854MO - Avelumab-cetuximab-radiotherapy (RT) versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Final analysis of randomized phase III GORTEC 2017-01 REACH trial

Background

Based on a potential synergistic effect of anti–PD-L1 avelumab plus cetuximab and RT, this combination was tested in a randomized trial against two standards of care (SOC) in LA-SCCHN.

Methods

The trial comprised 2 cohorts of patients (pts): fit for cisplatin (100 mg/m², Q3W) and unfit for cisplatin. The SOC was IMRT 70 Gy / 6.5 weeks with cisplatin in fit Cohort and with cetuximab in unfit Cohort (Bonner, 2006). In both cohorts, experimental arm (Exp) was IMRT 70 Gy plus weekly cetuximab and avelumab 10 mg/kg at Day-7 and every 2 weeks during RT followed by avelumab every 2 weeks for 1 year. The primary endpoint was progression-free survival (PFS). In unfit Cohort, 115 events were needed / 277 pts to detect a HR of 0.62 (1-sided α error 0.05; power 80%). In fit Cohort, 166 events were needed / 430 pts to detect a HR of 0.64 (2-sided α error 0.05; power 80%).

Results

Between 2017 and 2020, 707 patients were randomized, 6 withdrew consent. Unfit Cohort: 275 pts, median age 67 years, 61% OPC including 35% p16+. The number of events was reached in 2021, the current analysis is a long-term update. With a median follow-up of 47.7 months (IQR 39.4-56.0) and 200 PFS events, HR was 0.80 (95%CI 0.60-1.06); 4-year PFS rate was 33.7% (95%CI 26.2%-42.2%) in Exp vs 18.4% (95%CI 12.5%-26.1%) in SOC-cetux. Distant metastasis rate remained lower in Exp (subHR 0.24 (95%CI 0.11-0.49)). No significant difference in OS was seen between arms (HR 1.05 (95%CI 0.76-1.44). Fit Cohort: 426 pts, median age 59 years, 70% oropharyngeal cancer (OPC) including 49% p16+. With a median follow-up of 50.8 months (IQR 45.8-57.4) and 224 PFS events, PFS was significantly lower in Exp than in SOC-cisplatin: HR 1.40 (95%CI 1.12-1.75), p=0.012; 4-year PFS rate 42.3% (95%CI 35.7%-49.2%) in Exp vs 54.7% in SOC-cisplatin (95%CI 47.8%-61.4%). OS was also lower in Exp than in SOC-cisplatin (HR=1.45, 95%CI 1.12-1.87, p=0.017).

Conclusions

In cisplatin-unfit pts, a favorable effect of adding avelumab to cetuximab-RT was seen on PFS and distant metastases but not on OS. In cisplatin-fit pts, the SOC cisplatin-RT was superior to combination of cetuximab-avelumab-RT.

Clinical trial identification

NCT02999087.

Editorial acknowledgement

Legal entity responsible for the study

GORTEC.

Funding

GORTEC with a funding from Merck Serono. This research was financially supported by Merck Serono S.A.S, Lyon, France, an affiliate of Merck KGaA, as part of an alliance between Merck (CrossRef Funder ID: 10.13039/100009945) and Pfizer.

Disclosure

Y. Tao: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Merck, Seagen. X. Sun: Non-Financial Interests, Personal, Principal Investigator: Merck. Y. Pointreau: Financial Interests, Personal and Institutional, Invited Speaker: Merck; Non-Financial Interests, Personal, Principal Investigator: Merck. C. Borel: Financial Interests, Personal, Invited Speaker: MSD, Merck Serono, BMS, AstraZeneca; Financial Interests, Personal, Advisory Board: Merck Serono, AstraZeneca, MSD. F. Rolland: Financial Interests, Personal, Advisory Board: Pfizer, Eisai, MSD, Merck Serono; Financial Interests, Institutional, Coordinating PI: Exelixis; Financial Interests, Institutional, Local PI: BMS, Ipsen. F. Clatot: Financial Interests, Personal, Invited Speaker: Merck. C. Even: Financial Interests, Personal, Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory Board: F Star Therapeutics, Novartis, Elevar, Bicara, PDS Biotechnology, GSK, Merus; Financial Interests, Institutional, Local PI: BMS, AstraZeneca, ISA pharmaceutics, MSD, Debiopharma, Ayala, Gilead, GSK, Beigene, Takeda, Genmab, Seagen, Nykode; Financial Interests, Institutional, Coordinating PI: BMS, Novartis, Sanofi. E.B. Saada: Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: Merck Serono, MSD; Financial Interests, Coordinating PI: Novartis; Financial Interests, Institutional, Coordinating PI: Roche. J. Guigay: Financial Interests, Personal, Advisory Board: BMS, Hookipa, MSD, Merck, Nanobiotix, Roche. J. Bourhis: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Debiopharm, Merck, MSD, Nanobiotix, Roche. All other authors have declared no conflicts of interest.