Adjuvant Capecitabine and Oxaliplatin for Gastric Cancer After D2 Gastrectomy (CLASSIC): A Phase 3 Open-Label, Randomised Controlled Trial
Bang YJ, Kim YW, Yang HK, et al
Lancet. 2012;379:315-321
Study Summary
The benefit of adjuvant chemotherapy after D2 resection for gastric cancer (the preferred procedure in Asian countries) is not well studied. The CLASSIC study was an open-label, parallel-group, phase 3, randomized controlled trial that was conducted in 37 centers in South Korea, China, and Taiwan. Patients with stage II to IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned to receive eight 3-week cycles of oral capecitabine (1000 mg/m twice daily on days 1-14 of each cycle) plus intravenous oxaliplatin (130 mg/m on day 1 of each cycle) for 6 months, or surgery only. The primary endpoint was 3-year disease-free survival (DFS). The study population comprised 1035 patients.
As reported, the 3-year DFS was 74% (95% confidence interval [CI], 69-79) in the chemotherapy plus surgery group and 59% (95% CI, 53-64) in the surgery-only group (hazard ratio 0.56, 95% CI, 0.44-0.72; P < .0001). The 3-year overall survival (OS) was also improved (83% vs 78%, P = .049) in the combined therapy group, although follow-up is still ongoing and these are preliminary OS results.
In subgroup analysis, benefit for adjuvant chemotherapy was present for all stages as well as for subgroups of patients with N1 or N2 disease, but not for patients with N0 disease. Grade 3 or 4 adverse events were reported in 56% of the chemotherapy-plus-surgery group vs 6% in the surgery-only group. The most common adverse events were nausea, neutropenia, and decreased appetite.
Viewpoint
The appropriate adjuvant regimen for gastric cancer post-resection remains controversial. In Asia, the standard of care for resectable gastric cancer is to conduct a D2 resection followed by oral fluoropyrimidine S-1, on the basis of results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) trial, which showed an OS benefit for adjuvant S-1. In Europe and North America, D1 resection is more common, and results from the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial and the Intergroup study have led to variation in adjuvant treatment, including triplet regimens such as ECX (epirubicin, cisplatin, and capecitabine) or postoperative 5-fluorouracil with radiation therapy.
This study confirms that adjuvant chemotherapy improves outcomes in gastric cancer, even for those patients treated with a more extensive surgical procedure. The study also supports the use of oxaliplatin- and capecitabine-based regimens. However, the applicability of findings to North American patients is unclear given the known differences in natural history of gastric cancer in Asia vs North America. Adherence to the regimen was also an issue in this study, with 10% of patients withdrawing because of adverse events. However, in patients for whom an epirubicin-based regimen is being considered but is contraindicated, capecitabine may be a viable alternative adjuvant regimen.
Abstract