OC-006: Concomitant treatment (CRT or cetuximab/RT) with or without induction TPF in Locally Advanced head and neck

Purpose/Objective: Patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progress after first-line platinum-based therapy have a dismal prognosis and limited efficacious treatment options. Afatinib, an irreversible ErbB family blocker, showed anti-tumour activity in a phase II trial in this setting (Seiwert et al. Ann Oncol 2014). LUX-Head & Neck 1, a global, openlabel, randomised phase III trial, evaluated second-line afatinib vs methotrexate (MTX) in patients with R/M HNSCC who progressed on/after platinum-based therapy (NCT01345682). Materials and Methods: Patients were randomised 2:1 to 40 mg/day oral afatinib (n=322) or 40 mg/m/week intravenous MTX (n=161), stratified by Eastern Cooperative Oncology Group performance status (0/1) and prior use of anti-EGFR antibody therapy (Yes/No) in the R/M setting. The primary endpoint was progression-free survival (PFS) by independent central review; overall survival (OS) was the key secondary endpoint. Other endpoints included objective response rate (ORR), patient-reported outcomes (PROs), tumour shrinkage, and adverse events (AEs). Disease control rate (DCR) was also assessed. Results: Patient baseline characteristics were well balanced between treatment groups (Table). Afatinib significantly improved the primary endpoint of PFS vs MTX by independent central review (median 2.6 vs 1.7 months; HR=0.80 [95% CI 0.65–0.98; p=0.03]; Figure); similar results were observed by investigator assessment. A trend towards improved PFS with afatinib was observed in a subgroup of patients aged ≥65 years (HR=0.68 [95% CI 0.45–1.03]). OS was not significantly improved with afatinib vs MTX (median 6.8 vs 6.0 months; HR=0.96 [0.77–1.19]). DCR was higher with afatinib vs MTX (49.1% vs 38.5%; p=0.04); ORR was 10.2% vs 5.6%, respectively (p=0.10). Tumour shrinkage was observed in 34.8% of afatinib-treated patients vs 22.4% of MTX-treated patients. Afatinib significantly delayed deterioration of global health status, pain and swallowing (all p≤0.03); significantly less pain over time was observed in afatinib-treated patients (p=0.03). Median duration of treatment was 83 days (range, 2–546) with afatinib and 43 days (range, 1–442) with MTX. The most frequent grade 3/4 treatment-related AEs were rash/acne (9.7%) and diarrhoea (9.4%) with afatinib, and stomatitis (8.1%) and neutropenia (6.9%) with MTX. Fewer treatment-related AEs led to dose reductions (32.2% vs 41.9%), drug discontinuations (7.2% vs 16.3%) or fatal outcome (2 [0.6%] vs 5 [3.1%]) in afatinib-treated patients. Conclusions: In this phase III trial in patients with R/M HNSCC after failure of platinum-based therapy, second-line afatinib significantly improved the primary endpoint of PFS vs MTX, with a manageable safety profile. A significant delay in deterioration of PROs and less pain over time was also observed with afatinib compared to MTX. OC-006 Concomitant treatment (CRT or cetuximab/RT) with or without induction TPF in Locally Advanced head and neck Cancer M.G. Ghi, A. Paccagnella, D. Ferrari, P. Foa, M. Cossu Rocca, E. Verri, F. Morelli, G. Azzarello, C. D'Ambrosio, C. Casanova, M. Guaraldi, E. Massa, C. Rossetto, A. Bonetti, S. Siena, A. Frattegiani, H. Koussis, G. Pieri, A. Gava, I. Floriani, For the GSTTC Italian Study Group Ospedale SS Giovanni e Paolo, Medical Oncology, Venezia, Italy San Paolo Hospital, Medical Oncology Unit, Milano, Italy Medical Oncology Unit of Urogenital and Head and Neck Tumors, European Institute of Oncology, Milano, Italy IRCCS Casa Sollievo della Sofferenza, Medical Oncology, San Giovanni Rotondo, Italy Azienda ULSS 13, Internal Medical Sciences, Mirano, Italy University Hospital, Oncology, Modena, Italy Azienda USL, Medical Oncology, Ravenna, Italy Policlinico Sant'Orsola-Malpighi, Medical Oncology, Bologna, Italy Azienda Ospedaliero Universitaria, Internal Medical Science, Cagliari, Italy University Hospital, Oncology, Udine, Italy Mater Salutis Hospital-AULSS 21 della Regione Veneto, Legnago, Italy Niguarda Ca' Granda Hospital, Milano, Italy Azienda Ospedaliera, Raditation Therapy, Perugia, Italy Istituto Oncologico Veneto IRCCS, Padova, Italy Ospedali Riuniti di Trieste, Oncology, Trieste, Italy Ospedale Ca Foncello, Radiation Therapy Department, Treviso, Italy Laboratorio Trials Clinici, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy