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Avelumab plus cetuximab and radiotherapy (AC-RT) is no more effective than standard care for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), according to research presented at the European Society for Medical Oncology (ESMO) Congress 2021.1
The results, from the phase 3 GORTEC-REACH trial (ClinicalTrials.gov Identifier: NCT02999087), were presented by Jean Bourhis, MD, PhD, of Lausanne University Hospital in Switzerland.
Dr Bourhis explained that avelumab can induce antibody-dependent cell-mediated cytotoxicity in addition to inhibiting PD-1/PD-L1 interactions. Thus, avelumab may have a synergistic effect with cetuximab.
With that in mind, the GORTEC-REACH trial was designed to compare AC-RT with standard of care (SOC) for LA-SCCHN. The trial included 707 patients with previously untreated, unresected, stage III-IV LA-SCCHN. Patients were first divided into 2 cohorts: those deemed fit to receive high-dose cisplatin (60%) and those considered unfit for cisplatin (40%).
Patients were then randomly assigned to receive SOC or AC-RT. SOC consisted of intensity-modulated RT (70 Gy/6.5 weeks) plus cisplatin in fit patients or the same RT regimen plus cetuximab in patients who were unfit for cisplatin.
AC-RT, which was given to cisplatin-fit and -unfit patients, consisted of intensity-modulated RT (70 Gy/6.5 weeks), weekly cetuximab, and avelumab given at day 7 and then every 2 weeks during RT, followed by avelumab for 12 months.
There were 275 evaluable cisplatin-unfit patients who were randomly assigned to the AC-RT arm (140 patients) or the SOC arm (135 patients).
Baseline characteristics were well balanced between the treatment arms, Dr Bourhis said. Overall, 79% of patients were men, the median age was 67 years, 88% were current or former smokers, 61% had oropharyngeal tumors, and stage IVa disease was most common stage (56%).
The median follow-up was 21.3 months in both treatment arms.
The 2-year progression-free survival (PFS) rate was numerically higher in the AC-RT arm than in the SOC arm — 44% and 31%, respectively — but the difference was not statistically significant (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.62-1.15; P =.14).
Similarly, the cumulative incidence of loco-regional progression was numerically lower in the AC-RT arm than in the SOC arm — 34% and 44%, respectively — but the difference was not significant (aHR, 0.83; 95% CI, 0.56-1.22; P =.34).
On the other hand, the cumulative incidence of distant metastases was significantly lower in the AC-RT arm than in the SOC arm — 5.4% and 14.3%, respectively (adjusted aHR, 0.31; 95% CI, 0.13-0.72; P =.007).
Dr Bourhis noted that there was a nonsignificant increase in deaths without progression observed in the AC-RT arm, “without direct toxicity of avelumab.”
The cumulative incidence of death was 16% in the AC-RT arm and 11% in the SOC arm (aHR, 1.81; 95% CI, 0.90-3.6; P =.1). The 2-year overall survival rate was 58% and 54%, respectively (aHR, 1.08; 95% CI, 0.73-1.6; P =.69).
Grade 3 or higher adverse events (AEs) were reported in 80% of patients in both treatment arms (P =.91). The most common of these were dermatitis, mucositis, and dysphagia.
However, there were 10 grade 5 AEs in the AC-RT arm and 3 in the SOC arm. Causes of death in the SOC arm included tumor bleeding, early cancer progression, and unknown cause (1 patient each).
Causes of death in the AC-RT arm included decompensation of pre-existing comorbidities (3 patients), infection (2 patients), tumor bleeding (2 patients), early cancer progression (1 patient), and unknown causes (2 patients).
Among the 430 cisplatin-fit patients, the number of PFS events was not reached at the time of analysis.
The planned interim analysis for futility based on 89 events in 317 patients showed a 1-year PFS rate of 64% in the AC-RT arm and 73% in the SOC arm. Dr Bourhis noted that this crossed the futility boundary (HR, 1.27; 95% CI, 0.83-1.93).
“The GORTEC-REACH study does not change the standard of care in locally advanced head and neck squamous cell carcinoma,” said study discussant Amanda Psyrri, MD, PhD, of National Kapodistrian University of Athens in Greece.
“The results of the study for cisplatin-fit patients agree with those of the JAVELIN Head and Neck 100 study.2 For cisplatin-unfit patients, a signal of activity was demonstrated in the avelumab arm, but this was not translated to a statistically significant prolongation of PFS.”
Disclosures: This research was supported by Merck Serono S.A.S. The study authors declared no conflicts of interest, but Dr Psyrri disclosed affiliations with Merck Serono, Roche, AstraZeneca, Bristol Myers Squibb, Bayer, Pfizer, Medscape, Kura Oncology, Genesis, and Boehringer Ingelheim.
- Bourhis J, Tao Y, Sun X, et al. Avelumab-cetuximab-radiotherapy versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Randomized phase III GORTEC-REACH trial. Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract LBA35.
- Lee NY, Ferris RL, Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: A randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450-462. doi:10.1016/S1470-2045(20)30737-3