Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial
Mené sur 788 patients atteints d'un adénocarcinome gastrique ou
Purpose: The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with postoperative chemoradiotherapy and perioperative chemotherapy. Intention-to-treat analysis in the CRITICS trial of postoperative chemotherapy (CT) or postoperative chemoradiotherapy (CRT did not show a survival difference. The current study reports on the per-protocol (PP) analysis of the CRITICS trial. Patients and methods: The CRITICS trial was a randomized controlled trial in which 788 patients with stage Ib–IVa resectable gastric or esophagogastric adenocarcinoma were included. Before start of preoperative chemotherapy, patients from the Netherlands, Sweden, and Denmark were randomly assigned to postoperative CT or CRT. For the current analysis, only patients who started their allocated postoperative treatment were included. Since it is uncertain that the two treatment arms are balanced in such PP analysis, adjusted proportional hazards regression analysis and inverse probability weighted (IPW) analysis were used to minimize the risk of selection bias and to estimate and compare overall and event-free survival. Results: Of the 788 patients, 478 started postoperative treatment according to protocol, 233 (59%) patients in the CT group and 245 (62%) patients in the CRT group. Patient and tumor characteristics between the groups before start of the postoperative treatment were not different. After a median follow-up of 6.7 years since the start of postoperative treatment, the 5-year overall survival was 57.9% (95% confidence interval (CI) 51.4%-64.3%) in the CT group versus 45.5% (95% CI 39.2%-51.8%) in the CRT group (adjusted hazard ratio CRT versus CT: 1.62 (1.24-2.12), p=0.0004). IPW analysis resulted in similar hazard ratios. Conclusion: After adjustment for all known confounding factors, the per-protocol analysis of patients who started the allocated postoperative treatment in the CRITICS trial showed that the chemotherapy group had a significant better 5-year overall survival than the chemoradiotherapy group. (NCT00407186)
Annals of Oncology 2020