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Abstract
Purpose To investigate the effect of adding concurrent chemotherapy (CT) to cetuximab plus radiotherapy (RT; CT-cetux-RT) compared with cetuximab plus RT (cetux-RT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Patients and Methods In this phase III randomized trial, patients with N0-2b, nonoperated, stage III or IV (nonmetastatic) LA-SCCHN were enrolled. Patients received once-daily RT up to 70 Gy with weekly cetuximab or with weekly cetuximab and concurrent carboplatin and fluorouracil (three cycles). To detect a hazard ratio (HR) of 0.64 for progression-free survival (PFS) with 85% power at a two-sided significance level of P = .05, 203 patients needed to be included in each arm. Results Four hundred six patients were randomly assigned to either CT-cetux-RT or cetux-RT. Patient and tumor characteristics were well balanced between arms, including p16 status. With a median follow-up of 4.4 years, the HR for PFS favored the CT-cetux-RT arm (HR, 0.73; 95% CI, 0.57 to 0.94; P = .015), with 3-year PFS rates of 52.3% and 40.5% and median PFS times of 37.9 and 22.4 months in the CT-cetux-RT and cetux-RT arms, respectively. The HR for locoregional control was 0.54 (95% CI, 0.38 to 0.76; P < .001) in favor of CT-cetux-RT. These benefits were observed regardless of p16 status for oropharynx carcinomas. Overall survival (HR, 0.80; P = .11) and distant metastases rates (HR, 1.19; P = .50) were not significantly different between the two arms. The CT-cetux-RT arm, compared with cetux-RT, had a higher incidence of grade 3 or 4 mucositis (73% v 61%, respectively; P = .014) and of hospitalizations for toxicity (42% v 22%, respectively; P < .001). Conclusion The addition of concurrent carboplatin and fluorouracil to cetux-RT improved PFS and locoregional control, with a nonsignificant gain in survival. To our knowledge, this is the first evidence of a clinical benefit for treatment intensification using cetux-RT as a backbone in LA-SCCHN.

Author information

Tao Y1, Auperin A1, Sire C1, Martin L1, Khoury C1, Maingon P1, Bardet E1, Kaminsky MC1, Lapeyre M1, Chatellier T1, Alfonsi M1, Pointreau Y1, Jadaud E1, Géry B1, Zawadi A1, Tourani JM1, Laguerre B1, Coutte A1, Racadot S1, Hasbini A1, Malaurie E1, Borel C1, Meert N1, Cornely A1, Ollivier N1, Casiraghi O1, Sun XS1, Bourhis J1.
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Yungan Tao, Anne Auperin, Alexandre Cornely, Nathalie Ollivier, Odile Casiraghi, and Jean Bourhis, Gustave-Roussy Institute, Villejuif; Christian Sire, Centre Hospitalier de Lorient, Lorient; Laurent Martin, Centre Guillaume le Conquérant, Le Havre; Cedric Khoury, Centre Hospitalier de Toulon, Toulon; Philippe Maingon, Centre Georges-François Leclerc, Dijon; Etienne Bardet, Centre René Gauducheau, Nantes; Marie-Christine Kaminsky, Centre Alexis Vautrin, Nancy; Michel Lapeyre, Centre Jean Perrin, Clermont; Thierry Chatellier, Clinique Mutualiste, Saint Nazaire; Marc Alfonsi, Clinique Sainte Catherine, Avignon; Yoann Pointreau, Centre Jean Bernard, Le Mans; Yoann Pointreau, Centre Hospitalier Universitaire (CHU) de Tours, Tours; Eric Jadaud, Centre Paul Papin, Angers; Bernard Géry, Centre François Baclesse, Caen; Ayman Zawadi, Centre Hospitalier de La Roche-sur-Yon, La Roche-sur-Yon; Jean-Marc Tourani, CHU, Poitiers; Brigitte Laguerre, Centre Eugène Marquis, Rennes; Alexandre Coutte, CHU, Amiens; Séverine Racadot, Centre Léon Bérard, Lyon; Ali Hasbini, Clinique Armoricaine, Saint-Brieuc; Emanuelle Malaurie, Centre Hospitalier Intercommunal de Créteil, Créteil; Christian Borel, Centre Paul Strauss, Strasbourg; Xu Shan Sun, Hopital Nord Franche-Comté de Montbéliard, Montbéliard; Xu Shan Sun, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; Nicolas Meert, Centre Hospitalier de Charleroi, Charleroi, Belgium; and Jean Bourhis, Centre Hospitalier Universitaire Vaudois Lausanne, Lausanne, Switzerland.