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 kolorektal cancer adds treatment methods based on detection of biomarkers, including EGFR, MSI-H / dMMR, BRAF + MEK, and NTRK fusion targets.
Lad os tage et kig på de specifikke vigtige opdateringer og tunge 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 er til stede.
I VOLFI-studiet blev 96 patienter med RAS-vildtype metastatisk kolorektal cancer tilfældigt tildelt mFOLFOXIRI kombineret med panitumumab (n = 63) eller kun mFOLFOXIRI (n = 33) i et 2:1-forhold. Den kombinerede panitumumab-gruppe havde en effektiv rate på 85.7 %, mens mFOLFOXIRI alene var 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.
De seneste retningslinjer angiver brugen af immunhistokemi til at påvise de fire mutante gener, der er til stede i Lynch syndrom: MLH1, MSH2, MSH6 og PMS2.
I NCCN's retningslinjer for avanceret eller metastatisk kolorektal cancerbehandling er førstelinje immunterapi 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.
Til NTRK
Larotrectinib (Larotinib, Vitrakvi) er nu en anden linje behandlingsmulighed for patienter med metastatisk kolorektal cancer. Patientens genetiske test skal påvise en positiv NTRK-genfusion. De kliniske forskningsdata for lægemidlet blev offentliggjort i 2018 New England Journal of Medicine.
Derfor godkendte FDA i november 2018 brugen af larotinib til behandling af voksne og pædiatriske patienter med hævede solide tumorer. Så længe patienten har NTRK-genfusionen, og der ikke er nogen kendt erhvervet resistensmutation, er sygdommen metastaseret, og kirurgisk resektion kan medføre Alvorlig risiko for død, der er ingen tilfredsstillende alternativ behandlingsplan, eller der er sket fremskridt efter behandlingen.
I dette fulde kliniske cancerforsøg blev 4 patienter med metastatisk kolorektal cancer inkluderet, og 1 patient reagerede godt.
Til BRAF og MEK
I denne opdatering af NCCN-retningslinjerne er der tilføjet to anden linje kombinationsterapier for denne biomarkør, nemlig:
(1) dabrafenib (dalafinib, Tafinlar; BRAF) + trametinib (trametinib, Mekinist; MEK), kombineret med cetuximab eller panitumumab (EGFR monoklonalt antistof);
(2) Encorafenib (Braftovi; BRAF) plus binimetinib (Mektovi; MEK) plus cetuximab or panitumumab.
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.
