Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581

Abstract

Purpose: We conducted a randomized trial comparing adjuvant treatment with edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied patient- and tumor-specific markers of treatment outcome.

Patients and methods: After surgical resection, patients with stage II colon cancer were randomly assigned to either five infusions of edrecolomab at 28-day intervals or observation without adjuvant therapy.

Results: Final accrual included 1,738 patients; 865 patients received edrecolomab, and 873 patients were observed without adjuvant treatment. Median follow-up time was 7.9 years. There were no significant outcome differences between study arms (overall survival [OS], P = .71; disease-free survival, P = .64). The combined 5-year all-cause OS was 0.86 (95% CI, 0.84 to 0.88), and the combined 5-year disease-specific OS was 0.93 (95% CI, 0.91 to 0.94). The relationships between demographic and histopathologic factors and survival differed for all-cause and disease-specific survival outcomes, but no combined prognostic factor model was found to adequately classify patients at higher risk of recurrence or death as a result of colon cancer.

Conclusion: Edrecolomab did not prolong survival. Consequently, this large study with a long duration of follow-up provided unique data concerning the natural history of resected stage II colon cancer. Prognostic factors identified in previous retrospective and pooled analyses were associated with survival outcomes in this stage II patient cohort. Results from ongoing molecular marker studies may enhance our ability to determine the risk profile of these patients.

Fig 1.

Patient flow diagram for Cancer and Leukemia Group B 9581 study. MoAb 17-1A, edrecolomab.

Fig 2.

Kaplan-Meier estimates of (A) overall survival (all-cause death) by treatment (stratified proportional hazards, P = .71) and (B) disease-free survival (documented recurrence of primary colon cancer or death from any cause) by treatment (stratified proportional hazards, P = .64).

Fig 3.

Smoothing splines of (A) the log hazard for disease-specific disease-free survival by number of nodes examined truncated at 32 nodes, representing 95% of the data, and (B) the log hazard for disease-specific overall survival by age at trial entry with 95% confidence bands.

Fig A1.

Kaplan-Meier estimates of all-cause and disease-specific overall survival for all randomly assigned patients (N = 1,713).

Fig A2.

Cumulative probability of experiencing the cause-specific event before time t by years from study activation (disease-related and other causes of death) for (A) sex, (B) race, and (C) age.