March 09 2021
Approximately 150,000 new cases of colorectal cancer (CRC) will be diagnosed in the USA in 2021 and about a third will die from this disease (Siegel 2021). Approximately 22% of CRCs are metastatic at initial diagnosis, and about 70% of patients will eventually develop metastatic disease (mCRC) with estimated 5-year survival rates of only 14% (Noone 2015 and Wiser 2018). Systemic chemotherapy remains the backbone for the majority of patients with mCRC with median overall survival (OS) of approximately 30 months. Unfortunately, systemic chemotherapy may only result in a cure for a small minority of mCRC patients. Better treatments are urgently needed.
Patients with mCRC that are deficient in DNA mismatch repair (dMMR/MSI-H)/Microsatellite Instability-High (MSI-H) have a mutation in the DNA repair system that causes it not to correctly copy or fix DNA during cellular replication, which leads to a significant number of mutations in the cancer. Although this only affects approximately 5% of patients with mCRC (mCRC that is dMMR/MSI-H), these cancers can be effectively targeted with immunotherapy as a new treatment option, which is not an option for those with CRC without this defective DNA repair system. Therefore, it has become increasingly important for all patients to get tested as soon as diagnosed with CRC and thus know if they have this specific type of CRC. The testing can be done on the cancer biopsy from the diagnosis and looks for the presence or absence of these DNA repair proteins or other abnormalities in these genes as part of next generation sequencing results.
Recent clinical trial data supports the use of immunotherapy for all patients with dMMR/MSI-H mCRC, either as soon as diagnosed, or later in their treatment course. Keynote 177 clinical trial results helped to change this standard of care in 2020 by demonstrating a significant progression free survival advantage with the immune checkpoint inhibitor Pembrolizumab over traditional chemotherapy. However, in this study, a sizable number of patients still derived no benefit from the immunotherapy and ultimately needed traditional chemotherapy.
The COMMIT Study (NRG-GI004/SWOG1610) was designed to test the combination of the immunotherapy drug atezolizumab with or without the traditional chemotherapy, mFOLFOX6 with bevacizumab. The goal of this trial is to determine and compare the efficacy of both treatments based of the progression free survival (PFS) of patients on the trial. Additionally, researchers will be comparing OS, 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. This trial 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
Andre T, Shiu K, Kim TW, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study. Presented at 2020 ASCO Virtual Scientific Program; May 26, 2020. Abstract LBA4.
Noone AM, Howlader N, Krapcho M, et al. SEER Cancer Statistics Review. Bethesda, MD: National Cancer Institute; 1975-2015. Online: https://seer.cancer.gov/csr/1975_2015/
Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin 2021; 71(1):7-33. Published online first: https://doi.org/10.3322/caac.21654https://doi.org/10.3322/caac.21654
Weiser MR. AJCC 8th edition: colorectal cancer. Ann Surg Oncol. 2018;25(6):1454‐1455