March 08 2022
Colorectal cancer (CRC) is the third most prevalent malignancy in the United States and it is estimated that more than 151,000 Americans will be diagnosed with this disease in 2022 (Siegel 2022). Despite progress in screening and early detection approaches, 20% of patients will be diagnosed with metastatic disease at initial presentation and 70% of the patients with earlier diagnosis will eventually develop metastasis (Weiser) . Despite progress in multimodality treatments, only about 20% of metastatic disease patients will be alive at five years (Loupakis 2014).
The immune system interaction with cancer is complex and variations in mechanism of resistance exist for different types of cancers.Immune checkpoint inhibitors (ICIs) reactivate the anticancer immune response by blocking the immune checkpoint protein (PD-1) or their ligands (PD-L1). Consequently, ICIs, such as anti-PD-L1 monoclonal antibody (Atezolizumab) and anti-PD-1 mAb (Pembrolizumab) may restore the immune response against different types of cancer.
A subgroup of patients with metastatic CRC have a mutations in the DNA repair system (dMMR/MSI-H)/Microsatellite Instability-High (MSI-H) that cause it not to correctly copy or fix DNA during cellular replicationleading to increase in number of mutations in the cancer cells. Clinical trial data showed that ICI is more efficacious and better tolerated than chemotherapy for patients with dMMR/MSI-H mCRC .Unfortunately, approximately 45% of these patients will fail this immunotherapy within one of therapy. Further improvement is urgently needed
The COMMIT Study (NRG-GI004/SWOG1610) was designed to test the combination of the ICI atezolizumab with the traditional chemotherapy, mFOLFOX6 and the antiangiogenic agent bevacizumab compared to single agent atezolizumab will improve progression free survival (PFS) in dMMR/MSI-H mCRC.Additionally, researchers will be comparing overall survival, objective response rates, safety profiles, duration of response and stable disease, the evaluation of the rate of PFS and disease control at 12 months, health-related quality of life, and patient-reported symptoms between treatment arms.
The COMMIT Study (NRG-GI004/SWOG1610)enrolls patients with deficient dMMR/MSI-H mCRC who have not received prior systemic treatment and stratify these patients by BRAF mutation status, metastatic disease, and any prior adjuvant therapy for colon cancer. Following stratification, these patients will be randomized 1:1 to one of two treatment arms: Atezolizumab immunotherapy alone or Atezolizumab in combination with traditional mFOLFOX6 with bevacizumab. All patients continue their treatment until disease progression and/or an unacceptable toxicity.
The COMMIT Study Co-Principal Investigators:
Caio Max Sao Pedro Rocha Lima, MD
Wake Forest University Baptist Health
crochali@wakehealth.edu
Michael Overman, MD
MD Anderson Cancer Center
moverman@mdanderson.org
The COMMIT Study (NRG-GI004/SWOG1610) is currently enrolling and has many available materials for patients who are interested in enrolling:
NRG-GI004/S1610 on Clinicaltrials.gov
ClinicalTrials.gov Identifier NCT#02997228
NRG-GI004/S1610 Patient Webpage
NRG-GI004/S1610 Patient Brochure
Citations
André, T.; Shiu, K.-K.; Kim, T.W.; Jensen, B.V.; Jensen, L.H.; Punt, C.; Smith, D.; Garcia-Carbonero, R.; Benavides, M.; Gibbs, P.; et al. Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer. N Engl J Med. 2020;383,2207–2218.
Kattan MW, Hess KR, Amin MB, Lu Y, Moons KG, Gershenwald JE, et al.CAmembers of the AJCC Precision Medicine Core. American Joint Committee on Cancer acceptance criteria for inclusion of risk models for individualized prognosis in the practice of precision medicine. Cancer J Clin. 2016;66:370–4
Loupakis, F.; Cremolini, C.; Masi; et al Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer. N. Engl J Med 2014,371, 1609–1618.
Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin 2022; 72, 7-33. Published online first: https://doi.org/10.3322/caac.21708
Weiser MR. AJCC 8th edition: colorectal cancer. Ann Surg Oncol. 2018;25(6):1454‐1455