Comparative effectiveness of oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer

Abstract

Background: The addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain.

Subjects and methods: Patients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources-the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy. Overall survival for 4060 patients diagnosed during 2004-2009 was compared with pooled data from five RCTs (the Adjuvant Colon Cancer ENdpoinTs [ACCENT] group, n = 8292). Datasets were juxtaposed but not combined using Kaplan-Meier curves. Covariate and propensity score adjusted proportional hazards models were used to calculate adjusted survival hazard ratios (HR). Stratified analyses examined effect modifiers. All statistical tests were two-sided.

Results: The survival advantage associated with the addition of oxaliplatin to adjuvant 5-FU was evident across diverse practice settings (3-year OS: RCTs, 86% [n = 1273]; SEER-Medicare, 80% [n = 1152]; CanCORS, 88% [n = 129]; NYSCR-Medicaid, 82% [n = 54]; NYSCR-Medicare, 79% [n = 180]; and NCCN, 86% [n = 438]). A statistically significant improvement in 3-year overall survival was seen in the largest cohort, SEER-Medicare, and in the NYSCR-Medicare cohort (non-oxaliplatin-containing vs oxaliplatin-containing adjuvant therapy, adjusted HR of death: pooled RCTs: HR = 0.80, 95% CI = 0.70 to 0.92, P = .002; SEER-Medicare: HR = 0.70, 95% CI = 0.60 to 0.82, P < .001; NYSCR-Medicare patients aged ≥65 years: HR = 0.58, 95% CI = 0.38 to 0.90, P = .02). The association between oxaliplatin treatment and better survival was maintained in older and minority group patients, as well as those with higher comorbidity.

Conclusion: The addition of oxaliplatin to 5-FU appears to be associated with better survival among patients receiving adjuvant colon cancer treatment in the community.

Figure 1

Effectiveness cohort assembly. CanCORS = Cancer Care Outcomes Research & Surveillance Consortium; NCCN = National Comprehensive Cancer Network Outcomes Database; NYSCR = New York State Cancer Registry; SEER = Surveillance, Epidemiology, and End Results Registry.

Figure 2

Comparison of Kaplan–Meier survival in months by treatment in stage III colon cancer patients treated with adjuvant chemotherapy by cohort. Error bars indicate 95% confidence intervals at 10-month intervals. Cox proportional hazards models were used to calculate the unadjusted hazard ratios (HRs) of death and 95% confidence intervals (CIs). Unadjusted hazard ratios were not calculated for ACCENT. All statistical tests were two-sided. A) All cohorts. Solid line = oxaliplatin; Dotted line = non-oxaliplatin. ACCENT shown in black; SEER–Medicare, green; CanCORS, red; NYSCR–Medicare, yellow; NYSCR–Medicaid, purple; NCCN, blue. B) ACCENT. C) SEER–Medicare (HR of death = 0.74, 95% CI = 0.63 to 0.86, P < .001). D) CanCORS (HR of death = 0.68, 95% CI = 0.44 to 1.04, P = .07). E) NYSCR–Medicaid (HR of death = 0.76, 95% CI = 0.34 to 1.72, P = .51). F) NYSCR–Medicare (HR of death = 0.70, 95% CI = 0.46 to 1.05, P = .08). G) NCCN (HR of death = 0.47, 95% CI = 0.18 to 1.20, P = .11). ACCENT = Adjuvant Colon Cancer End Points Group; CanCORS = Cancer Care Outcomes Research & Surveillance Consortium; NYSCR–Medicaid = New York State Cancer Registry linked to Medicaid claims; NYSCR–Medicare = New York State Cancer Registry linked to Medicare claims; NCCN = National Comprehensive Cancer Network Outcomes Database; SEER–Medicare = Surveillance Epidemiology and End Results registry linked to Medicare claims. *N < 11. Value omitted to ensure patient confidentiality.

Figure 2

Comparison of Kaplan–Meier survival in months by treatment in stage III colon cancer patients treated with adjuvant chemotherapy by cohort. Error bars indicate 95% confidence intervals at 10-month intervals. Cox proportional hazards models were used to calculate the unadjusted hazard ratios (HRs) of death and 95% confidence intervals (CIs). Unadjusted hazard ratios were not calculated for ACCENT. All statistical tests were two-sided. A) All cohorts. Solid line = oxaliplatin; Dotted line = non-oxaliplatin. ACCENT shown in black; SEER–Medicare, green; CanCORS, red; NYSCR–Medicare, yellow; NYSCR–Medicaid, purple; NCCN, blue. B) ACCENT. C) SEER–Medicare (HR of death = 0.74, 95% CI = 0.63 to 0.86, P < .001). D) CanCORS (HR of death = 0.68, 95% CI = 0.44 to 1.04, P = .07). E) NYSCR–Medicaid (HR of death = 0.76, 95% CI = 0.34 to 1.72, P = .51). F) NYSCR–Medicare (HR of death = 0.70, 95% CI = 0.46 to 1.05, P = .08). G) NCCN (HR of death = 0.47, 95% CI = 0.18 to 1.20, P = .11). ACCENT = Adjuvant Colon Cancer End Points Group; CanCORS = Cancer Care Outcomes Research & Surveillance Consortium; NYSCR–Medicaid = New York State Cancer Registry linked to Medicaid claims; NYSCR–Medicare = New York State Cancer Registry linked to Medicare claims; NCCN = National Comprehensive Cancer Network Outcomes Database; SEER–Medicare = Surveillance Epidemiology and End Results registry linked to Medicare claims. *N < 11. Value omitted to ensure patient confidentiality.