ERCC1 is a prognostic biomarker in locally advanced head and neck cancer: results from a randomised, phase II trial
Menée à partir d'échantillons tumoraux prélevés sur 90 patients atteints d'un carcinome épidermoïde de la tête et du cou et inclus dans un essai randomisé de phase II évaluant une chimioradiothérapie par cisplatine avec et sans erlotinib, cette étude montre une association entre l'expression de la protéine ERCC1 et la survie sans progression
Background : Cisplatin-radiotherapy is a preferred standard for locally advanced, head and neck squamous cell carcinoma (HNSCC). However, the cisplatin-attributable survival benefit is small and toxicity substantial. A biomarker of cisplatin resistance could guide treatment selection and spare morbidity. The ERCC1-XPF nuclease is critical to DNA repair pathways resolving cisplatin-induced lesions.
Methods : In a phase II trial, patients with untreated Stage III-IVb HNSCC were randomised to cisplatin-radiotherapy with/without erlotinib. Archived primary tumours were available from 90 of 204 patients for this planned substudy. Semi-quantitative ERCC1 protein expression (H-score) was determined using the FL297, 4F9, and 8F1 antibodies. The primary analysis evaluated the relationship between continuous ERCC1 protein expression and progression-free survival (PFS). Secondary analyses included two pre-specified ERCC1 cutpoints and performance in HPV-associated disease.
Results : Higher ERCC1 expression was associated with inferior PFS, as measured by the specific antibodies FL297 (HR=2.5, 95% CI=1.1–5.9, P=0.03) and 4F9 (HR=3.0, 95% CI=1.2–7.8, P=0.02). Patients with increased vs decreased/normal ERCC1 expression experienced inferior PFS (HR=4.8 for FL297, P=0.003; HR=5.5 for 4F9, P=0.007). This threshold remained prognostic in HPV-associated disease.
Conclusion : ERCC1-XPF protein expression by the specific FL297 and 4F9 antibodies is prognostic in patients undergoing definitive cisplatin-radiotherapy for HNSCC, irrespective of HPV status.
British Journal of Cancer , résumé, 2012