Colorectal cancer, BRAF-mutated

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Note: the page has regimens specific to BRAF-mutated colon cancer. 
*See the main colorectal cancer page for general regimens.
Last updated on 2024-07-23:6 regimens on this page
7 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ESMO==
*2016: Van Cutsem et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer EuroPMC
*2013: Labianca et al. Early Colon Cancer: ESMO Clinical Practice Guidelines EuroPMC
*2013: Balmaña et al. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines EuroPMC
==Japanese Society for Cancer of the Colon and Rectum==
*2016: Watanabe et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer link to PMC article EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Colon Cancer.
==SIOG==
*2014: Papamichael et al. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013 EuroPMC
=Advanced or metastatic disease, second or third-line therapy=
==Binimetinib, Encorafenib, Cetuximab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kopetz et al. 2019 (BEACON CRC)	2017-2019 	Phase 3 (E-RT-switch-ooc)	1a. Irinotecan & Cetuximab1b. FOLFIRI & Cetuximab	Longer OS (co-primary endpoint)Median OS: 9 vs 5.4 mo(HR 0.52, 95% CI 0.39-0.70)
Kopetz et al. 2019 (BEACON CRC)	2017-2019 	Phase 3 (E-RT-switch-ooc)	2. Encorafenib & Cetuximab 	Not reported
Note: the manuscript refers to 28-day cycles; this dosing is equivalent.
====Biomarker eligibility criteria====
*BRAF p.V600E
====Targeted therapy====
*Binimetinib (Mektovi) 45 mg PO twice per day on days 1 to 7
*Encorafenib (Braftovi) 300 mg PO once per day on days 1 to 7
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV over 120 minutes once on day 1
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once on day 1
7-day cycles
===References===
#BEACON CRC: Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Schmidt Tarpgaard L, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. Epub 2019 Sep 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02928224
##Update: Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Elez E, Gollerkeri A, Maharry K, Christy-Bittel J, Kopetz S. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol. 2021 Feb 1;39(4):273-284. link to original article link to PMC article EuroPMC
##PRO analysis: Kopetz S, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Belani A, Zhang X, Tabernero J. Quality of life with encorafenib plus cetuximab with or without binimetinib treatment in patients with BRAF V600E-mutant metastatic colorectal cancer: patient-reported outcomes from BEACON CRC. ESMO Open. 2022 Jun;7(3):100477. Epub 2022 May 30. link to original article link to PMC article EuroPMC
==Encorafenib & Cetuximab==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kopetz et al. 2019 (BEACON CRC)	2017-2019 	Phase 3 (E-RT-switch-ooc)	1a. Irinotecan & Cetuximab1b. FOLFIRI & Cetuximab	Longer OS (co-primary endpoint)Median OS: 8.4 vs 5.4 mo(HR 0.60, 95% CI 0.45-0.79)
Kopetz et al. 2019 (BEACON CRC)	2017-2019 	Phase 3 (E-RT-switch-ooc)	2. Binimetinib, Encorafenib, Cetuximab 	Not reported
Note: the manuscript refers to 28-day cycles; this dosing is equivalent.
====Biomarker eligibility criteria====
*BRAF V600E
====Targeted therapy====
*Encorafenib (Braftovi) 300 mg PO once per day on days 1 to 7
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV over 120 minutes once on day 1
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once on day 1
7-day cycles
===References===
#BEACON CRC: Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Schmidt Tarpgaard L, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. Epub 2019 Sep 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02928224
##Update: Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Elez E, Gollerkeri A, Maharry K, Christy-Bittel J, Kopetz S. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol. 2021 Feb 1;39(4):273-284. link to original article link to PMC article EuroPMC
##PRO analysis: Kopetz S, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Belani A, Zhang X, Tabernero J. Quality of life with encorafenib plus cetuximab with or without binimetinib treatment in patients with BRAF V600E-mutant metastatic colorectal cancer: patient-reported outcomes from BEACON CRC. ESMO Open. 2022 Jun;7(3):100477. Epub 2022 May 30. link to original article link to PMC article EuroPMC
#BREAKWATER: NCT04607421
==FOLFIRI & Cetuximab==
FOLFIRI & Cetuximab: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan, Cetuximab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kopetz et al. 2019 (BEACON CRC)	2017-2019 	Phase 3 (C)	1. Encorafenib & Cetuximab2. Binimetinib, Encorafenib, Cetuximab	Shorter OS
Note: the manuscript refers to 28-day cycles; this dosing is equivalent. There is an error in the folinic acid dosing in the manuscript; the dose here is the one that is listed in the supplemental protocol.
