Xelox After Gastric Surgery Significantly Improves Disease-Free Survival

Yung-Jue Bang, MD

Patients with operable gastric cancer had significant improvement in disease-free survival (DFS) with adjuvant capecitabine plus oxaliplatin (Xelox) following definitive surgery, according to results of a large international trial.

When the study ended prematurely after an interim analysis, patients who received adjuvant chemotherapy had a 3-year DFS of 74% compared with 60% in patients who had only surgery. Overall survival data remain immature but showed a trend in favor of the chemotherapy arm, according to results presented at the ASCO meeting in June.

“The benefit of Xelox was observed for all disease stages,” said Yung-Jue Bang, MD, of Seoul National University in South Korea. “The safety of adjuvant Xelox in gastric cancer was consistent with the known safety profile of Xelox, with no new or unexpected findings.”

“[This trial] demonstrates the superior efficacy of adjuvant Xelox versus observation alone following D2 dissection,” he added. “The data presented support the use of adjuvant Xelox for gastric cancer.”

Surgery is the standard of care for operable gastric cancer, although recurrence rates range as high as 80%. Adjuvant chemotherapy can reduce the risk of recurrence, but no consensus exists about the optimal regimen.

Table. Stratified 3-Year Disease-Free Survival Rates

Category

Subgroup No.

Patients

HR Estimate

All

All

1035

0.58

Stage of disease

Stage II

Stage IIIA

Stage IIIB

515

377

143

0.55

0.56

0.57

Age group, y

<65

65

766

269

0.63

0.46

Sex

Female

Male

304

731

0.81

0.49

Nodal status

N0

N1/2

103

932

0.83

0.56

HR indicates hazard ratio; y, years.

Adapted from Bang et al. J Clin Oncol. 2011;29(suppl; abstr LBA4002).

Two previous studies demonstrated significant reductions in the risk of recurrence with perioperative or adjuvant chemotherapy (N Engl J Med. 2001;345:725-730 and N Engl J Med. 2006;355:11-20). However, gastric cancer specialists in Asia have questioned the adequacy of the surgery in the 2 trials, said Bang.

Conversely, some authorities consider perioperative or adjuvant therapy unnecessary following definitive (D2) dissection, he added.

Against a background of clinical uncertainty regarding the value of adjuvant therapy, investigators designed a phase III trial to resolve the issue. The trial involved patients with surgically resected stage II-IIIB gastric cancer and no prior chemotherapy or radiation therapy. Patients were randomized to 8 cycles of Xelox administered over 6 months or to observation. The primary endpoint was 3-year DFS.

An interim analysis revealed a statistically significant advantage in favor of adjuvant chemotherapy, leading to discontinuation of the trial. The final analysis included 1035 randomized patients, who had a median followup of 34.4 months.

The difference in the primary endpoint represented a 44% reduction in the hazard ratio among patients treated with Xelox (P <.0001). The observation group had a recurrence rate of 30.1% compared with 18.1% in the Xelox arm. Adjuvant chemotherapy was associated with a reduced risk of locoregional, peritoneal, and distant recurrence, as well as the overall reduction in the risk of recurrence.

Figure. CLASSIC Study Design

^aStratified by stage and country with age, sex, and nodal status as covariates.

Adapted from Bang et al. J Clin Oncol. 2011;29(suppl; abstr LBA4002).

Adverse events occurred substantially more often in the Xelox arm, including all adverse events (99% vs 52%), grade 3/4 adverse events (54% vs 6%), and serious adverse events (14% vs 7%). The most common adverse events in the Xelox arm were diarrhea (47%), nausea (66%), vomiting (39%), peripheral neuropathy (56%), neutropenia (60%), and thrombocytopenia (26%). Neutropenia was the only grade 3/4 adverse event that occurred in as many as 10% of patients (22%).

Subgroup analyses showed a consistent benefit of adjuvant chemotherapy regardless of disease stage, patient age, sex, or nodal status.

Bang Y, Kim YW, Yang H, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer: results of the phase III CLASSIC trial. J Clin Oncol. 2011;29(suppl; abstr LBA4002).