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

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
Tag: visualeditor
m (Text replacement - "http://www.esmo.org/" to "https://www.esmo.org/")
 
(63 intermediate revisions by 5 users not shown)
Line 1: Line 1:
−
{| class="wikitable" style="text-align:center; width:100%;"
+
<span id="BackToTop"></span>
−
! colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Page editor'''
+
<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
−
! colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Section editor'''
+
[[#top|Back to Top]]
−
|-
+
</div>
−
| style="background-color:#F0F0F0; width:15%" |[[File:RyanNguyen.jpg|frameless|upright=0.3|center]]
+
{{#lst:Editorial board transclusions|gi}}
−
| style="width:35%" |<big>[[User:Ryannguyen|Ryan Nguyen, DO]]<br>University of Illinois at Chicago<br>Chicago, IL</big><br>[https://www.linkedin.com/in/ryan-nguyen-0b12a432/ LinkedIn]
+
<big>Note: the page has regimens specific to BRAF-mutated colon cancer.  
−
| style="background-color:#F0F0F0; width:15%" |[[File:nkv.jpg|frameless|upright=0.3|center]]
+
*See the [[Colorectal_cancer|'''main colorectal cancer page''']] for general regimens.</big>
−
| style="width:35%" |<big>[[User:Neetavenepalli|Neeta K. Venepalli, MD, MBA]]<br>University of Illinois at Chicago<br>Chicago, IL</big>
 
−
|-
 
−
|}
 
−
<big>Note: the page has regimens specific to BRAF-mutated colon cancer.
 
−
 
 
−
*See the [[Colon_cancer|'''main colon cancer page''']] for general regimens.</big>
 
−
 
 
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
Line 19: Line 12:
 
|}
 
|}
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
−
 
 
=Guidelines=
 
=Guidelines=
−
==[http://www.esmo.org/ ESMO]==
+
'''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.'''
−
 
+
==[https://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://www.ncbi.nlm.nih.gov/pubmed/27380959 PubMed]
+
*'''2016:''' Van Cutsem et al. [https://doi.org/10.1093/annonc/mdw235 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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/23813931 PubMed]
 
  
 +
*'''2013:''' Labianca et al. [https://doi.org/10.1093/annonc/mdt354 Early Colon Cancer: ESMO Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/24078664/ PubMed]
 +
*'''2013:''' Balmaña et al. [https://doi.org/10.1093/annonc/mdt209 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]==
 
==[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]
−
*'''2016:''' Watanabe et al. [https://link.springer.com/article/10.1007%2Fs10147-017-1101-6 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer] [https://www.ncbi.nlm.nih.gov/pubmed/28349281 PubMed]
+
==NCCN==
−
 
+
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1428 NCCN Guidelines - Colon Cancer].''
−
==[https://www.nccn.org/ NCCN]==
 
−
 
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf NCCN Guidelines - Colon Cancer]
 
  
 
==[http://www.siog.org/ SIOG]==
 
==[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] [https://www.ncbi.nlm.nih.gov/pubmed/25015334 PubMed]
−
*'''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=
 
