Colorectal cancer, BRAF-mutated

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Note: the page has regimens specific to BRAF-mutated colon cancer.

3 regimens on this page
3 variants on this page


Guidelines

ESMO

Older

Japanese Society for Cancer of the Colon and Rectum

NCCN

SIOG

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) 1. Irinotecan & Cetuximab
2. FOLFIRI & Cetuximab 		Superior OS
Median OS: 9.3 vs 5.9 mo
(HR 0.60, 95% CI 0.47-0.75)

Biomarker eligibility criteria

  • BRAF p.V600E

Targeted therapy

  • Binimetinib (Mektovi) 45 mg PO twice per day
  • Encorafenib (Braftovi) 300 mg PO once per day
  • 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 per day on days 8, 15, 22
    • Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22

28-day cycles

References

  1. 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 contains dosing details in manuscript 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

Encorafenib & Cetuximab

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Kopetz et al. 2019 (BEACON CRC)
ESMO-MCBS (4)
2017-2019 Phase 3 (E-RT-switch-ooc) 1. Irinotecan & Cetuximab
2. FOLFIRI & Cetuximab 		Superior OS
Median OS: 9.3 vs 5.9 mo
(HR 0.60, 95% CI 0.47-0.75)

Biomarker eligibility criteria

  • BRAF V600E

Targeted therapy

  • Encorafenib (Braftovi) 300 mg PO once per day
  • 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 per day on days 8, 15, 22
    • Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22

28-day cycles

References

  1. 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 contains dosing details in manuscript 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. BREAKWATER: NCT04607421

Irinotecan, Vemurafenib, Cetuximab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Kopetz et al. 2020 (SWOG 1406) 2014-NR Randomized Phase 2 (E-esc) Irinotecan & Cetuximab Superior PFS

Biomarker eligibility criteria

  • BRAF V600E, absence of NRAS and KRAS mutations

Chemotherapy

Targeted therapy

14-day cycles

References

  1. 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 contains dosing details in manuscript 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

14-day cycles

References

  1. Study 116833: NCT01750918
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