Adjuvant Capecitabine and Oxaliplatin for Gastric Cancer: Results of the Phase 3 CLASSIC Trial

CHICAGO— Adjuvant capecitabine and oxaliplatin (XELOX) demonstrated superior efficacy when compared with observation alone following D2 gastrectomy for gastric cancer, according to study results presented at the American Society of Clinical Oncology's 2011 Annual Meeting.

Surgical resection is a recommended treatment for operable gastric cancer in general, despite high recurrence rates (40%–80%). Adjuvant chemotherapy aims to reduce recurrences; however, there is currently no universally accepted adjuvant regimen for gastric cancer. 

Yung-Jue Bang, MD, from Seoul National University College of Medicine, Seoul, Korea, and colleagues presented the CLASSIC trial, a randomized, open-label, multicenter, international study of XELOX (capecitabine 1000mg/m2 twice daily, Days 1–14, every 3 weeks and oxaliplatin 130mg/m2, Day 1, every 3 weeks for eight cycles) vs. observation following D2 gastrectomy. Eligible patients were chemotherapy- and radiotherapy-naive, with stage II (T2N1, T1N2, T3N0), IIIa (T3N1, T2N2, T4N0), or IIIb (T3N2) gastric cancer resected within 6 weeks prior to randomization.

The primary endpoint is 3-year disease-free survival (DFS). A sample size of 512 patients per arm was planned to observe the 385 DFS events required to provide 80% power at a 5% significance level for the hypothesized treatment effect (hazard ratio [HR] 0.75). The Independent Data Monitoring Committee recommended full evaluation and reporting of results following a positive pre-planned interim analysis at 266 events. 

The XELOX and observation arms (ITT populations of 520 and 515 patients, respectively) were well balanced for baseline characteristics. The median duration of follow-up was 34.4 (16–51) months. XELOX-related Grade 3/4 adverse events (AEs) occurred in 244/496 patients (49%) of the safety population. Neutropenia was the only AE observed in >10% of patients (21%, n=106/496). Serious XELOX-related Grade 3/4 AEs occurred in  (14%) patients. There were 62/496 (13%) and 80/476 (17%) deaths on study in the safety populations of XELOX and observation arms, respectively, mostly due to disease progression. Efficacy results in the ITT population are summarized below. See Table.

Dr. Bang et al conclude that the CLASSIC study demonstrates the superior efficacy of adjuvant XELOX vs. observation alone following D2 gastrectomy. Although OS data are still immature, there is a trend towards superiority of XELOX. The investigators state that these data support the use of adjuvant XELOX for gastric cancer.