=Advanced or metastatic disease, second or third-line therapy=
 
==Binimetinib, Encorafenib, Cetuximab {{#subobject:ea894c|Regimen=1}}==
 
==Binimetinib, Encorafenib, Cetuximab {{#subobject:ea894c|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:9134b2|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|rowspan=2|[https://doi.org/10.1056/NEJMoa1908075 Kopetz et al. 2019 (BEACON CRC)]
 +
|rowspan=2|2017-2019
 +
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 +
|1a. [[#Irinotecan_.26_Cetuximab|Irinotecan & Cetuximab]]<br>1b. [[#FOLFIRI_.26_Cetuximab|FOLFIRI & Cetuximab]]
 +
| style="background-color:#1a9851" |Superior OS (co-primary endpoint)<br>Median OS: 9 vs 5.4 mo<br>(HR 0.52, 95% CI 0.39-0.70)
 +
|-
 +
|2. [[#Encorafenib_.26_Cetuximab|Encorafenib & Cetuximab]]
 +
| style="background-color:#d3d3d3" |Not reported
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
 +
''Note: the manuscript refers to 28-day cycles; this dosing is equivalent.''
 +
<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 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/m<sup>2</sup> IV over 120 minutes once on day 1
 +
**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 +
'''7-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] [https://clinicaltrials.gov/study/NCT02928224 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078423/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33503393/ PubMed]
 +
##'''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. [https://doi.org/10.1016/j.esmoop.2022.100477 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271477/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35653981/ PubMed]
 +
 +
==Encorafenib & Cetuximab {{#subobject:ea894c|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:9134b2|Variant=1}}===
 
===Regimen {{#subobject:9134b2|Variant=1}}===
−
{| class="wikitable" style="width: 100%; text-align:center;"
+
{| class="wikitable" style="color:white; background-color:#404040"
−
! style="width: 25%" |Study
+
|<small>'''FDA-recommended dose'''</small>
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |Comparator
 
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
 
|-
 
|-
−
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1908075 Kopetz et al. 2019 (BEACON)]
+
|}
−
| style="background-color:#1a9851" |Phase III (E-switch-ooc)
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
|1. Irinotecan & Cetuximab <br> 2. FOLFIRI & Cetuximab
+
!style="width: 20%"|Study
−
| style="background-color:#1a9851" |Superior OS
+
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|rowspan=2|[https://doi.org/10.1056/NEJMoa1908075 Kopetz et al. 2019 (BEACON CRC)]
 +
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 +
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-219-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 +
|-
 +
|} -->
 +
|rowspan=2|2017-2019
 +
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 +
|1a. [[#Irinotecan_.26_Cetuximab|Irinotecan & Cetuximab]]<br>1b. [[#FOLFIRI_.26_Cetuximab|FOLFIRI & Cetuximab]]
 +
| style="background-color:#1a9851" |Superior OS (co-primary endpoint)<br>Median OS: 8.4 vs 5.4 mo<br>(HR 0.60, 95% CI 0.45-0.79)
 +
|-
 +
|2. [[#Binimetinib.2C_Encorafenib.2C_Cetuximab|Binimetinib, Encorafenib, Cetuximab]]
 +
| style="background-color:#d3d3d3" |Not reported
 
|-
 
|-
 
|}
 
|}
−
'''Biomarker eligibility criteria'''
+
''Note: the manuscript refers to 28-day cycles; this dosing is equivalent.''
−
 
+
<div class="toccolours" style="background-color:#fdcdac">
−
BRAF V600E
+
====Biomarker eligibility criteria====
−
 
+
*BRAF V600E
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Encorafenib (Braftovi)]] 300 mg PO once per day on days 1 to 7
 +
*[[Cetuximab (Erbitux)]] as follows:
 +
**Cycle 1: 400 mg/m<sup>2</sup> IV over 120 minutes once on day 1
 +
**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 +
'''7-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] [https://clinicaltrials.gov/study/NCT02928224 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078423/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33503393/ PubMed]
 +
##'''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. [https://doi.org/10.1016/j.esmoop.2022.100477 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271477/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35653981/ PubMed]
 +
#'''BREAKWATER:''' [https://clinicaltrials.gov/study/NCT04607421 NCT04607421]
 +
==FOLFIRI & Cetuximab {{#subobject:ir894c|Regimen=1}}==
 +
FOLFIRI & Cetuximab: '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan, Cetuximab
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:ior4b2|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1908075 Kopetz et al. 2019 (BEACON CRC)]
 +
|2017-2019
 +
|style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Encorafenib_.26_Cetuximab|Encorafenib & Cetuximab]]<br>2. [[#Binimetinib.2C_Encorafenib.2C_Cetuximab|Binimetinib, Encorafenib, Cetuximab]]
 +
| style="background-color:#d73027" |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.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*BRAF p.V600E
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
 
