Neoadjuvant Chemotherapy as a Treatment Option for Operable Colon Cancer

For patients with operable colon cancer, 6 weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy may improve 2-year disease control and increase tumor down-staging and complete resection rate, according to mature results from the phase 3 FOxTROT trial.

Dion Morton, MD, University Hospital Birmingham, United Kingdom, and coauthors noted “Neoadjuvant chemotherapy has substantially improved outcomes in other gastrointestinal cancers and has potential advantages over postoperative [adjuvant chemotherapy] in colon cancer,” adding, though, “potential disadvantages of [neoadjuvant chemotherapy] … have delayed its evaluation in colon cancer.”

This trial enrolled 1053 patients with colon cancer, who were randomized on a 2-to-1 basis to receive either 6 weeks of oxaliplatin-fluoropyrimidine preoperatively plus 18 weeks postoperatively (n = 699), or 24 weeks postoperatively (n = 354). Patients with RAS wild-type tumors were further randomized on a 1-to-1 basis to either receive panitumumab or not during neoadjuvant chemotherapy. The primary end point was residual disease or recurrence within 2 years. Secondary outcomes included surgical morbidity, histopathologic stage, regression grade, completeness of resection, and cause-specific mortality.

In the neoadjuvant group, 96% started therapy and 87% completed. Of all patients, 98.1% in the neoadjuvant arm and 99.2% in the control arm underwent surgery. There was marked T and N downstaging and histologic tumor regression with neoadjuvant chemotherapy (all P < .001), and resection was more often histopathologically complete in the neoadjuvant arm (94%) than the control (89%; P < .001). At 2 years, there were fewer patients with residual or recurrent disease in the neoadjuvant arm than the control arm, 16.9% vs 21.5% (rate ratio = 0.72; 95% confidence interval [CI], 0.54 to 0.98; P = .037).

There was a strong correlation noted between tumor regression and freedom from recurrence. For patients with RAS wild-type tumors, panitumumab did not enhance the benefit seen with neoadjuvant chemotherapy. For patients with mismatch repair-deficient tumors, there was little benefit seen from neoadjuvant chemotherapy.

While 4.3% of patients in the neoadjuvant arm required expedited surgery due to obstructive symptoms, there were fewer serious postoperative complications in the neoadjuvant arm, compared to the control arm.

Dr Morton et al concluded, “Six weeks of [neoadjuvant chemotherapy] should be considered a treatment option for locally advanced colon cancer.”

Journal of Clinical Oncology associate editor, Andrew H. Ko, MD, University of California — San Francisco, California, added, “A short course of neoadjuvant chemotherapy represents a reasonable treatment option for patients with clinical stage T3+ operable, MMR-proficient colon cancer. However, further study and validation are required before adopting this as the preferred standard of care over up-front surgical resection.”

Source:

Morton D, Seymour M, Magill L, et al. Preoperative chemotherapy for operable colon cancer: Mature results of an international randomized controlled trial. J Clin Oncol. Published online January 19, 2023. doi:10.1200/JCO.22.00046