Revision as of 14:36, 20 February 2023

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

See the main colorectal cancer page for general regimens.

4 regimens on this page 5 variants on this page

Guidelines

ESMO

2016: Van Cutsem et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. PubMed

Older

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 PubMed

NCCN

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

Advanced or metastatic disease, second or third-line therapy

Binimetinib, Encorafenib, Cetuximab

Regimen

Study	Years 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

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 PubMed

Encorafenib & Cetuximab

Regimen

FDA-recommended dose

Study	Years 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 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

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 PubMed
BREAKWATER: NCT04607421

Irinotecan, Vemurafenib, Cetuximab

Regimen

Study	Years 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

Irinotecan (Camptosar) 180 mg/m² IV once on day 1

Targeted therapy

Vemurafenib (Zelboraf) 960 mg PO twice per day
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 contains dosing details in manuscript 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
Trametinib (Mekinist) 2 mg PO once per day
Panitumumab (Vectibix) 6 mg/kg IV once on day 1

14-day cycles

References

Study 116833: NCT01750918

@@ Line 5: / Line 5: @@
 {{#lst:Section editor transclusions|gi}}
 <big>Note: the page has regimens specific to BRAF-mutated colon cancer.
 *See the [[Colorectal_cancer|'''main colorectal cancer page''']] for general regimens.</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 14: / Line 12: @@
 |}
 {{TOC limit|limit=3}}
 =Guidelines=
 ==[http://www.esmo.org/ ESMO]==
 *'''2016:''' Van Cutsem et al. [https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Management-of-Patients-with-Metastatic-Colorectal-Cancer ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.] [https://pubmed.ncbi.nlm.nih.gov/27380959 PubMed]
 ===Older===
 *'''2013:''' Labianca et al. [http://annonc.oxfordjournals.org/content/24/suppl_6/vi64.full.pdf+html Early Colon Cancer: ESMO Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/24078664 PubMed]
 *'''2013:''' Balmaña et al. [http://annonc.oxfordjournals.org/content/24/suppl_6/vi73.full.pdf+html Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines.] [https://pubmed.ncbi.nlm.nih.gov/23813931 PubMed]
 ==[http://www.jsccr.jp/en/index.html Japanese Society for Cancer of the Colon and Rectum]==
 *'''2016:''' Watanabe et al. [https://doi.org/10.1007/s10147-017-1101-6 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer] [https://pubmed.ncbi.nlm.nih.gov/28349281 PubMed]
 ==[https://www.nccn.org/ NCCN]==
 *[https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf NCCN Guidelines - Colon Cancer]
 ==[http://www.siog.org/ SIOG]==
 *'''2014:''' Papamichael et al. [https://academic.oup.com/annonc/article/26/3/463/222917 Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013]
 =Advanced or metastatic disease, second or third-line therapy=
 ==Binimetinib, Encorafenib, Cetuximab {{#subobject:ea894c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:9134b2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 55: / Line 42: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *BRAF p.V600E
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Binimetinib (Mektovi)]] 45 mg PO twice per day
 *[[Encorafenib (Braftovi)]] 300 mg PO once per day
@@ Line 65: / Line 53: @@
 **Cycle 1: 400 mg/m<sup>2</sup> IV over 120 minutes once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22
 **Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22
 '''28-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1056/NEJMoa1908075 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31566309 PubMed] 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. [https://doi.org/10.1200/jco.20.02088 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33503393/ PubMed]
 ==Encorafenib & Cetuximab {{#subobject:ea894c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:9134b2|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 94: / Line 79: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *BRAF V600E
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Encorafenib (Braftovi)]] 300 mg PO once per day
@@ Line 102: / Line 89: @@
 **Cycle 1: 400 mg/m<sup>2</sup> IV over 120 minutes once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22
 **Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22
 '''28-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1056/NEJMoa1908075 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31566309 PubMed] 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. [https://doi.org/10.1200/jco.20.02088 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33503393/ PubMed]
 #'''BREAKWATER:''' NCT04607421
 ==Irinotecan, Vemurafenib, Cetuximab {{#subobject:aab14c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:98buya|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 128: / Line 112: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *BRAF V600E, absence of NRAS and KRAS mutations
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV once on day 1
@@ Line 136: / Line 122: @@
 *[[Vemurafenib (Zelboraf)]] 960 mg PO twice per day
 *[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV once on day 1
 '''14-day cycles'''
+</div></div>
 ===References===
 <!-- #'''Abstract:''' Kopetz S, McDonough S, Morris V, Lenz HJ, Magliocco A, Atreya C, Diaz L, Allegra C, Lieu C, Wang S, Eckhardt SG, Semrad T, Kaberle K, Guthrie K, Hochster H. Randomized phase II study of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG1406). Journal of Clinical Oncology 35, no. 4_suppl (February 01, 2017) 520-520. Published online March 21, 2017. [https://doi.org/10.1200/JCO.2017.35.4_suppl.520 link to abstract] -->
 #'''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. [https://doi.org/10.1200/jco.20.01994 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33356422/ PubMed] NCT02164916
 ==Dabrafenib, Trametinib, Panitumumab{{#subobject:abca4c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:98bhza|Variant=1}}===
 {| class="wikitable" style="width: 60%; text-align:center;"
@@ Line 152: / Line 135: @@
 ! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2015.33.15_suppl.103 Atreya et al. 2017 (Study 116833)]
+|[https://clinicaltrials.gov/ct2/show/NCT01750918 Awaiting publication (Study 116833)]
 | style="background-color:#91cf61" |Phase 1/2
 | style="background-color:#6e016b; color:white" |ORR: 26%
 |-
 |}
+''Note: efficacy and dosing details are from a [https://doi.org/10.1200/jco.2015.33.15_suppl.103 2017 ASCO abstract].''
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *BRAF V600E
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Dabrafenib (Tafinlar)]] 150 mg PO twice per day
 *[[Trametinib (Mekinist)]] 2 mg PO once per day
 *[[Panitumumab (Vectibix)]] 6 mg/kg IV once on day 1
 '''14-day cycles'''
+</div></div>
 ===References===
+#'''Study 116833:''' NCT01750918
-#'''Abstract:''' Chloe EA, Van Cutsem E, Bendell JC, Andre T, Schellens JHM, Gordon MS, McRee AJ, O'Dwyer PJ, Muro K, Tabernero J, Van Geel R, Sidhu R, Greger JG, Rangwala FA, Motwani M, Wu Y, Orford KW, and Corcoran RB. Journal of Clinical Oncology 2015 33:15_suppl, 103-103. Published online January 31, 2017. [https://doi.org/10.1200/jco.2015.33.15_suppl.103 link to abstract]
 [[Category:Colon cancer regimens]]
 [[Category:Biomarker-specific pages]]
 [[Category:Colorectal cancers]]

Difference between revisions of "Colorectal cancer, BRAF-mutated"

Revision as of 14:36, 20 February 2023

Contents

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

Biomarker eligibility criteria

Targeted therapy

References

Encorafenib & Cetuximab

Regimen

Biomarker eligibility criteria

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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