+
*[[Leucovorin (Folinic acid)]] 400 mg/m<sup>2</sup> IV once on day 1
−
*[[Binimetinib (Mektovi)]] 45 mg PO twice per day
+
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, (total dose per cycle: 2800 mg/m<sup>2</sup>)
−
*[[Encorafenib (Braftovi)]] 300 mg PO once per day
+
*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV once on day 1
 +
====Targeted therapy====
 
*[[Cetuximab (Erbitux)]] as follows:
 
*[[Cetuximab (Erbitux)]] as follows:
−
**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 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 on day 8
−
**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22
+
**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8
−
 
+
'''14-day cycles'''
−
'''28-day cycles'''
+
</div></div>
−
 
 
 
===References===
 
===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] [https://clinicaltrials.gov/study/NCT02928224 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078423/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33503393/ PubMed]
 +
##'''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. [https://doi.org/10.1016/j.esmoop.2022.100477 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271477/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35653981/ PubMed]
  
−
#'''BEACON:''' 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, Tarpgaard LS, 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://www.nejm.org/doi/full/10.1056/NEJMoa1908075 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31566309 PubMed]
+
==Irinotecan & Cetuximab {{#subobject:ir894c|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
−
==Irinotecan, Vemurafenib, Cetuximab {{#subobject:aab14c|Regimen=1}}==
+
===Regimen variant #1 {{#subobject:ior4b2|Variant=1}}===
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1908075 Kopetz et al. 2019 (BEACON CRC)]
 +
|2017-2019
 +
|style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Encorafenib_.26_Cetuximab|Encorafenib & Cetuximab]]<br>2. [[#Binimetinib.2C_Encorafenib.2C_Cetuximab|Binimetinib, Encorafenib, Cetuximab]]
 +
| style="background-color:#d73027" |Inferior OS
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
===Regimen {{#subobject:98buya|Variant=1}}===
+
''Note: the manuscript refers to 28-day cycles; this dosing is equivalent.''
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
<div class="toccolours" style="background-color:#fdcdac">
−
! style="width: 25%" |Study
+
====Biomarker eligibility criteria====
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+
*BRAF p.V600E
−
! style="width: 25%" |Comparator
+
</div>
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV once on day 1
 +
====Targeted therapy====
 +
*[[Cetuximab (Erbitux)]] as follows:
 +
**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 on day 8
 +
**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8
 +
'''14-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2 {{#subobject:igcj22|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.4_suppl.520 Kopetz et al. 2017 (SWOG 1406)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8462593/ Kopetz et al. 2020 (SWOG 1406)]
−
| style="background-color:#1a9851" |Randomized Phase II (E-esc)
+
|2014-NR
−
|Irinotecan & Cetuximab
+
| style="background-color:#1a9851" |Randomized Phase 2 (C)
−
| style="background-color:#1a9851" |Superior PFS
+
|[[#Irinotecan.2C_Vemurafenib.2C_Cetuximab|Irinotecan, Vemurafenib, Cetuximab]]
 +
| style="background-color:#d73027" |Inferior PFS
 
|-
 
|-
 
|}
 
|}
−
'''Biomarker eligibility criteria'''
+
<div class="toccolours" style="background-color:#fdcdac">
−
 
+
====Biomarker eligibility criteria====
−
BRAF V600
+
*BRAF p.V600E, absence of NRAS and KRAS mutations
−
 
+
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
 
 
*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV once on day 1
 
*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV once on day 1
−
*[[Vemurafenib (Zelboraf)]] 960 mg PO twice per day
+
====Targeted therapy====
 
*[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV once on day 1
 
*[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV once on day 1
−
 
 
'''14-day cycles'''
 
