Final Results of a Randomized Phase II Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiotherapy for Locoregionally Advanced Head and Neck Cancer
Mené sur 110 patients atteints d'un cancer épidermoïde de la tête et du cou de stade loco-régionalement avancé (durée médiane de suivi : 72 mois), cet essai de phase II évalue, du point de vue de la tolérabilité, de la survie sans progression et de la survie globale à 2 et 5 ans, l'intérêt d'ajouter le cétuximab à une chimiothérapie d'induction et à un traitement combinant chimiothérapie et radiothérapie accélérée ou hyperfractionnée
Purpose : The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase II randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiotherapy. Methods and Materials : Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-FU, hydroxyurea, and 1.5 Gy twice-daily radiotherapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiotherapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared to historical control achieved if either arm had 2-year PFS ≥70%. Results : 110 patients were randomly assigned to either Cetux-FHX (N = 57) or Cetux-PX (N = 53). Overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). 2-year PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than historical control (P < 0.001). 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With median follow-up of 72 months, there were no significant differences in PFS (P = 0.35) or OS (P = 0.15) between treatment arms. Late outcomes for the entire cohort include 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. 5-year PFS and OS were 84.4% and 91.3%, respectively, among HPV-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions : The addition of cetuximab to IC and chemoradiotherapy was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum based chemoradiotherapy.