Adjuvant Chemo Noninferor at 3 Months Vs 6 Months in Stage II/III CRC

Adding 3 months of adjuvant chemotherapy was noninferior to the traditional 6 months of adjuvant chemotherapy that is typically given to patients with high-risk stage II and stage III colorectal cancer, according to final results from the international, randomized phase 3 SCOT trial (ISRCTN59757862) published in the Journal of Clinical Oncology.¹

In the trial, patients were randomly assigned to receive either capecitabine (Xeloda) and oxaliplatin (CAPOX) or fluorouracil, leucovorin, and oxaliplatin (FOLFOX). Of 6088 total patients, of whom 4109 received CAPOX and 1979 received FOLFOX, the 5-year disease-free survival (DFS) was 72.9% for patients who received both 3 months and 6 months of adjuvant chemotherapy (HR, 0.99; 95% CI, 0.90-1.09); a total of 1747 DFS events were noted. The 5-year overall survival (OS) was 82.4% with both 3 and 6 months of treatment (HR, 0.96; 95% CI, 0.86-1.07); a total of 1255 OS events occurred. The investigators highlighted that the upper margin of the 95% CI formally confirmed noninferiority of 3 months of treatment (P = .0033).

A secondary end point analysis demonstrated that, among those who received CAPOX, patients who received 3 months of treatment had a 5-year OS of 82.5% vs 81.4% in patients who received 6 months of treatment (HR, 0.90; 95% CI, 0.78-1.03). Among those who received FOLFOX, the 5-year OS rates were 82.0% and 84.4%, respectively (HR, 1.10; 95% CI, 0.93-1.34). For OS, the noninferiority of 3 months of treatment was confirmed with CAPOX (P = .0052) but not FOLFOX (P = .38).

Patients who had stage III colon cancer had an OS of 81.0% in both the 3- and 6-month groups. Among low-risk cases, the 5-year OS was 91.0% with 3 months of treatment and 89.1% with 6 months of treatment (HR, 0.87; 95% CI, 0.70-1.07). In high-risk cases, the 5-year OS rates were 69.5% and 71.7%, respectively (HR, 1.02; 95% CI, 0.88-1.17). Among patients with stage III disease, 3 months of treatment was shown to be noninferior for low-risk patients (P = .0071) but not high-risk patients (P = .072).

Additionally, in the 1101 patients with rectal cancer, the OS was 88.6% with 3 months of treatment and 87.3% with 6 months of treatment (HR, 0.74; 95% CI, 0.55-1.00). Among those who received CAPOX, the OS rates were 89.8% vs 88.1%, respectively (HR, 0.67; 95% CI, 0.47-0.97); with FOLFOX, the OS rates were 86.4% and 85.6% (HR, 0.91; 95% CI, 0.55-1.53).

“These final SCOT results provide further evidence that 3 months of adjuvant chemotherapy can be recommended for most localized colon or rectal cancers, with no statistically significant OS advantage of 6 months of treatment in any cohort,” wrote lead study author Timothy Iveson, MD, FRCP, from the University of Southampton in Southampton, United Kingdom, and coauthors.¹

In the primary reported analysis, more thorough information on the trial design were shared.² Patients were randomly assigned, in a 1:1 ratio, to receive chemotherapy—CAPOX or FOLFOX—for either 3 months (n = 3044) or 6 months (n = 3044).

Eligible patients were 18 years or older and had undergone curative resection for high-risk stage II or stage III adenocarcinoma of the colon or rectum; they also had a WHO performance status of 0 or 1, adequate organ function, and at least 5 years of life expectancy. They were enrolled within 11 weeks of surgery and treatment began within 2 weeks of randomization.

The primary end point of the trial was DFS; secondary end points were OS, safety, quality of life, and cost-effectiveness.

Safety was also reported in the primary analysis, with 434 patients each evaluable for 3 and 6 months of treatment. The most common grade 3 to 5 adverse events (AEs) were sensory neuropathy, diarrhea, neutropenia, fatigue, pain, nausea, and hand-foot syndrome. The group of patients who received treatment for 6 months had a significantly higher incidence of diarrhea (P = .033), neutropenia (P = .031), pain (P = .014), hand-foot syndrome (P = .031), and sensory neuropathy (P <.0001).

“When deciding on treatment duration for high-risk stage III disease, it is important to emphasize that there is no significant OS advantage for 6 months of therapy, and to highlight the additional toxicities (particularly cumulative neuropathy) and hospital visits. Extended chemotherapy increases pressure on delivery units and combined with management of excess toxicities, increases financial burden,” the authors concluded.¹

References

1. Iveson T, Saunders MP, Kelly C, et al. Three versus 6 months of adjuvant oxaliplatin-fluoropyrimidine chemotherapy for colorectal cancer: final results of SCOT-An international, randomized, phase III, noninferiority trial. J Clin Oncol. Published online January 9, 2026. doi:10.1200/JCO-25-00621
2. Iveson TJ, Kerr RS, Saunders MP, et al. 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2018;19(4):562-578. doi:10.1016/S1470-2045(18)30093-7