The theme of the 2019 NCCN Annual Meeting is to expand biomarker testing to guide the precise treatment of cancer, as well as new changes to colorectal cancer (CRC) guidelines. The 5-year survival rate of colorectal cancer is only 11%, and the updated treatment plan of the NCCN treatment guidelines is expected to improve survival.
Currently, the FDA has approved a variety of drugs to treat colorectal cancer, of which only four are related to genetic mutations, and biomarkers need to be tested. The 2019 update of NCCN treatment guidelines for colorectal cancer adds treatment methods based on detection of biomarkers, including EGFR, MSI-H / dMMR, BRAF + MEK, and NTRK fusion targets.
Let’s take a look at the specific important updates and heavy data:
mFOLFOXIRI + EGFR
Based on the phase II phase VOLFI trial, mFOLFOXIRI (fluorouracil + leucovorin + oxaliplatin + irinotecan) plus panitumumab for the EGFR inhibitor, for patients with unresectable metastatic colorectal cancer, these The patient’s genetic test must be: KRAS / NRAS / BRAF wild type and only the left tumor is present.
In the VOLFI trial, 96 patients with RAS wild-type metastatic colorectal cancer were randomly assigned to mFOLFOXIRI combined with panitumumab (n = 63) or only mFOLFOXIRI (n = 33) in a 2: 1 ratio. The combined panitumumab group had an effective rate of 85.7%, while mFOLFOXIRI alone was 54.5%.
MSI / MMR
Although microsatellite instability (MSI) and mismatch repair (MMR) are usually not hereditary, this does not exclude tumors induced by Lynch syndrome, which is found in 1% of BRAF V600E colorectal cancers Embodied. If you have a strong family history, you must conduct genetic testing.
The latest guidelines indicate the use of immunohistochemistry to detect the four mutant genes present in Lynch syndrome: MLH1, MSH2, MSH6 and PMS2.
In the NCCN advanced or metastatic colorectal cancer treatment guidelines, the first-line immunotherapy options for patients with MSI-H and dMMR are nivolumab (nivolumab, Opdivo) or pembrolizumab (pembrolizumab, Keytruda), or nivolumab and ipilimumab (Iraq Combined therapy with Pitimab, Yervoy). These recommendations are category 2B recommendations and apply to patients who are not suitable for a combination cytotoxic chemotherapy regimen. These immunotherapy drug options are also listed in the guidelines as second- and third-line treatment recommendations for dMMR / MSI-H patients.
For NTRK
Larotrectinib (Larotinib, Vitrakvi) is now a second-line treatment option for patients with metastatic colorectal cancer. The patient’s genetic test needs to detect a positive NTRK gene fusion. The clinical research data of the drug was published in the 2018 New England Journal of Medicine .
Therefore, in November 2018, the FDA approved the use of larotinib for the treatment of adult and pediatric patients with swollen solid tumors. As long as the patient has the NTRK gene fusion and there is no known acquired resistance mutation, the disease has metastasized and surgical resection may result Severe risk of death, there is no satisfactory alternative treatment plan or progress has occurred after treatment.
In this full cancer clinical trial, 4 patients with metastatic colorectal cancer were enrolled, and 1 patient responded well.
For BRAF and MEK
In this update of the NCCN guidelines, two second-line combination therapies for this biomarker have been added, namely:
(1) dabrafenib (dalafinib, Tafinlar; BRAF) + trametinib (trametinib, Mekinist; MEK), combined with cetuximab or panitumumab (EGFR monoclonal antibody);
(2) Encorafenib (Braftovi; BRAF) plus binimetinib (Mektovi; MEK) plus cetuximab or panitumumab.
The encorafenib / binimetinib and EGFR inhibitor treatment regimens are supported by data from the introduction of phase III BEACON trials. In 30 patients with metastatic colorectal cancer with BRAF V600E mutation, combined treatment with encorafenib / binimetinib plus cetuximab was followed up for 18.2 months, with an estimated overall survival of 15.3 months. According to local evaluation results, the combined The effective rate of treatment was 48%, and 3 patients achieved complete remission.
This update of the NCCN guidelines for colorectal cancer once again confirms the important role of genetic testing in the treatment of cancer. With one more treatment option, there is more hope! Cancer friends should stop doubting the status of genetic testing. The good news is that there are so many approved targeted drugs for colorectal cancer. Please cherish what is in your own hands.
