Non-inferiority complex

Top Line: Is 3 months of adjuvant chemo as good as 6 months for patients with stage III colon cancer?
The Study: The addition of oxaliplatin to 6 months of adjuvant fluoropyridimine-based chemo for advanced colon cancer improves disease-free (DFS) and overall survival (OS). But 6 months is a long time. The IDEA collaboration prospectively pooled results from 6 independent trials comparing 3 versus 6 months of chemo, each with a primary endpoint of DFS. Roughly 60% of patients received FOLFOX and 40% CAPOX. As demonstrated in prelim reporting, 3 months of chemo was NOT noninferior to 6 months. Hold up. After putting nearly 13K patients on randomized trials, the resulting DFS rates at 3 years were 74.6% versus...75.5%, aka <1% different. Turns out another underestimation of baseline risk translated to too few events to produce a mathematical result within a pre-specified confidence interval. Good thing there are plenty of subset and exploratory analyses to flesh out a paper, anyway. First, 3 months of chemo significantly reduced peripheral neuropathy from 45→15%. Second, 3 months seemed as good as 6 months of CAPOX, but 3 months seemed worse than 6 months of FOLFOX. Finally, for low risk (<T4 and <4 nodes involved) disease, 3 months was noninferior to 6 months but not so for high risk. The authors conclude this data provides a framework for “individualized” adjuvant chemo.
Bottom Line: Patients with low risk colon cancer should probably get 3 months of adjuvant chemo to reduce neuropathy without forfeiting cancer outcomes. | Grothey, N Engl J Med 2018


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