Afatinib maintenance therapy following post-operative radiochemotherapy in head and neck squamous cell carconoma: results from the phase III randomized double-blind placebo-controlled study BIB2992ORL (GORTEC 2010-02)
Mené en France sur 167 patients atteints d'un carcinome épidermoïde de la tête et du cou réséqué, cet essai randomisé multicentrique de phase III évalue l'efficacité, du point de vue de la survie sans maladie, d'un traitement d'entretien d'1 an par afatinib chez les patients ayant reçu une radiochimiothérapie postopératoire avec cisplatine
Objective: We investigated the efficacy and safety of afatinib maintenance therapy in patients with head and neck squamous cell carcinoma (HNSCC) with macroscopically complete resection and adjuvant radiochemotherapy (RCT). Methods: This French multicentric randomized phase III double-blind placebo-controlled study included adult patients with ECOG-PS≤2, normal hematological, hepatic and renal functions, and non metastatic, histologically confirmed HNSCC of the oral cavity, oropharynx, larynx or hypopharynx, with macroscopically complete resection and adjuvant RCT (≥2 cycles of cisplatin 100 mg/m2 J1, J22, J43 and 66Gy (2Gy/fraction, 5 fractions/week, conventional or intensity modulated radiotherapy ≥60Gy). Randomized patients were planned to receive either afatinib (afa arm) or placebo (control arm (C)) as maintenance therapy for one year. Primary endpoint was disease free survival (DFS). A 15% improvement in DFS was expected at 2 years with afatinib (from 55 to 70%). Results: Among the 167 patients with resected HNSCC included in 19 cancer centers and hospitals from Dec 2011, 134 patients were randomized to receive one-year maintenance afatinib or placebo (afa:67; C:67). Benefit/risk ratio was below assumptions and independent advisory committee recommended to stop the study in Feb 2017, the sponsor decided premature study discontinuation, with a 2-year follow-up for the last randomized patient. 2y-DFS was 61% (95%CI 0.48-0.72) in the afatinib group and 64% (95%CI 0.51-0.74) in the placebo group (HR 1.12, 95%CI 0.70-1.80). Conclusion: Maintenance therapy with afatinib compared with placebo following post-operative RCT in patients with HNSCC did not significantly improve 2y-DFS. and should not be recommended in this setting outside clinical trials. ClinicalTrials.gov identifier NCT01427478