Dr. Timothy Iveson presents Abstract 3502.
The SCOT trial, presented during an Oral Abstract Session on June 5 by Timothy Iveson, MD, of the University Hospital Southampton NHS Foundation Trust, in the United Kingdom, was the largest contributor to the IDEA collaboration. Results from that collection of six trials were presented during the Plenary Session (Abstract LBA1), on June 4. The individual trials differed somewhat in their findings, but the combined study found that, although 3 months of oxaliplatin-based adjuvant chemotherapy is not noninferior to 6 months in the entire cohort of patients with stage III colon cancer, there may be differences that are based on the selected oxaliplatin-containing regimen.
SCOT trial investigators planned for 9,500 patients, but slow accrual resulted in 6,088 patients across 244 centers in six countries. This was the only trial included in IDEA that allowed patients with cancer of the rectum to participate; they made up approximately 18% of the total. Patient characteristics were well matched between a group randomly assigned to receive 3 months of investigator-choice chemotherapy (CAPOX or FOLFOX) or 6 months.
In the 3-month group, 67.4% received CAPOX, and 32.6% received FOLFOX. In the 6-month group, rates were similar at 67.5% and 32.5%, respectively.
The primary endpoint of disease-free survival (DFS) was met for noninferiority. The 3-year DFS rate was 76.7% in those who received 3 months of chemotherapy compared with 77.1% in those who received 6 months. This difference of 0.4% yielded a hazard ratio (HR) of 1.006 (95% CI [0.909, 1.114]; noninferiority p = 0.012).
The results differed for each of the two regimens. The 3-year DFS rate in the group who received 3 months of CAPOX (4,092 patients) was 76.9%, and it was 76.1% in the group who received 6 months (HR 0.944, 95% CI [0.835, 1.067]; noninferiority p = 0.002). However, in those who received FOLFOX (1,973 patients), the 3-year DFS rate was 76.4% with 3 months of therapy and was 79.2% with 6 months (HR 1.157, 95% CI [0.964, 1.398]; noninferiority p = 0.591).
The noninferiority also depended on stage III risk group. Those with T1-3N1 disease (2,663 patients) had a 3-year DFS rate of 85.3% with 3 months of therapy and a rate of 84.0% with 6 months (HR 0.907, 95% CI [0.749, 1.097]; noninferiority p = 0.011). Those with T4 or N2 disease (2,283 patients), in contrast, had a 3-year DFS rate of 63.0% with 3 months of therapy and a rate of 64.9% with 6 months of therapy (HR 1.069, 95% CI [0.935, 1.223]; noninferiority p = 0.206).
As with other trials in the IDEA collaboration, the longer duration of therapy resulted in greater toxicity. With FOLFOX, the 6-month group had a 16.8% rate of grade 3 or 4 peripheral neuropathy compared with 4.0% in the 3-month group. Those rates were similar with CAPOX: 16.3% and 4.1%, respectively.
“Overall, SCOT met its noninferiority target for 3 months of adjuvant chemotherapy, and, therefore, 3 months treatment should now be considered for many patients,” Dr. Iveson concluded.
The discussant for the session, Jeffrey A. Meyerhardt, MD, MPH, FASCO, of the Dana-Farber Cancer Institute, stressed that even multiple years later peripheral neuropathy is “appreciably worse” with 6 months of treatment with oxaliplatin.
On the basis of this trial and the full IDEA results, he said that, for his next patient with T4 or N2 disease, he will likely offer 6 months of FOLFOX therapy. For a patient with T1-3N1 disease, however, he will offer 3 months of CAPOX or FOLFOX and will stress that the data appear stronger for CAPOX. Discussion about the differences in toxicities and the logistics of regimen administration with patients is an important part of the decision-making process, he noted.