Adjuvant treatment with capecitabine and oxaliplatin extended survival compared with observation among patients with stage II to stage IIIb gastric cancer who underwent curative D2 gastrectomy, according to long-term follow-up of a randomized phase 3 trial.
The multicenter, open-label CLASSIC trial included 1,035 chemotherapy- and radiotherapy-naive patients with stage II, IIIa or IIIb gastric cancer who underwent curative D2 gastrectomy.
Researchers randomly assigned 520 patients to undergo adjuvant therapy with capecitabine 1,000mg/m2 plus oxaliplatin 130mg/m2. The other 515 patients underwent observation alone. DFS served as the primary endpoint.
The planned interim analysis, performed with a median follow-up of 34 months, showed the adjuvant regimen significantly improved DFS compared with observation.
In the current analysis, Sung Hoon Noh, MD, of the department of surgery at Yonsei University College of Medicine in South Korea, and colleagues reported 5-year follow-up data. Median follow-up in the intention-to-treat population was 62.4 months.
DFS events occurred in 39% of patients assigned observation and 27% of patients assigned capecitabine plus oxaliplatin (HR=0.58; 95% CI, 0.47-0.72).
Researchers reported higher rates of 5-year DFS (68% vs. 53%) and 5-year OS (78% vs. 69%) in the treatment arm. Fewer deaths occurred in the treatment arm than the observation arm (103 vs. 141; HR=0.66; 95% CI, 0.51-0.85).
“Postoperative adjuvant treatment with capecitabine plus oxaliplatin should be considered for patients with operable stage II or III gastric cancer after D2 gastrectomy,” Noh and colleagues wrote. “The relevance of our findings for patients who have had less extensive gastrectomy is unknown.”
Disclosure: The study was supported by F. Hoffmann La-Roche and Sanofi. The researchers report consultant roles with, research funding or honoraria from, employment relationships with and stock ownership in F. Hoffmann-La Roche and Sanofi-Aventis.
The CLASSIC study — which evaluated 6 months of adjuvant chemotherapy with oxaliplatin and capecitabine on a XELOX schedule compared with surveillance — was conducted exclusively in East Asia. All patients had undergone D2 lymphadenectomy and had stage II or stage III adenocarcinoma. However, in the United States, many patients with gastric cancer do not undergo that type of surgery. Thus, the effectiveness of chemotherapy alone in this country may not be as great as Noh and colleagues reported. Moreover, geographic differences in the toxicity profile of fluoropyrimidines — especially the oral agents — have been demonstrated. So the toxicity profile may be different — in fact, greater — in the United States.
Both of these concerns may dampen the enthusiasm for the postoperative chemotherapy alone approach in this country. Data from many randomized phase 3 clinical trials have established that — for locally advanced, stage II and stage III gastric adenocarcinomas — surgery is potentially curative in some patients, but outcomes are clearly improved with the addition of systemic chemotherapy. Although chemotherapy has been internationally accepted as a standard part of multimodality therapy for locally advanced, non-metastatic gastric cancer, uncertainty remains about whether the optimal approach is postoperative adjuvant chemotherapy (and, if so, which agent or agents and for how long) or perioperative therapy (as in the MAGIC trial), as well as the role — if any — of radiation.
Great geographic differences in the execution of therapy exist. Although the CLASSIC trial further confirms the benefit of postoperative adjuvant chemotherapy, it does not elucidate these important issues.