David P. Ryan, MD

The primary analysis of the IDEA trial demonstrated that low-risk stage III colorectal cancer could be acceptably treated with 3 months of capecitabine plus oxaliplatin (CAPOX), invited discussant David P. Ryan, MD, Chief of Hematology/Oncology at Massachusetts General Hospital Cancer Center, Boston, pointed out. The question that followed, he said, was “Would we be able to extend the same observations to patients with high-risk stage II disease?”

Despite some caveats described by Dr. Ryan (including the definition of high risk and the statistical noninferiority threshold), “consistent with the IDEA stage III analysis, 3 months of CAPOX was essentially the same as 6 months, but 3 months of FOLFOX [fluorouracil, leucovorin, and oxaliplatin] was definitely worse than 6 months of FOLFOX in stage II disease,” he said. Therefore, 3 months of CAPOX, but not FOLFOX, is likely sufficient for patients with high-risk stage II disease, he concluded. However, cautioned Dr. Ryan, “It’s not proven as the primary endpoint as the primary endpoint did not distinguish between regimen and combined patients receiving FOLFOX and CAPOX.”

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Dr. Ryan continued: “I find it curious that the best results numerically were obtained with 6 months of FOLFOX (86.5%), a result that could be subject to bias given that CAPOX and FOLFOX were chosen by the treating physician. I encourage the investigators to analyze this further, perhaps with propensity score matching or comparisons to real-world data.”

Dr. Ryan proposed that future studies address the individual subsets of colon cancer in the adjuvant setting, particularly those defined by different biologies, such as BRAF-mutant, microsatellite instability–high, or HER2-amplified. “Fortunately, some of these studies are underway.” ■

DISCLOSURE: Dr. Ryan has served as a consultant/advisor for MPM Capital, Maverick Therapeutics, Oncorus, TCR2, and Twentyeight-Seven Therapeutics; has received honoraria from Research to Practice and UpToDate; has ownership in MPM Capital and Acworth Pharmaceuticals; and has reported other financial relationships with Johns Hopkins University Press and McGraw Hill Chapter Royalties.