Perioperative Cetuximab with Cisplatin and 5-Fluorouracil in Esogastric Adenocarcinoma: A Phase II Study

SIMPLE SUMMARY: The treatment of resectable gastric and gastroesophageal junction adenocarcinomas is enhanced by a strategy of perioperative chemotherapy (CT) when compared with surgery alone. But, there is still a need for new approaches to further improve outcomes in patients treated with perioperative CT. Cetuximab, a human–murine chimeric monoclonal antibody binds with a high affinity to the EGFR binding site, and has shown activity against a variety of tumors, including G/GEJ adenocarcinomas. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin for the treatment of gastric and esophageal adenocarcinoma. The results of this phase two study showed safety but lack of efficacy regarding objective tumor response and absence of major toxicity. ABSTRACT: Purpose: While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin. Patients and Methods: Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively). Results: From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 [95% CI: 16.4–39.4] and 40.3 months [95% CI: 27.5–NA], respectively. Conclusion: Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086).