857O - MACH-EGFR: Individual patient data (IPD) meta-analysis of anti-EGFR monoclonal antibodies (Ab) in patients (pts) with locally advanced (LA) squamous cell carcinomas of head and neck (SCCHN)

Background

The epidermal growth factor receptor (EGFR) pathway is involved in HNSCC progression. Multiple trials have studied anti-EGFR Ab combined to loco-regional treatment (LRT) in LA HNSCC with conflicting results. We report the results of the IPD meta-analysis.

Methods

Randomized trials in pts with LA HNSCC comparing curative LRT +/- chemotherapy (CT) vs same treatment + anti-EGFR Ab (comparison 1) or LRT + CT vs LRT + anti-EGFR Ab (comparison 2) and that completed enrolment before 2019 were eligible. IPD were collected and combined using fixed-effect models. Overall survival (OS) was the main endpoint. Data on locoregional/distant progressions and toxicity were also collected.

Results

The table presents trials/pts’ characteristics. In comparison 1, the addition of anti-EGFR Ab did not significantly increase OS with a pooled HR of 0.92 (95%CI 0.82;1.03), p=0.13. Differences were seen according to type of Ab: HR (95%CI) was 0.85 (0.73;1.00) for cetuximab, 0.82 (0.66;1.01) for nimotuzumab, 1.59 (0.89;2.85) for panitumumab, 1.21 (0.92;1.58) for zalutumumab. Younger pts (<50 years) benefited more from addition of anti-EGFR Ab. Interaction with p16 in oropharyngeal cancer (OPC) will be presented at the meeting. In comparison 2, anti-EGFR Ab was significantly associated with decreased OS compared to CT, with a pooled HR of 1.21 (95%CI 1.05;1.39), p=0.007, corresponding to an absolute OS decrease of 4.5% at 3 years. Administration of induction CT (ICT) could influence HR: 1.04 (0.84;1.29) in case of ICT vs 1.36 (1.13;1.63) in absence of ICT (p=0.07). Benefit of CT over anti-EGFR Ab on OS was higher in females and in OPC than in other sites. Table: 857O

Conclusions

There was no survival benefit with the addition of Ab to LRT for either comparison. Importantly, replacing CT with anti-EGFR Ab, as systemic treatment added to LRT, results in inferior survival.

Clinical trial identification

PROSPERO: CRD42017056939.

Editorial acknowledgement

Legal entity responsible for the study

MACH-EGFR collaborative group.

Funding

French Ministry of Health.

Disclosure

P. Blanchard: Financial Interests, Institutional, Invited Speaker: Ipsen, Sanofi Aventis, Janssen, MSD; Financial Interests, Personal, Invited Speaker, advisory board and speaker at conferences: Bayer; Financial Interests, Institutional, Advisory Board: Becton Dickinson; Financial Interests, Institutional, Full or part-time Employment, Editor in Chief - Clinical and Translational Radiation Oncology: ESTRO. K. Prabhash: Financial Interests, Institutional, Research Funding: Roche, Alkem India, AstraZeneca. M.G. Ghi: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, BMS, Merck Serono; Financial Interests, Personal, Other, travel to meetings: MSD, BMS, Merck Serono. H. Mehanna: Financial Interests, Personal and Institutional, Funding: AstraZeneca; Financial Interests, Personal, Other, travel to meetings: Merck Serono, MSD; Financial Interests, Personal, Advisory Board: Seagen, Nanobiotix, Merck Serono. R. Mesia Nin: Financial Interests, Personal, Advisory Board: Merck, MSD, Bayer, Seattle Genetics, Nanobiotix, Boehringer, Segean; Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS; Non-Financial Interests, Principal Investigator, Clinical Trial PI: BMS; Non-Financial Interests, Principal Investigator, Observational trial PI: Merck. Y. Pointreau: Financial Interests, Personal, Invited Speaker: Merck Serono. A. Auperin: Financial Interests, Institutional, Funding: MSD. All other authors have declared no conflicts of interest.