| General information |
| Database: | DB00390 |
| Objective: | Cisplatinradiotherapy is a preferred standard for locally advanced, head and neck squamous cell carcinoma (HNSCC). however, the cisplatinattributable survival benefit is small and toxicity substantial. A biomarker of cisplatin resistance could guide treatment selection and spare morbidity. The ERCC1XPF nuclease is critical to DNA repair pathways resolving cisplatininduced lesions. |
| Authors: | Bauman JE, et al |
| Title: | ERCC1 is a prognostic biomarker in locally advanced head and neck cancer: results from a randomised, phase II trial. |
| Journal: | Br J Cancer. |
| Year: | 2013 |
| PMID: | 24064970 |
| Trial Design |
| Clinical Trial Id: | NCT00410826 |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | cisplatinradiotherapy with/without erlotinib |
| Study Type: | analysis of a randomised, phase II trial |
| Key Patients Feature: | untreated Stage IIIIVb HNSCC |
| Biomarker: | Semiquantitative ERCC1 protein expression (Hscore) |
| Biomark Analysis: | Higher ERCC1 expression was associated with inferior PFS, as measured by the specific antibodies FL297 (HR=2.5, 95% CI=1.15.9, P=0.03) and 4F9 (HR=3.0, 95% CI=1.27.8, 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 HPVassociated disease. |
| Control Group Info: | cisplatinradiotherapy with/without erlotinib. |
| Treatment Info: | patients were randomised to cisplatinradiotherapy with/without erlotinib. Archived primary tumours were available from 90 of 204 patients for this planned substudy. Semiquantitative ERCC1 protein expression (Hscore) was determined using the FL297, 4F9, and 8F1 antibodies. |
| Primary End Point: | the relationship between continuous ERCC1 protein expression and progression free survival (PFS). |
| Secondary End Point: | two prespecified ERCC1 cutpoints and performance in HPVassociated disease. |
| Patients Number: | 90 of 204 patients for this planned substudy. |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | CRR according to standardised protocol criteria was 40% vs 52% on the standard vs experimental arm (P=0.08). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | ERCC1XPF protein expression by the specific FL297 and 4F9 antibodies is prognostic in patients undergoing definitive cisplatinradiotherapy for HNSCC, irrespective of HPV status. |