Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update

Author(s): Nancy N. Baxter, MD, PhD¹; Erin B. Kennedy, MHSc²; Emily Bergsland, MD³; Jordan Berlin, MD⁴; Thomas J. George, MD⁵; Sharlene Gill, MD, MPH, MBA⁶; Philip J. Gold, MD⁷; Alex Hantel, MD⁸; Lee Jones, MBA⁹; Christopher Lieu, MD¹⁰; Najjia Mahmoud, MD¹¹; Arden M. Morris, MD, MPH¹²; Erika Ruiz-Garcia, MD, MS¹³; Y. Nancy You, MD, MHSc¹⁴; and Jeffrey A. Meyerhardt, MD, MPH¹⁵

Source: DOI: 10.1200/JCO.21.02538 Journal of Clinical Oncology Published online December 22, 2021. PMID: 34936379

Dr. Lucio Gordan's Thoughts

Role adjuvant chemotherapy in this setting will change significantly with incorporation of MRD evaluation post-surgery with prospective validation.

METHODS

ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.

RESULTS

Twenty-one observational studies and six randomized controlled trials met the systematic review inclusion criteria.

RECOMMENDATIONS

Adjuvant chemotherapy (ACT) is not routinely recommended for patients with stage II colon cancer who are not in a high-risk subgroup. Patients with T4 tumors are at higher risk of recurrence and should be offered ACT, whereas patients with other high-risk factors, including sampling of fewer than 12 lymph nodes in the surgical specimen, perineural or lymphatic invasion, poorly or undifferentiated tumor grade, intestinal obstruction, tumor perforation, or grade BD3 tumor budding, may be offered ACT. The addition of oxaliplatin to fluoropyrimidine-based ACT is not routinely recommended, but may be offered as a result of shared decision making. Patients with mismatch repair deficiency/microsatellite instability tumors should not be routinely offered ACT; if the combination of mismatch repair deficiency/microsatellite instability and high-risk factors results in a decision to offer ACT, oxaliplatin-containing chemotherapy is recommended. Duration of oxaliplatin-containing chemotherapy is also addressed, with recommendations for 3 or 6 months of treatment with capecitabine and oxaliplatin or fluorouracil, leucovorin, and oxaliplatin, with decision making informed by key evidence of 5-year disease-free survival in each treatment subgroup and the rate of adverse events, including peripheral neuropathy

Author Affiliations

¹University of Melbourne, Melbourne, Australia; ²American Society of Clinical Oncology, Alexandria, VA; ³UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; ⁴Vanderbilt University Medical Center, Nashville, TN; ⁵University of Florida, Gainesville, FL; ⁶BC Cancer, Vancouver, Canada; ⁷Swedish Cancer Institute, Seattle, WA; ⁸Edward Elmhurst Healthcare, Naperville, IL; ⁹Arlington, VA; ¹⁰University of Colorado Cancer Center, Aurora, CO; ¹¹Penn Medicine, Philadelphia, PA; ¹²Stanford University Medical Center, Palo Alto, CA; ¹³Instituto Nacional de Cancerologia, Mexico City, Mexico; ¹⁴University of Texas M.D. Anderson Cancer Center, Houston, TX; ¹⁵Dana-Farber Cancer Institute, Boston, MA

Disease-free survival (DFS) and time to recurrence (TTR) with circulating tumor (ct) DNA–based decision for adjuvant treatment in colon cancer stage II (CIRCULATE): An AIO (KRK-0217)/ABCSG trial.

This is the first prospective randomized trial demonstrating that ctDNA guided Adjuvant chemotherapy (ACT) improves time to recurrence (TTR) and Disease-free survival (DFS) in stage II colon cancer pts without clinical risk factors, pt with negative CtDNA had better overall survival (OS) and DFS than pts with positive CtDNA, Pts who with Positive CtDNA who and chemotherapy also had better DFS compared to the ones who underwent surveillance (77% vs 38%).

Atezolizumab plus FOLFOX for Stage III Mismatch Repair–Deficient Colon Cancer

This is a strong adjuvant signal in resected stage III dMMR colon cancer, adding atezolizumab to mFOLFOX6 cut the risk of recurrence or death in half and improved 3-year DFS from 76% to 86%. OS hasn’t separated yet, but that may be confounded by immunotherapy at relapse. Toxicity was higher, as expected, with more grade 3–4 events and immune-related adverse events (AE)s, but overall manageable. This feels practice changing for stage III dMMR disease.

Effect of invitation to colonoscopy versus faecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial

People prefer stool card over colonoscopy, and it is not inferior.

Assessment of the Addition of Oxaliplatin to Fluoropyrimidine-Based Adjuvant Chemotherapy in Patients With High-Risk Stage II Colon Cancer: An ACCENT Pooled Analysis

No oxaliplatinum in stage 2 colon cancer, even high-risk patients, by the way, De Gramont is one of the authors (father of FOLOFX reigmens).

Oxaliplatin-Based Adjuvant Chemotherapy in Older Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 12 Trials

There is more movement towards using time to relapse as an endpoint for adjuvant studies. This report highlights that there is still a role for oxaliplatin in older patients with Stage III CRC. The time to relapse was not significantly different in patients who are younger vs older. TTR is suggested as a more informative endpoint as older patients uniformly have a lower DFS and OS in most trials.