S2963
Late-Breaking
ESTRO 2026
16 Medical Oncology, Center of Molecular Immunology, Havana, Cuba Purpose/Objective: The epidermal growth factor receptor (EGFR) pathway is involved in head & neck squamous cell cancer (HNSCC) progression. Multiple trials have studied anti- EGFR antibodies (Ab) combined with loco-regional treatment (LRT) in loco-regionally advanced (LA) HNSCC with conflicting results. We presented the initial results of this meta-analysis at ESMO 2023 and report now the final results of the MACH-EGFR meta- analysis, after the inclusion of two additional trials (1049 additional patients, data received early 2026). Material/Methods: Randomized trials in pts with LA HNSCC comparing curative LRT (surgery or radiation) +/- chemotherapy (CT) vs the same treatment + anti-EGFR Ab. Individual patient data were collected and combined using fi xed- effect models. Overall survival (OS) was the main endpoint. Data on locoregional/distant progressions and toxicity were also collected. Results: Data from 11 trials (4146 pts) were collected (table). The addition of anti-EGFR Ab showed a near significant increased OS with a pooled HR of 0.91 (95%CI 0.82;1.00), p=0.054). There was a significant interaction (p=0.024) between OS effect and type of Ab: HR (95%CI) was 0.86 (0.75;0.99) for cetuximab (Cetux), 0.83 (0.69;0.99) for nimotuzumab (NTZab), 1.59 (0.89;2.85) for panitumumab, 1.21 (0.92;1.58) for zalutumumab. Similar findings were observed for progression-free survival (PFS) with a benefit observed only in Cetux/NTZab trials.When restricting the analysis to Cetux/NTZab trials, OS and PFS were significantly improved (HR 0.85 (0.76;0.95) and 0.87 (0.79;0.97) respectively), and cancer deaths were significantly reduced (HR 0.83 (0.74;0.94)). The subdistribution-HR of distant progressions and locoregional progressions were 0.84 (0.67;1.05) and 0.90 (0.79;1.03) respectively. Subgroup analyses on OS suggested that addition of anti-EGFR-Ab could be more efficacious in younger pts. In trials that included pts with oropharyngeal cancer (OPC) and for whom p16 status was known, a significant treatment-by-p16 interaction was observed on OS and PFS: anti-EGFR-Ab was associated with improved outcome in pts with p16-negative OPC, while no benefit, even a potential harm, was observed in pts with p16-positive OPC. However, p16 status was available for only 45% of pts with OPC.A multivariate Cox model stratified by trial showed that the factors significantly associated with improved OS/PFS were: use of anti-EGFR-Ab, female gender, younger age, better performance status, p16 positivity, oropharyngeal/laryngeal subsites, and earlier AJCC/UICC stages.
Conclusion: This updated meta-analysis showed a borderline survival benefit with the addition of EGFR-Ab to LRT. However this improvement was seen only with Cetux/NTZab. Subgroup analyses suggest an interaction with p16 status.PROSPERO: CRD42017056939 Keywords: Head and neck cancer; EGFR; meta- analysis
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