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 kolorektale kanker adds treatment methods based on detection of biomarkers, including EGFR, MSI-H / dMMR, BRAF + MEK, and NTRK fusion targets.
Kom ons kyk na die spesifieke belangrike opdaterings en swaar 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 teenwoordig.
In die VOLFI-proef is 96 pasiënte met RAS-wildtipe metastatiese kolorektale kanker ewekansig toegewys aan mFOLFOXIRI gekombineer met panitumumab (n = 63) of slegs mFOLFOXIRI (n = 33) in 'n 2: 1 verhouding. Die gekombineerde panitumumab-groep het 'n effektiewe koers van 85.7% gehad, terwyl mFOLFOXIRI alleen 54.5% was.
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.
Die jongste riglyne dui op die gebruik van immunohistochemie om die vier mutante gene wat teenwoordig is in Lynch-sindroom op te spoor: MLH1, MSH2, MSH6 en PMS2.
In die NCCN gevorderde of metastatiese kolorektale kanker behandeling riglyne, die eerste-lyn immunotherapie 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.
Vir NTRK
Larotrectinib (Larotinib, Vitrakvi) is nou 'n tweede-lyn behandeling opsie vir pasiënte met metastatiese kolorektale kanker. Die pasiënt se genetiese toets moet 'n positiewe NTRK-geensamesmelting opspoor. Die kliniese navorsingsdata van die middel is in die 2018 New England Journal of Medicine gepubliseer.
Daarom het die FDA in November 2018 die gebruik van larotinib goedgekeur vir die behandeling van volwasse en pediatriese pasiënte met geswelde soliede gewasse. Solank as wat die pasiënt die NTRK-geensamesmelting het en daar geen bekende verworwe weerstandsmutasie is nie, het die siekte metastaseer en kan chirurgiese reseksie ernstige risiko van dood tot gevolg hê, daar is geen bevredigende alternatiewe behandelingsplan of vordering het plaasgevind na behandeling nie.
In hierdie volledige kanker kliniese proef, is 4 pasiënte met metastatiese kolorektale kanker ingeskryf, en 1 pasiënt het goed gereageer.
Vir BRAF en MEK
In hierdie opdatering van die NCCN-riglyne is twee tweedelyn-kombinasieterapieë vir hierdie biomerker bygevoeg, naamlik:
(1) dabrafenib (dalafinib, Tafinlar; BRAF) + trametinib (trametinib, Mekinist; MEK), gekombineer met cetuximab of panitumumab (EGFR monoklonale teenliggaam);
(2) Encorafenib (Braftovi; BRAF) plus binimetinib (Mektovi; MEK) plus cetuximab or panitumumab.
Die enkorafenib / 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.
