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Comparative Efficacy and Tolerability of Adjuvant Systemic Treatments Against Resectable Colon Cancer: A Systematic Review and Network Meta-Analysis
42 Pages Posted: 23 Sep 2019
More...Abstract
Background: Currently, 6-month FOLFOX and XELOX have been recommended as the preferred adjuvant regimens against high-risk stage 2 and stage 3 colon cancer patients. However, in consideration of growing number of novel regimens as well as disadvantages of pairwise comparisons, we conducted the first network meta-analysis to rank all regimens simultaneously and hierarchically.
Methods: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, ASCO and ESMO meeting libraries from inception to August 2019. Regarding survival and tolerability, randomized controlled trials comparing different adjuvant systemic regimens against high-risk stage 2 and stage 3 colon cancer were eligible. The Cochrane Risk of Bias Tool was utilized to assess methodological quality. Disease-free survival was primary endpoint, while overall survival and adverse events were secondary endpoints. Network calculation was based on random-effects model and relative ranking of each node was numerically indicated by P-score.
Findings: 29 trials were included, corresponding to 52818 patients. Baseline clinical features were comparable and overall risk of bias was in low level across eligible trials. Regarding disease-free survival, 12-month capecitabine monotherapy topped the hierarchy among overall population and stage 3 subgroup analysis, displaying noninferiority against 6-month XELOX (network HR 0.81 (0.60-1.10); network HR 0.79 (0.57-1.10)) and other 6-month FOLFOX regimens. Concerning overall survival, this difference was even greater, despite failing to reach statistical significance (network HR 0.71 (0.48-1.06)). Moreover, 12-month capecitabine monotherapy was more tolerable than 6-month XELOX in most of adverse events. As for comparisons between 3-month and 6-month XELOX/FOLFOX regimens, 6-month treatment was significantly better than 3-month counterpart in terms of disease-free survival among overall population (network HR 1.09 (1.01-1.18)) and stage 3 cases (network HR 1.09 (1.00-1.19)), while also featured comparable tolerability each other.
Interpretation: Taken together, in terms adjuvant systemic treatment against resectable colon cancer, especially among stage 3 patients, 12-month capecitabine monotherapy is a promising alternative to currently recommended treatment such as 6-month XELOX or FOLFOX regimen. Also, this hints that a large-scale randomized trial between 12-month capecitabine monotherapy and 6-month XELOX or FOLFOX could be arranged in the future, based on global population and with extended lymphadenectomy, to further confirm their relative efficacy and safety among high-risk stage 2 and stage 3 patients simultaneously.
Funding Statement: National Natural Science Foundation of China (81902487); National Natural Science Foundation of China (81874184).
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: This meta-analysis was registered in PROSPERO and was conducted according to Cochrane Handbook 5.1 and PRISMA for Network Meta-analysis.
Keywords: adjuvant treatment; resectable colon cancer; capecitabine; network meta-analysis; systematic review
Suggested Citation: Suggested Citation