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

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*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf NCCN Guidelines - Colon Cancer].''
 
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf NCCN Guidelines - Colon Cancer].''
 
=Advanced or metastatic disease, KRAS inhibitor-naive=
 
=Advanced or metastatic disease, KRAS inhibitor-naive=
 +
==Regorafenib monotherapy {{#subobject:b6f696|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:77bz17|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/nejmoa2308795 Fakih et al. 2023 (CodeBreaK 300)]
 +
|2022-04-19 to 2023-03-14
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Sotorasib_.26_Panitumumab|Sotorasib & Panitumumab]]; 240 mg/day sotorasib<br>2. [[#Sotorasib_.26_Panitumumab|Sotorasib & Panitumumab]]; 960 mg/day sotorasib
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''CodeBreaK 300:''' Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Saportas Y, Tran Q, Cremolini C, Pietrantonio F. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. Epub 2023 Oct 22. [https://doi.org/10.1056/nejmoa2308795 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/37870968/ PubMed] [https://clinicaltrials.gov/study/NCT05198934 NCT05198934]
 +
 
==Sotorasib & Panitumumab {{#subobject:fggj26|Regimen=1}}==
 
==Sotorasib & Panitumumab {{#subobject:fggj26|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
Line 75: Line 100:
 
*[[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===
 +
#'''CodeBreaK 300:''' Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Saportas Y, Tran Q, Cremolini C, Pietrantonio F. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. Epub 2023 Oct 22. [https://doi.org/10.1056/nejmoa2308795 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/37870968/ PubMed] [https://clinicaltrials.gov/study/NCT05198934 NCT05198934]
 +
 +
==Trifluridine and tipiracil monotherapy {{#subobject:bopoo6|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1 {{#subobject:jcjmnc|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/nejmoa2308795 Fakih et al. 2023 (CodeBreaK 300)]
 +
|2022-04-19 to 2023-03-14
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Sotorasib_.26_Panitumumab|Sotorasib & Panitumumab]]; 240 mg/day sotorasib<br>2. [[#Sotorasib_.26_Panitumumab|Sotorasib & Panitumumab]]; 960 mg/day sotorasib
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
''Note: This was the Japanese dosing variant.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Trifluridine and tipiracil (Lonsurf)]] 35 mg/m<sup>2</sup> (maximum dose of 75 mg) PO twice per day on days 1 to 5, 8 to 12
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2 {{#subobject:jcjjc7|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/nejmoa2308795 Fakih et al. 2023 (CodeBreaK 300)]
 +
|2022-04-19 to 2023-03-14
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Sotorasib_.26_Panitumumab|Sotorasib & Panitumumab]]; 240 mg/day sotorasib<br>2. [[#Sotorasib_.26_Panitumumab|Sotorasib & Panitumumab]]; 960 mg/day sotorasib
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Trifluridine and tipiracil (Lonsurf)]] 35 mg/m<sup>2</sup> (maximum dose of 80 mg) PO twice per day on days 1 to 5, 8 to 12
 +
'''28-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===

Revision as of 02:16, 19 January 2024

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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.

5 regimens on this page
8 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.

NCCN

Advanced or metastatic disease, KRAS inhibitor-naive

Regorafenib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fakih et al. 2023 (CodeBreaK 300) 2022-04-19 to 2023-03-14 Phase 3 (C) 1. Sotorasib & Panitumumab; 240 mg/day sotorasib
2. Sotorasib & Panitumumab; 960 mg/day sotorasib 		Inferior PFS

Targeted therapy

28-day cycles

References

  1. CodeBreaK 300: Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Saportas Y, Tran Q, Cremolini C, Pietrantonio F. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. Epub 2023 Oct 22. link to original article contains dosing details in manuscript PubMed NCT05198934