'''14-day cycles'''
 +
</div></div>
  
 
===References===
 
===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] [https://clinicaltrials.gov/study/NCT02928224 NCT02928224]
−
#'''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://ascopubs.org/doi/abs/10.1200/JCO.2017.35.4_suppl.520 link to abstract]
+
##'''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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078423/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33503393/ PubMed]
−
 
+
##'''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. [https://doi.org/10.1016/j.esmoop.2022.100477 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271477/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35653981/ PubMed]
−
==Dabrafenib, Trametinib, Panitumumab{{#subobject:abca4c|Regimen=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. [https://doi.org/10.1200/jco.20.01994 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8462593/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33356422/ PubMed] [https://clinicaltrials.gov/study/NCT02164916 NCT02164916]
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
==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;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8462593/ Kopetz et al. 2020 (SWOG 1406)]
 +
|2014-NR
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|[[#Irinotecan_.26_Cetuximab|Irinotecan & Cetuximab]]
 +
| style="background-color:#1a9851" |Superior PFS (primary endpoint)
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*BRAF p.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
 +
====Targeted therapy====
 +
*[[Vemurafenib (Zelboraf)]] 960 mg PO twice per day on days 1 to 14
 +
*[[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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8462593/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33356422/ PubMed] [https://clinicaltrials.gov/study/NCT02164916 NCT02164916]
 +
==Dabrafenib, Trametinib, Panitumumab{{#subobject:abca4c|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:98bhza|Variant=1}}===
 
===Regimen {{#subobject:98bhza|Variant=1}}===
−
{| class="wikitable" style="width: 75%; text-align:center;"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
 
! style="width: 33%" |Study
 
! style="width: 33%" |Study
 
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|[https://ascopubs.org/doi/abs/10.1200/jco.2015.33.15_suppl.103 Atreya et al. 2017 (Study 116833)]
+
|[https://clinicaltrials.gov/study/NCT01750918 Awaiting publication (Study 116833)]
−
| style="background-color:#91cf61" |Phase I/II
+
| style="background-color:#91cf61" |Phase 1/2
 
| style="background-color:#6e016b; color:white" |ORR: 26%
 
| style="background-color:#6e016b; color:white" |ORR: 26%
 
|-
 
|-
 
|}
 
|}
−
'''Biomarker eligibility criteria'''
+
''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">
−
BRAF V600E
+
====Biomarker eligibility criteria====
−
 
+
*BRAF V600E
−
====Chemotherapy====
+
</div>
−
 
+
<div class="toccolours" style="background-color:#b3e2cd">
−
*[[Dabrafenib (Tafinlar)]] 150 mg PO twice per day
+
====Targeted therapy====
−
*[[Trametinib (Mekinist)]] 2 mg PO once per day
+
*[[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
 
*[[Panitumumab (Vectibix)]] 6 mg/kg IV once on day 1
−
 
 
'''14-day cycles'''
 
'''14-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
 
+
#'''Study 116833:''' [https://clinicaltrials.gov/study/NCT01750918 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://ascopubs.org/doi/abs/10.1200/jco.2015.33.15_suppl.103 link to abstract]  
 
−
 
 
 
[[Category:Colon cancer regimens]]
 
[[Category:Colon cancer regimens]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Colorectal cancers]]
 
[[Category:Colorectal cancers]]

Latest revision as of 17:45, 23 June 2024

Back to Top

Section editor
Traviszack.jpeg
 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.

4 regimens on this page
5 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

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) 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)
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

7-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. 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)
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

  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. 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
  2. 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

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

  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. 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

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-NR Randomized Phase 2 (C) Irinotecan, Vemurafenib, Cetuximab Inferior PFS

Biomarker eligibility criteria

  • BRAF p.V600E, absence of NRAS and KRAS mutations

Chemotherapy

Targeted therapy

14-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. 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
  2. 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

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 (primary endpoint)

Biomarker eligibility criteria

  • BRAF p.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
Retrieved from "https://hemonc.org/w/index.php?title=Colorectal_cancer,_BRAF-mutated&oldid=86461"