Intergroup phase III trial of neo-adjuvant chemotherapy, followed by chemoradiation and surgery with and without cetuximab in locally advanced esophageal carcinoma: First results from the SAKK 75/08 trial

4019 Background: We compared chemoradiotherapy followed by surgery with the addition of neoadjuvant and adjuvant cetuximab (cetux) in patients with esophageal carcinoma. Methods: Pts with resectable esophageal cancer (T2N1-3;T3-4aNx) received two cycles of induction chemotherapy (docetaxel 75mg/m2, cisplatin 75mg/m2) followed by chemoradiation (45 Gy, docetaxel 20mg/m2 and cisplatin 25mg/m2 weekly) and surgery or the same treatment with addition of neoadjuvant cetux 250mg/m2 weekly and adjuvant cetux 500mg/m2 bi-weekly for three months. Primary endpoint was progression-free survival (PFS). After a median follow-up of 4y 166 of the planned 180 events occurred (plateau reached). Results: 300 pts were treated between 2010-13: 88% male, median age 61y, 63% adenocarcinoma, 85% cT3/4a, 90% cN+. 84% completed neoadjuvant therapy, 87% were operated (cetux: 89%, control: 86%), 67% started and 50% completed adjuvant cetux-therapy. The R0 resection rate was 95% in the cetux-arm and 97% in the control-arm, there were 10 and 14 treatment-related deaths and 9 and 4 postoperative in-hospital deaths, respectively. Major differences in adverse events (grade >2) with addition of cetux were higher rate of allergic reactions and hypomagnesemia, but lower rate of dysphagia (-15%) and esophagitis (-4%) during chemoradiation. Conclusions: The addition of cetuximab to a multimodal therapy showed a statistically significant reduction of loco-regional recurrences which led to a statistically non-significant, but clinically relevant improvement of PFS and OS. Clinical trial information: NCT01107639. [Table: see text]