status was allowed.
Following 1:1 randomisation, 350 patients were assigned to receive avelumab at 10 mg/kg i.v. every two weeks plus CRT comprising cisplatin at 100 mg/m2 every three weeks plus standard fractionation of 70 Gy in 35 fractions over 7 weeks and 347 patients were assigned to receive placebo plus the same CRT. Both arms received a lead-in dose and avelumab or placebo maintenance therapy for up to 1 year. The patients’ baseline characteristics were similar in both arms.
The primary endpoint of JAVELIN was PFS by investigator assessment per modified RECIST v1.1 and the interim analysis was planned at approximately 217 events.
The interim analysis showed no significant improvement with the addition of avelumab
At the time of the interim analysis 224 PFS and 131 OS events had occurred.
Neither median PFS nor OS were reached in either treatment arm. The hazard ratio (HR) for PFS favoured placebo plus CRT (HR, 1.21; 95% confidence interval [CI] 0.93-1.57; 1-sided p = 0.920). The OS results similarly were in favour of placebo/CRT (HR 1.31; 95% CI 0.93-1.85; 1-sided p = 0.937).
Adverse events (AEs) Grade ≥3 were reported more frequently with avelumab plus CRT (88%) compared with 82% in patients on placebo/CRT. Fatal AEs occurred in 6% of patients on avelumab/CRT and 5% of patients receiving placebo/CRT; 33% versus 32% of patients, respectively, discontinued study drug due to AEs.
The investigators summarised that tolerability was similar in both arms. They further concluded that, although the study did not demonstrate statistically significant improvement in PFS with avelumab plus CRT compared with placebo plus CRT, these results may inform future trial design.
Funding for this study was reported from Pfizer, as part of an alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.
910O – Cohen EE, Ferris RL, Psyrri A, et al. Primary results of the phase III JAVELIN head & neck 100 trial: Avelumab plus chemoradiotherapy (CRT) followed by avelumab maintenance vs CRT in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). ESMO Virtual Congress 2020.