Background: Standard of care for SCAC has remained unchanged over the past 4 decades. More than 80% of these tumors overexpress the EGFR receptor and <5% present KRAS mutations (Van Damme, BMC 2010). We therefore initiated a multicenter phase II study (NCT01285778) to assess the efficacy and tolerability of adding the EGFR inhibitor panitumumab to the standard M/5FU/RT regimen in patients with non-metastatic SCAC. Methods: Patients received P (6 mg/kg on day 1, every 2 weeks for 8 weeks), M (10mg/m2 q28 days x2) and 5-FU (1000mg/m2/day IV infusion days 1-4 q 28 days x 2) concurrently with RT 45 Gy (1,8 Gy per fraction) to the primary tumor, mesorectal, iliac and inguinal nodes, followed by a boost of 10-15 Gy to the primary tumor and affected lymph nodes. The trial was designed to include 58 pts with stage >T2N0 to have 80% power to detect an increment of 3y-DFS rate from 50% (Ajani, JAMA 2008) to 70%. Results: Between 1/2011 and 11/2013, 58 pts were accrued. To date, results of 36 patients are available (56% female, median age 54 years, VIH positive 6%, ECOG PS: 0 (44%)/1 (53%)/2 (3%), stage I (3%)/II (25%)/IIIA (19%)/IIIB (50%). Thirty-three (92%) patients developed G3/4 adverse events (Table 1). There were no toxic deaths. At 8 weeks, 56% pts experienced CR; 36% persistent but not progressive disease and 8% disease progression. At 24 weeks 55% had CR, 6% persistent but not progressive disease; 19% disease progression, and 20% had not been evaluated. Conclusions: The addition of P to M/5-FU/RT is a tolerable regimen with a good compliance and an acceptable safety profile. Full data of toxicity and post-treatment CR rate will be reported at ASCO Meeting. Clinical trial information: NCT01285778.