Sotorasib & Panitumumab

Regimen variant #1, 240 mg/day sotorasib

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fakih et al. 2023 (CodeBreaK 300) 2022-04-19 to 2023-03-14 Phase 3 (E-switch-ooc) 1a. Trifluridine and tipiracil
1b. Regorafenib 		Superior PFS (primary endpoint)
Median PFS: 3.9 vs 2.2 mo
(HR 0.58, 95% CI 0.36-0.93)
2. Sotorasib & Panitumumab; 960 mg/day sotorasib Not reported

Biomarker eligibility criteria

  • KRAS p.G12C mutation

Targeted therapy

14-day cycles


Regimen variant #2, 960 mg/day sotorasib

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fakih et al. 2023 (CodeBreaK 300) 2022-04-19 to 2023-03-14 Phase 3 (E-switch-ooc) 1a. Trifluridine and tipiracil
1b. Regorafenib 		Superior PFS (primary endpoint)
Median PFS: 5.6 vs 2.2 mo
(HR 0.49, 95% CI 0.30-0.80)
2. Sotorasib & Panitumumab; 240 mg/day sotorasib Not reported

Biomarker eligibility criteria

  • KRAS p.G12C mutation

Targeted therapy

14-day cycles

References

  1. CodeBreaK 300: Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Saportas Y, Tran Q, Cremolini C, Pietrantonio F. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. Epub 2023 Oct 22. link to original article contains dosing details in manuscript PubMed NCT05198934

Trifluridine and tipiracil monotherapy

Regimen variant #1

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fakih et al. 2023 (CodeBreaK 300) 2022-04-19 to 2023-03-14 Phase 3 (C) 1. Sotorasib & Panitumumab; 240 mg/day sotorasib
2. Sotorasib & Panitumumab; 960 mg/day sotorasib 		Inferior PFS

Note: This was the Japanese dosing variant.

Chemotherapy

28-day cycles


Regimen variant #2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fakih et al. 2023 (CodeBreaK 300) 2022-04-19 to 2023-03-14 Phase 3 (C) 1. Sotorasib & Panitumumab; 240 mg/day sotorasib
2. Sotorasib & Panitumumab; 960 mg/day sotorasib 		Inferior PFS

Chemotherapy

28-day cycles

References

  1. CodeBreaK 300: Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Saportas Y, Tran Q, Cremolini C, Pietrantonio F. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. Epub 2023 Oct 22. link to original article contains dosing details in manuscript PubMed NCT05198934

Advanced or metastatic disease, subsequent lines of therapy

Adagrasib monotherapy

Regimen

Study Dates of enrollment Evidence
Yaeger et al. 2022 (KRYSTAL-1) NR Phase 1/2

Biomarker eligibility criteria

  • KRAS p.G12C mutation

Targeted therapy

Continued indefinitely

References

  1. KRYSTAL-1: Yaeger R, Weiss J, Pelster MS, Spira AI, Barve M, Ou SI, Leal TA, Bekaii-Saab TS, Paweletz CP, Heavey GA, Christensen JG, Velastegui K, Kheoh T, Der-Torossian H, Klempner SJ. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Jan 5;388(1):44-54. Epub 2022 Dec 21. link to original article contains dosing details in abstract link to PMC article PubMed NCT03785249

Adagrasib & Cetuximab

Regimen variant #1

Study Dates of enrollment Evidence
Yaeger et al. 2022 (KRYSTAL-1) NR Phase 1/2

Biomarker eligibility criteria

  • KRAS p.G12C mutation

Targeted therapy

7-day cycles


Regimen variant #2

Study Dates of enrollment Evidence
Yaeger et al. 2022 (KRYSTAL-1) NR Phase 1/2

Biomarker eligibility criteria

  • KRAS p.G12C mutation

Targeted therapy

14-day cycles

References

  1. KRYSTAL-1: Yaeger R, Weiss J, Pelster MS, Spira AI, Barve M, Ou SI, Leal TA, Bekaii-Saab TS, Paweletz CP, Heavey GA, Christensen JG, Velastegui K, Kheoh T, Der-Torossian H, Klempner SJ. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Jan 5;388(1):44-54. Epub 2022 Dec 21. link to original article contains dosing details in abstract link to PMC article PubMed NCT03785249
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