In an analysis of data from the IDEA collaboration reported in the Journal of Clinical Oncology, Timothy J. Iveson, MD, FRCP, and colleagues found that 3 months (vs 6 months) of adjuvant CAPOX (capecitabine and oxaliplatin) may be a potential treatment option for patients with high-risk colorectal cancer.
As stated by the investigators, “As oxaliplatin results in cumulative neurotoxicity, reducing treatment duration without loss of efficacy would benefit patients and health-care providers.”
“Although noninferiority has not been demonstrated in the overall population, the convenience, reduced toxicity, and cost of 3-month adjuvant CAPOX suggest it as a potential option for high-risk stage II colon cancer if oxaliplatin-based chemotherapy is suitable. The relative contribution of the factors used to define high-risk stage II disease needs better understanding.”— Timothy J. Iveson, MD, FRCP, and colleagues
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Study Details
The analysis included data from four of six trials in the IDEA collaboration that included patients with high-risk stage II colorectal cancer. Per physician or patient choice, patients received adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX. They were randomly assigned to 3 vs 6 months of treatment between June 2007 and January 2017. The primary endpoint was disease-free survival, with noninferiority of 3-month treatment defined as a hazard ratio (HR) of < 1.2 vs 6-month treatment. Analysis was performed in the modified intention-to-treat population, consisting of patients who received at least one dose of study chemotherapy.
Key Findings
Among 3,273 eligible patients, 1,254 (38%) received FOLFOX, with 619 receiving 3 months and 635 receiving 6 months of treatment. A total of 2,019 (62%) received CAPOX, with 1,020 receiving 3 months and 999 receiving 6 months of treatment. Median follow-up at time of analysis in December 2018 was 60.2 months.
Among all patients, 5-year disease-free survival was 80.7% in the 3-month groups vs 83.9% in the 6-month groups (HR = 1.17, 80% confidence interval [CI] = 1.05–1.31; P for noninferiority = .39).
In subgroup analysis, the choice of chemotherapy group was the only group that exhibited a marked difference in outcome, although a test of interaction was not significant (P = .07). Hazard ratios for 3 vs 6 months of treatment were 1.02 (80% CI = 0.88–1.17) among patients receiving CAPOX and 1.41 (80% CI = 1.18–1.68) among those receiving FOLFOX.
Overall, patients receiving 6 months of treatment had a significantly higher rate of adverse events, particularly diarrhea, peripheral neuropathy (grade ≥ 2 in 36% vs 13%), hand-foot syndrome, and mucositis.
Data from three studies in the analysis that collected data on six risk factors showed significantly worse disease-free survival for patients with two or more risk factors vs one. Data from all four studies in the analysis showed worse outcomes among patients with stage T4 vs stage T3 disease.
The investigators concluded, “Although noninferiority has not been demonstrated in the overall population, the convenience, reduced toxicity, and cost of 3-month adjuvant CAPOX suggest it as a potential option for high-risk stage II colon cancer if oxaliplatin-based chemotherapy is suitable. The relative contribution of the factors used to define high-risk stage II disease needs better understanding.”
Dr. Iveson, of University Hospital Southampton NHS Foundation Trust, United Kingdom, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
