Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced Head and Neck Cancer. A phase II-III trial
Mené sur 421 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade localement avancé (durée médiane de suivi : 44,8 mois), cet essai de phase II/III évalue, du point de vue de la survie globale, l'intérêt d'ajouter une chimiothérapie d'induction par docétaxel-cisplatine-5 fluorouracile à une chimioradiothérapie concomitante
Background : Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clincal trials. The goals of this phase II-III trial were to assess: 1) the overall survival (OS) of IC vs. no-induction (no-IC), 2) the Grade 3-4 in-field mucosal toxicity of CCRT vs. CET/RT. The present paper focuses on the analysis of efficacy. Methods : Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or 3 cycles of induction docetaxel/cisplatin/5fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC vs. no-IC (Arms B1+B2 vs. A1+A2) require 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level). Results : 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95%CI 0.56-0.97; p = 0.031). Complete Responses (p = 0.0028), Progression Free Survival (p = 0.013) and the Locoregional Control (p = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF. Conclusions : IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy.