Three Versus 6 Months of Adjuvant Oxaliplatin-Fluoropyrimidine Chemotherapy for Colorectal Cancer: Final Results of SCOT-An International, Randomized, Phase III, Noninferiority Trial.
Iveson T., Saunders MP., Kelly C., Kerr RS., Cassidy J., Hollander NH., Tabernero J., Haydon A., Glimelius B., Harkin A., Allan K., McQueen J., Pearson S., Boyd KA., Briggs AH., Waterston A., Medley L., Ellis R., Dhadda AS., Harrison M., Falk S., Rees C., Olesen RK., Propper D., Bridgewater J., Azzabi A., Cunningham D., Hickish T., Gollins S., Wasan HS., Church D., Domingo E.
Adjuvant chemotherapy for colorectal cancer (CRC) with oxaliplatin and fluoropyrimidine was traditionally given for 6 months but is associated with cumulative peripheral neuropathy. The SCOT study (ISRCTN59757862) was an international, randomized, phase III, noninferiority trial investigating treatment reduction from 6 to 3 months. It originally reported noninferior disease-free survival with reduced toxicity and improved quality of life for 3 months of treatment in 6,088 patients. Here, we report overall survival (OS) with 38 months of additional follow-up. Patients with high-risk stage II and stage III CRC were assigned (1:1) to receive 3 or 6 months of either capecitabine and oxaliplatin (CAPOX) or infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX; bolus and infused fluorouracil with oxaliplatin) that were selected before random assignment. With a median of 113 months follow-up and 1,255 OS events, 5-year OS for 3 versus 6 months of treatment was 82.4% in both groups (hazard ratio, 0.96; 95% CI, 0.8 to 1.07), proving noninferiority of 3 months of treatment. Noninferiority of 3 months of treatment for OS was also shown in 1,087 patients with rectal cancer. The duration effect is regimen-dependent with noninferiority shown for CAPOX but not for FOLFOX. In summary, SCOT has shown noninferiority for OS with 3 months of adjuvant chemotherapy treatment, which should be recommended for most patients.