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Perioperative chemotherapy (CT) and postoperative chemoradiotherapy (CRT) are standard treatment options for locally advanced resectable gastric cancer. From the CRITICS and other studies it is known that these multimodality regimens are associated with poor patient tolerability, especially in the postoperative phase. The CRITICS-II trial was designed to identify the optimal preoperative strategy in resectable gastric cancer by comparing 3 arms. A preplanned interim analysis (IA) was performed and reviewed by the Independent Data Safety Monitoring Committee to determine any imbalances between the 3 arms that could necessitate the discontinuation of any of the treatment arms. 

CRITICS-II is a randomised phase II trial evaluating 3 experimental preoperative treatment arms independently according to the “pick the winner” principle. Patients are randomised to: 4 cycles of docetaxel/oxaliplatin/capecitabine (DOC); 2 cycles of DOC followed by CRT (45 Gy with weekly carboplatin/docetaxel; DOC-CRT); or CRT only. Primary endpoint is event-free survival at 1 year; secondary endpoints are time to event, time to recurrence, R0 resection rate, pCR rate, complications, toxicity and overall survival. Here, we report the results of the IA with a focus on baseline characteristics, patient compliance, surgical and pathology details, complications and toxicity.

At a median follow-up of 14 months, 119 randomised patients were eligible for this IA. No significant imbalances were found in baseline characteristics. Completion of preoperative treatment for the total group was 89%. Main reasons for not completing preoperative treatment were toxicity (n=7), death (n=2), disease progression (n=1) and patient’s refusal (n=1). Surgery was performed in 92% of patients. Reasons for not proceeding to surgery were disease progression (n=4), toxicity (n=3) and patient’s refusal (n=1). Surgery was with curative intent in 99% of patients, and involved a total gastrectomy in 51% and a D2 lymph node dissection in 93%. In-hospital mortality was 6%. Surgical complications occurred in 18% and consisted of anastomotic leakage (n=7), bleeding (n=2), fistula (n=1), ileus (n=1), necrosis (n=1) and other (n=5). R0 resection was obtained in 95% and the median number of lymph nodes was 22. The percentage of patients who completed treatment according to protocol was 80% for the total group. Main reasons for not completing were disease progression (6%), toxicity (5%), death (5%) and patient’s refusal (1%). Maximum grade 3-5 any toxicity was 61%; grade 5 toxicity was 8%. Cause of death was of infectious (n=5) or pulmonary (n=4) origin.

Interim results from the CRITICS-II trial showed a high patient compliance rate. Treatment-related toxicity and surgical morbidity were significant, but in line with previous studies. No major imbalances were detected between the 3 preoperative treatment arms; accrual continues as planned up to a total of 207 patients.