Chicago, IL—The global International Duration Evaluation of Adjuvant Chemotherapy (IDEA) study suggests that some patients with surgically resected stage III colon cancer can safely and effectively receive only 3 months of chemotherapy instead of the standard 6 months. The data were particularly convincing for patients with low-risk, surgically resected stage III colon cancer. These data set a new standard for the treatment of patients with stage III colon cancer, according to expert opinion presented at the 2017 ASCO annual meeting.
“This is a great day for patients. In this case, less is more. We are now able to spare many patients with colon cancer unnecessary side effects of an additional 3 months of chemotherapy without compromising results. This study is an excellent example of how existing treatments can be refined to work even better for patients,” said ASCO expert Nancy Baxter, MD, FRCSC, FACS, PhD, Chief, General Surgery Department, St. Michael’s Hospital, Toronto, Canada.
“I would predict that, beginning next week in the clinic, patients will be prescribed shorter duration of adjuvant chemotherapy if they have a lower risk,” said ASCO’s Chief Medical Officer, Richard Schilsky, MD, FASCO.
“These data provide a framework for discussions of risks versus benefits of individualized adjuvant therapy approaches. There was a remarkable reduction in neurotoxicity with shorter duration chemotherapy. For low-risk cancers, 3 months duration of oxaliplatin-based therapy is adequate,” stated lead investigator of the IDEA study, Axel Grothey, MD, Consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN.
The current standard of adjuvant care for stage III colon cancer is 6 months of the oxaliplatin-based chemotherapy regimen of leucovorin, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX). A 3-month chemotherapy regimen could spare patients from the debilitating toxicity of longer oxaliplatin-based treatment and reduce the use of healthcare resources.
The IDEA Study
The prospective IDEA study was based on a pooled analysis of >12,000 patients with stage III colon cancer who were enrolled in 6 parallel clinical trials in 12 countries. The study was designed to show that 3 months of chemotherapy was noninferior to 6 months, according to a prespecified definition of a more than 1.12-point difference in the upper limit of the 95% confidence interval in the 3-year disease-free survival (DFS) rate. The upper limit of the confidence interval was 1.15; therefore, the study did not meet the definition of noninferiority between the 3- and 6-month duration of chemotherapy.
Patients who received FOLFOX or CAPOX for 3 months had significantly fewer grade ≥2 neurotoxicity events compared with patients who received a 6-month regimen (P <.0001). In addition, although the 3-year DFS was comparable between the groups (74.5% vs 75.5% for 3 vs 6 months of chemotherapy), the study failed to show noninferiority in the overall patient population.
However, when patients were analyzed according to low-risk (60%) or high-risk (40%) disease, the benefits of 3 months of chemotherapy were more robust in low-risk patients than in high-risk patients. The 3-year DFS rates for low-risk patients were 83.1% for those receiving 3 months of chemotherapy and 83.3% for patients receiving 6 months; those rates were 62.7% and 64.4%, respectively, among high-risk patients.
Low-risk disease was defined as ≤3 positive lymph nodes near the primary disease site and no perforation of the outer bowel wall. Patients with high-risk colon cancer had T4 or N2 disease (ie, >7 lymph nodes), accompanied by additional high-risk features.
Patients who received FOLFOX did better with 6 months than with 3 of chemotherapy; the 3-year DFS rate was 73.6% in the 3-month group versus 76% in the 6-month group. Patients who received CAPOX had a 3-year DFS rate of 75.9% with 3 months of chemotherapy versus 74.8% with 6 months of chemotherapy.
The results regarding FOLFOX versus CAPOX are “yet unexplained,” said Dr Grothey. “No direct comparison between FOLFOX and CAPOX is possible,” he told the audience.
These findings support a risk-adapted approach, with 3 months of chemotherapy appropriate for patients with low-risk stage III colon cancer, whereas 6 months of chemotherapy is suitable for patients with high-risk disease.
“This applies to about 20,000 patients per year in the United States,” concluded Dr Grothey.