Background: CetRT has not been compared with CRT after ICT in phase III. Objective: To compare the impact on overall survival of CRT vs. CetRT after ICT in a Phase III randomized controlled clinical trial with a non-inferiority design of CetRT compared to CRT. Response Rate (RR), loco-regional control (LRC) and toxicity in both arms were considered secondary objectives. Methods: Pts with LAUHNC, ECOG 0-1, 18-72 years old, measurable disease, and with adequate renal and liver function, received standard DCF with G-CSF. After at least 2 cycles (range 2-3), pts with objective response or stable disease were randomized (stratified by tumor location, 1:1) between cisplatin 100 mg/m2 days 1, 22, 43) plus radiotherapy (dose 68-72 Gy, in 35 fractions) (arm A) or cetuximab (400mg d1, 250mg/m2 weekly concurrent with RT) plus the same radiotherapy scheme (arm B). Non-inferiority will be assumed if the upper limit of the one-sided 95% CI of the hazard ratio for OS (CetRT/CRT) is below 1.3. Analyses were done by intention to treat. Results: 530 pts were enrolled and 407 randomized (arm A: 205; arm B: 202). Median age 56 years , 89% male, ECOG 1: 70%, oropharynx and hypopharynx: 64%, T3/T4: 81%, N2/N3: 76%. During ICT the major causes of discontinuation were progressive disease or toxicity (24%). Median number of DCF cycles was 3 (range 0-3). RR during ICT was 71%. Toxicity G3/4 was observed in 40% of pts. After randomization the median number of cisplatin cycles was 3 (range 1-3), median number of cetuximab cycles was 8 (range 1-15) and median dose of radiotherapy was 70Gy (range 62-72 Gy). After CRT and CetRT, RRs were 72% and 78%, respectively. Toxicity (G3/4 RTOG) during CRT and CetRT were 36% and 32%, respectively. With a median follow up of 36 months LRC were 56% in arm A vs. 52% in arm B ( hazard ratio (HR), 1.13; 95% CI , 0.84 to 1.51 ) p value = 0.4 Conclusions: This is the first randomized Phase III trial that compare CRT vs. CetRT after ICT in pts with LAUHNC. The RR, toxicity and LRC were similar in both arms. With a long follow up, data of survival will be present in the meeting. Clinical trial information: NCT00716391