Issue: May 25, 2021
Disclosures: Barber reports no relevant financial disclosures.
May 25, 2021
3 min read

IDEA trial establishes new standard of care for stage III colon cancer

Issue: May 25, 2021
Disclosures: Barber reports no relevant financial disclosures.
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For years, standard treatment for patients with stage III colon cancer has been adjuvant chemotherapy for 6 months following resection.

Researchers designed the IDEA (International Duration Evaluation of Adjuvant therapy) trial to evaluate the benefit of 3 months vs. 6 months of chemotherapy with either FOLFOX (leucovorin, 5-FU and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) for high- and low-risk stage III colon cancer.

How to clinically apply and interpret the previously reported 3-year DFS from the study had been debated because noninferiority of the shorter-duration adjuvant chemotherapy was not proven for the whole population. Now, with OS data from 5 years of follow-up, we can confidently recommend 3 months of CAPOX as the standard adjuvant care for stage III colon cancer.

Study results

The IDEA trial is the largest prospective, randomized analysis to date of adjuvant therapy among patients with colon cancer. Completed in 2015, it is a pooled analysis of six randomized phase 3 clinical trials with over 13,000 patients evaluated over 8 years. Due to this large population size, the statistical design of the prospective analysis served as a strength of the study.

Kristin Barber, FNP-BC, AOCNP
Kristin Barber

Researchers randomly assigned patients to 3 months or 6 months of either FOLFOX or CAPOX chemotherapy. DFS served as the study’s primary endpoint, with OS as the secondary endpoint.

Findings showed 5-year OS rates of 82.4% among patients who received 3 months of therapy compared with 82.8% among patients who received 6 months of therapy (HR = 1.02; 95% CI, 0.95-1.11). Five-year DFS was not significantly different between the 3- and 6-month CAPOX groups (HR = 0.98; 95% CI, 0.88-1.08), but was significantly improved with 6 months vs. 3 months of FOLFOX (HR = 1.16; 95% CI, 1.07-1.26).

Although the IDEA study did not meet the endpoint of noninferiority in terms of OS, expert analysis and clinicians have recognized that the absolute 0.4% difference in 5-year OS should be considered clinically nonsignificant, supporting the use of 3 months of adjuvant CAPOX for most patients with stage III colorectal cancer.

Clinical implications

The most common chronic toxicity experienced from adjuvant chemotherapy in colorectal cancer is peripheral neuropathy, which can be long lasting and irreversible. Longer duration and exposure to oxaliplatin has been known to cause this distressing side effect. Incidence rates of grade 3 or greater neurotoxicity in IDEA were 3% with 3 months of CAPOX compared with 9% with 6 months of CAPOX.

In addition to the reduction in peripheral neuropathy, the use of CAPOX does not require implantation of a vascular access device or an infusion pump. A 3-month regimen also reduces other toxicities including diarrhea, neutropenia, thrombocytopenia, nausea, mucositis, fatigue and hand-foot syndrome. Because the average age of patients with colorectal cancer is older than 65 years, reduction of these side effects can substantially improve quality of life and decrease health care costs.

If the FOLFOX regimen is chosen, the slight DFS benefit with 6 months of therapy — especially for high-risk groups — must be weighed with the increase in peripheral neuropathy rates. The rate of grade 3 or greater peripheral neuropathy is 3% with 3 months of FOLFOX chemotherapy compared with 16% with 6 months of the same chemotherapy.

Changing landscape

Results of the IDEA collaboration have led to updated guidelines for oncology practitioners. The collaboration also has provided benefit to many future patients by decreasing the amount and duration of chemotherapy they are likely to receive. This will result in less peripheral neuropathy and hopefully fewer long-term complications for survivors of colorectal cancer.

The landscape of adjuvant therapy is changing constantly. Clinical trials are now trying to evaluate the role and predictive ability of circulating tumor DNA. Current analyses are showing potential use of cell-free DNA in colon cancer for monitoring postoperative recurrence; monitoring treatment response; identifying therapeutic resistance in patients with metastatic disease (like BRAF mutations and their resistance); and diagnosis of patients with early-stage disease.

Solid tumor clinicians and researchers are learning a lot from our liquid tumor counterparts. The ease of using serial blood tests over repeat biopsies and invasive procedures is allowing for application of these tests to daily clinical care. In the future, these genetic tumor tests will likely shape the duration of treatment and capture those patients at risk for relapse in earlier-stage colorectal cancer.

The NRG Oncology COBRA trial is one example of a study looking to answer key questions. Researchers of this study are looking at using cell-free DNA as a predictive biomarker for adjuvant therapy in patients with stage II colon cancer.

The future is exciting, and we all need to contribute to ongoing research to answer these very important clinical questions.


André T, et al. Lancet Oncol. 2020;doi:10.1016/S1470-2045(20)30527-1.

Bi F, et al. Am J Transl Res. 2020;12(3):1044-1055.

Iveson TJ, et al. Lancet Oncol. 2018;doi:10.1016/S1470-2045(18)30093-7.

Morris VK, et al. J Clin Oncol. 2021;doi:10.1200/JCO.2021.39.3_suppl.TPS148.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 2.2021; Jan. 2021. Available at: Accessed May 3, 2021.

For more information:

Kristin Barber, FNP-BC, AOCNP, is the clinical educator outpatient advanced practice clinician and an advanced practice clinician in gastrointestinal oncology at University of Utah Huntsman Cancer Institute. She can be reached at