====Biomarker eligibility criteria====
*BRAF p.V600E
====Chemotherapy====
*Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, (total dose per cycle: 2800 mg/m2)
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV over 120 minutes once on day 1, then 250 mg/m2 IV over 60 minutes once on day 8
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1 & 8
14-day cycles
===References===
#BEACON CRC: Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Schmidt Tarpgaard L, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. Epub 2019 Sep 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02928224
##Update: Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Elez E, Gollerkeri A, Maharry K, Christy-Bittel J, Kopetz S. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol. 2021 Feb 1;39(4):273-284. link to original article link to PMC article EuroPMC
##PRO analysis: Kopetz S, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Belani A, Zhang X, Tabernero J. Quality of life with encorafenib plus cetuximab with or without binimetinib treatment in patients with BRAF V600E-mutant metastatic colorectal cancer: patient-reported outcomes from BEACON CRC. ESMO Open. 2022 Jun;7(3):100477. Epub 2022 May 30. link to original article link to PMC article EuroPMC
==Irinotecan & Cetuximab==
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kopetz et al. 2019 (BEACON CRC)	2017-2019 	Phase 3 (C)	1. Encorafenib & Cetuximab2. Binimetinib, Encorafenib, Cetuximab	Shorter OS
Note: the manuscript refers to 28-day cycles; this dosing is equivalent.
====Biomarker eligibility criteria====
*BRAF p.V600E
====Chemotherapy====
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) as follows:
**Cycle 1: 400 mg/m2 IV over 120 minutes once on day 1, then 250 mg/m2 IV over 60 minutes once on day 8
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1 & 8
14-day cycles
===Regimen variant #2===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Kopetz et al. 2020 (SWOG 1406)	2014 to not reported	Randomized Phase 2 (C)	Irinotecan, Vemurafenib, Cetuximab	Shorter PFS
====Biomarker eligibility criteria====
*BRAF p.V600E, absence of NRAS and KRAS mutations
====Chemotherapy====
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
====Targeted therapy====
*Cetuximab (Erbitux) 500 mg/m2 IV once on day 1
14-day cycles
===References===
#BEACON CRC: Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Schmidt Tarpgaard L, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. Epub 2019 Sep 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02928224
##Update: Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Elez E, Gollerkeri A, Maharry K, Christy-Bittel J, Kopetz S. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol. 2021 Feb 1;39(4):273-284. link to original article link to PMC article EuroPMC
##PRO analysis: Kopetz S, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Belani A, Zhang X, Tabernero J. Quality of life with encorafenib plus cetuximab with or without binimetinib treatment in patients with BRAF V600E-mutant metastatic colorectal cancer: patient-reported outcomes from BEACON CRC. ESMO Open. 2022 Jun;7(3):100477. Epub 2022 May 30. link to original article link to PMC article EuroPMC
#SWOG S1406: 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. Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406). J Clin Oncol. 2021 Feb 1;39(4):285-294. Epub 2020 Dec 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02164916
==Irinotecan, Vemurafenib, Cetuximab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Kopetz et al. 2020 (SWOG 1406)	2014 to not reported	Randomized Phase 2 (E-esc)	Irinotecan & Cetuximab	Longer PFS (primary endpoint)
====Biomarker eligibility criteria====
*BRAF p.V600E, absence of NRAS and KRAS mutations
====Chemotherapy====
*Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
====Targeted therapy====
*Vemurafenib (Zelboraf) 960 mg PO twice per day on days 1 to 14
*Cetuximab (Erbitux) 500 mg/m2 IV once on day 1
14-day cycles
===References===
#SWOG S1406: 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. Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406). J Clin Oncol. 2021 Feb 1;39(4):285-294. Epub 2020 Dec 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02164916
==Dabrafenib, Trametinib, Panitumumab==
===Regimen===
Study 	Evidence 	Efficacy
Awaiting publication (Study 116833)	Phase 1/2	ORR: 26%
Note: efficacy and dosing details are from a 2017 ASCO abstract.
====Biomarker eligibility criteria====
*BRAF V600E
====Targeted therapy====
*Dabrafenib (Tafinlar) 150 mg PO twice per day on days 1 to 14
*Trametinib (Mekinist) 2 mg PO once per day on days 1 to 14
*Panitumumab (Vectibix) 6 mg/kg IV once on day 1
14-day cycles
===References===
#Study 116833: NCT01750918
Category:Colon cancer regimens
Category:Biomarker-specific pages
Category:Colorectal cancers