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Ref Type Journal Article
PMID (33356422)
Authors Kopetz S, Guthrie KA, Morris VK, Lenz HJ, Magliocco AM, Maru D, Yan Y, Lanman R, Manyam G, Hong DS, Sorokin A, Atreya CE, Diaz LA, Allegra C, Raghav KP, Wang SE, Lieu CH, McDonough SL, Philip PA, Hochster HS
Title Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406).
Journal Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Vol 39
Issue 4
Date 2021 Feb 01
URL
Abstract Text BRAFV600E mutations are rarely associated with objective responses to the BRAF inhibitor vemurafenib in patients with metastatic colorectal cancer (CRC). Blockade of BRAFV600E by vemurafenib causes feedback upregulation of EGFR, whose signaling activities can be impeded by cetuximab.One hundred six patients with BRAFV600E-mutated metastatic CRC previously treated with one or two regimens were randomly assigned to irinotecan and cetuximab with or without vemurafenib (960 mg PO twice daily).Progression-free survival, the primary end point, was improved with the addition of vemurafenib (hazard ratio, 0.50, P = .001). The response rate was 17% versus 4% (P = .05), with a disease control rate of 65% versus 21% (P < .001). A decline in circulating tumor DNA BRAFV600E variant allele frequency was seen in 87% versus 0% of patients (P < .001), with a low incidence of acquired RAS alterations at the time of progression. RNA profiling suggested that treatment benefit did not depend on previously established BRAF subgroups or the consensus molecular subtype.Simultaneous inhibition of EGFR and BRAF combined with irinotecan is effective in BRAFV600E-mutated CRC.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E colorectal cancer sensitive Cetuximab + Irinotecan + Vemurafenib Phase II Actionable In a Phase II trial (SWOG1406), addition of Zelboraf (vemurafenib) to Camptosar (irinotecan) plus Erbitux (cetuximab) improved progression-free survival (4.4 vs. 2.0 mo, HR 0.50, p=0.001), response rate (17% vs 4%, p=0.05), and disease control rate (67% vs. 22%, p<0.001) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 33356422; NCT02164916). 33356422