Real-World Effectiveness of Adjuvant Oxaliplatin Chemotherapy in Stage III Colon Cancer: A Controlled Interrupted Time Series Analysis

Abstract

Background: The real-world effectiveness of oxaliplatin in stage III colon cancer has not been determined in a large-scale population. We aimed to assess the real-world impact of adjuvant oxaliplatin treatment on the survival of these patients. Methods: Based on Taiwan cancer registry, we evaluated 17,801 patients with resected stage III colon cancer, including 14,168 patients receiving adjuvant chemotherapy and 3,633 not receiving adjuvant chemotherapy as the control group between 2004 and 2014. We used the controlled interrupted time-series analysis to assess the three-year disease-free survival and five-year overall survival rates before (2004-2008) and after (2009-2014) the addition of oxaliplatin. Results: The introduction of oxaliplatin was associated with no significant improvement in the slopes (per half-year) of the three-year disease-free survival rate (0.2%, 95% CI: -1.7∼2.2%) and five-year overall survival rate (0.6%, 95% CI: -1.8∼3%). The patients receiving oxaliplatin-based chemotherapy also showed no significant increase in the slopes (per half-year) of the three-year disease-free survival rate (0.6%, 95% CI: -1.4∼2.6%) and five-year overall survival rate (1%, 95% CI: -1.5∼3.5%). The nonsignificant results were consistent across subgroup analyses of age (<70 vs. ≥70 years), recurrence risk (T1-3 or N1 vs. T4 or N2), and cycle of oxaliplatin use (≤6 vs. >6). However, oxaliplatin-based chemotherapy significantly increased the slope (per half-year) of the five-year OS (2%, 95% CI: 0.2∼3.8%) for patients in the high-risk group (T4 or N2). The present results were robust in several sensitivity analyses. Conclusion: Among real-world patients with stage III colon cancer, the introduction of oxaliplatin does not yield a significant improvement in survival. Future work should identify the subpopulation(s) of patients who benefit significantly from the addition of oxaliplatin.

Keywords: adjuvant chemotherapy; interrupted time series study; mortality; oxaliplatin; stage III colorectal cancer.

FIGURE 1

Survival outcomes by calendar year before and after oxaliplatin reimbursement in the entire population. (A) Three-year DFS rates for overall cohorts, (B) Five-year OS rates for overall cohorts, (C) Three-year DFS rates for oxaliplatin cohort, (D) Five-year OS rates for oxaliplatin cohort. The vertical broken lines delineate the intervention time [between quarter 4 (Q4) 2008 and Q1 2009]. DFS: disease-free survival; OS: overall survival.

FIGURE 2

Forest plot of the regression coefficients for the CITS for the overall cohort and for the oxaliplatin cohort. Please refer to eMethod 1 in the Supplement for explanation of the regression coefficients (β ₂ –β ₇).

FIGURE 3

Forest plot of the regression coefficients for the CITS for the overall cohort and for the oxaliplatin cohort with subgroups: aged <70 years; aged ≥70 years; T1-3 and N1; T4 or N2; ≤ 6 oxaliplatin cycles; >6 oxaliplatin cycles. Please refer to the eMethod 1 in the Supplement for the explanation of the regression coefficients (β ₆ , β₇).

FIGURE 4

Forest plot of the regression coefficients for the CITS for the overall cohort and for the oxaliplatin cohort with sensitivity analyses: no prior cancer history, excluding one-year transition period, excluding biweekly fluoropyrimidine treatment before the intervention. Please refer to eMethod 1 in the Supplement for explanation of the regression coefficients (β ₆ , β ₇).