Perioperative trastuzumab, capecitabine and oxaliplatin in patients with HER2-positive resectable gastric or gastro-oesophageal junction adenocarcinoma: NEOHX phase II trial.

Introduction: Perioperative chemotherapy improves overall survival (OS) and disease-free survival (DFS) compared with surgery alone in patients with resectable gastric adenocarcinoma (GA) or gastro-oesophageal junction adenocarcinoma (GEJA). The addition of trastuzumab to chemotherapy improves outcomes in patients with HER2-positive advanced gastric cancer (GC), and we aimed to explore its role in the perioperative setting.
Material and Methods: This Spanish, multicentre, open-label phase II trial evaluated the efficacy and toxicity of perioperative capecitabine, oxaliplatin and trastuzumab (XELOX-T) in patients with HER2-positive resectable GA or GEJA. The primary end-point was 18-months DFS; and secondary end-points included pathological complete response (pCR) rate, R0 resection rate, OS and toxicity (NCT01130337).
Results: Thirty-six patients were included. After three cycles of preoperative treatment, 14 patients (38% of the intention-to-treat population) had partial response and 18 (50%) had stable disease. Surgery was performed in 31 patients: 28 (90%) had R0 resection, three (9.6%) had a pCR and three (9.6%) died due to surgical complications. A total of 24 patients received post-operative XELOX-T, 22 of whom completed trastuzumab maintenance. Main grade III/IV toxicities included diarrhoea (33%), nausea and vomiting (8%). After a median follow-up of 24.1 months, 18-month DFS was 71% (95% confidence interval [CI], 53-83%); and an update after 102 months of follow-up showed a median OS of 79.9 months and a 60-month OS of 58% (95% CI, 40-73%).
Conclusions: These data suggest that perioperative XELOX-T in patients with HER2-positive GA and GEJA is feasible and active. Further investigation in randomised studies is warranted.
Competing Interests: Conflict of interest statement Paula Jimenez-Fonseca declares travel grants from Ipsen and consulting/advisory role for Roche, Celgene, Bristol, Mylan, Rovi, LeoPharma, all outside of the scope of this work. Maria Alsina declares disclosures in terms of scientific consultancy from Bristol Myers Squibb, Lilly, Merck Sharp and Dohme, and Servier; honoraria from Amgen, Bristol Myers Squibb, Lilly, Merck Sharp and Dohme, Roche, and Servier; and travel expenses (partial coverage) from Amgen, Lilly, and Roche. Enrique Aranda disclosures consultant or advisory role for Roche, Merck, Angem, Bayer and Sanofi. Carlos López disclosures Honoraria for Roche, Merck, Sanofi, Novartis, Pfizer, Eisai, Ipsen, Bayer, AstraZeneca, and Servier; Consulting or Advisory Role for Amgen, Roche, Sanofi, Merck, Servier, Pfizer, Ipsen, Bayer, Eisai; research funding from Amgen, Roche, Merck, Merck Sharp & Dohme, AstraZeneca, Sanofi, Bayer, Ipsen, Eisai, Celgene Travel, Accommodations, Expenses Roche, Pfizer, Merck, Servier, Amgen, Ipsen Fernando Rivera disclosures consultant or advisory role for Roche, Merck-Serono, Amgen, MSD, BMS, Lilly, Celgene, Sanofi-Aventis, Servier, Astra-Zeneca, and Bayer; research Funding from Roche, Merck-Serono, Amgen, MSD, Lilly, Celgene, Sanofi-Aventis, Bayer, Servier; speaker roles for Roche, Merck-Serono, Amgen, MSD, BMS, Lilly, Celgene, Sanofi-Aventis, Servier, and Bayer; and grant support from Amgen. The rest of the authors declare no conflicts of interest.
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