Section editor
	Travis Zack, MD, PhD University of California San Francisco San Francisco, CA, USA LinkedIn

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 PubMed

2013: Labianca et al. Early Colon Cancer: ESMO Clinical Practice Guidelines PubMed
2013: Balmaña et al. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines PubMed

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 PubMed

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 PubMed

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 & Cetuximab 1b. FOLFIRI & Cetuximab	Superior 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 PubMed NCT02928224
1. 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 PubMed
2. 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 PubMed

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 & Cetuximab 1b. FOLFIRI & Cetuximab	Superior 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 PubMed NCT02928224
1. 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 PubMed
2. 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 PubMed
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 & Cetuximab 2. Binimetinib, Encorafenib, Cetuximab	Inferior 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 PubMed NCT02928224
1. 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 PubMed
2. 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 PubMed

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 & Cetuximab 2. Binimetinib, Encorafenib, Cetuximab	Inferior 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	Inferior 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 PubMed NCT02928224
1. 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 PubMed
2. 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 PubMed
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 PubMed 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	Superior 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 PubMed 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

Colorectal cancer, BRAF-mutated

Guidelines

ESMO

Japanese Society for Cancer of the Colon and Rectum

NCCN

SIOG

Advanced or metastatic disease, second or third-line therapy

Binimetinib, Encorafenib, Cetuximab

Regimen

Biomarker eligibility criteria

Targeted therapy

References

Encorafenib & Cetuximab

Regimen

Biomarker eligibility criteria

Targeted therapy

References

FOLFIRI & Cetuximab

Regimen

Biomarker eligibility criteria

Chemotherapy

Targeted therapy

References

Irinotecan & Cetuximab

Regimen variant #1

Biomarker eligibility criteria

Chemotherapy

Targeted therapy

Regimen variant #2

Biomarker eligibility criteria

Chemotherapy

Targeted therapy

References

Irinotecan, Vemurafenib, Cetuximab

Regimen

Biomarker eligibility criteria

Chemotherapy

Targeted therapy

References

Dabrafenib, Trametinib, Panitumumab

Regimen

Biomarker eligibility criteria

Targeted therapy

References

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