Treatment of Metastatic Colorectal Cancer: ASCO Guideline

Author(s): Van K. Morris, MD¹;Erin B. Kennedy, MHSc²;Nancy N. Baxter, MD, PhD³;Al B. Benson III, MD⁴;Andrea Cercek, MD⁵;May Cho, MD⁶;Kristen K. Ciombor, MD, MSCI⁷;Chiara Cremolini, MD, PhD⁸;Anjee Davis, MPPA⁹;Dustin A. Deming, MD¹⁰;Marwan G. Fakih, MD¹¹;Sepideh Gholami, MD¹²;Theodore S. Hong, MD¹³;Ishmael Jaiyesimi, DO¹⁴;Kelsey Klute, MD¹⁵;Christopher Lieu, MD¹⁶;Hanna Sanoff, MD, MPH¹⁷;John H. Strickler, MD¹⁸;Sarah White, MD¹⁹;Jason A. Willis, MD, PhD¹;and Cathy Eng, MD⁷

Source: DOI: 10.1200/JCO.22.01690 Journal of Clinical Oncology 41, no. 3 (January 20, 2023) 678-700.

Dr. Anjan Patel's Thoughts

Guideline of the month — ASCO guidance on mCRC. Many interesting points made.

PURPOSE

To develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC).

METHODS

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

RESULTS

Five systematic reviews and 10 randomized controlled trials met the systematic review inclusion criteria.

RECOMMENDATIONS

Doublet chemotherapy should be offered, or triplet therapy may be offered to patients with previously untreated, initially unresectable mCRC, on the basis of included studies of chemotherapy in combination with anti–vascular endothelial growth factor antibodies. In the first-line setting, pembrolizumab is recommended for patients with mCRC and microsatellite instability-high or deficient mismatch repair tumors; chemotherapy and anti–epidermal growth factor receptor therapy is recommended for microsatellite stable or proficient mismatch repair left-sided treatment-naive RAS wild-type mCRC; chemotherapy and anti–vascular endothelial growth factor therapy is recommended for microsatellite stable or proficient mismatch repair RAS wild-type right-sided mCRC. Encorafenib plus cetuximab is recommended for patients with previously treated BRAF V600E–mutant mCRC that has progressed after at least one previous line of therapy. Cytoreductive surgery plus systemic chemotherapy may be recommended for selected patients with colorectal peritoneal metastases; however, the addition of hyperthermic intraperitoneal chemotherapy is not recommended. Stereotactic body radiation therapy may be recommended following systemic therapy for patients with oligometastases of the liver who are not considered candidates for resection. Selective internal radiation therapy is not routinely recommended for patients with unilobar or bilobar metastases of the liver. Perioperative chemotherapy or surgery alone should be offered to patients with mCRC who are candidates for potentially curative resection of liver metastases. Multidisciplinary team management and shared decision making are recommended. Qualifying statements with further details related to implementation of guideline recommendations are also included.

Author Affiliations

¹University of Texas MD Anderson Cancer Center, Houston, TX; ²American Society of Clinical Oncology, Alexandria, VA; ³Melbourne School of Population and Public Health, Melbourne, Australia; ⁴Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; ⁵Memorial Sloan Kettering Cancer Center, New York, NY; ⁶UCI Health, Irvine, CA; ⁷Vanderbilt Ingram Cancer Center, Nashville, TN; ⁸University of Pisa, Pisa, Italy; ⁹Fight Colorectal Cancer, Springfield, MO; ¹⁰University of Wisconsin Carbone Cancer Center, Madison, WI; ¹¹City of Hope Helford Clinical Research Hospital, Duarte, CA; ¹²UC Davis Health, Davis, CA; ¹³Massachusetts General Hospital, Boston, MA; ¹⁴Beaumont Hospital, Royal Oak, MI; ¹⁵University of Nebraska, Omaha, NE; ¹⁶CU Medicine, Denver, CO; ¹⁷University of North Carolina, Chapel Hill, NC; ¹⁸University Medical Center, Durham, NC; ¹⁹Medical College of Wisconsin, Milwaukee, WI

Nivolumab plus Ipilimumab in Microsatellite-Instability–High Metastatic Colorectal Cancer

Here is a large phase-III well done study confirming what we knew from earlier studies, that ipilimumab plus nivolumab (Ipi+Nivo) is highly active and effective in the microsatellite instability-high metastatic colorectal cancer (MSI-high met-CRC) population. This is most likely more effective than single agent IO therapy but with higher rates of toxicity. When all things are equal, I would consider this to be the standard of care (SOC) in this context.

Oxaliplatin Added to Fluoropyrimidine/Bevacizumab as Initial Therapy for Unresectable Metastatic Colorectal Cancer in Older Patients: A Multicenter, Randomized, Open-Label Phase III Trial (JCOG1018)

This Japanese study showed no benefit with the addition of oxaliplatin to fluoropyrimidine plus bevacizumab (5FU+bev) in patients who were aged 70-74 but unfit, or >=75. Interestingly survival was actually shorter in the patients who received oxaliplatin at 21.3 vs 19.7 months.

Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study

Overall survival (OS) improvement was not statistically significant in the study arm but is a non-chemotherapy option. Patients here had tumors with MSS.

Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Versus Cetuximab as Maintenance Therapy in First-Line Therapy for RAS and BRAF Wild-Type Metastatic Colorectal Cancer: Phase III ERMES Study

Less maintenance is NOT NON-inferior, so it is inferior in patients with wild type BRAF metastatic colon cancer. So it is better to keep on the full regimen. Although, quality of life is better.

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening

Colorectal cancer screening by peripheral blood testing? This cell-free DNA assay had an 83% sensitivity and 90% specificity for advanced neoplasia. However, the issue is that this does not detect precancerous lesions well. Colonoscopy has its obvious advantages as it can both diagnose colorectal cancer as well as eradicate precancerous lesions.