Colorectal cancer, KRAS-mutated
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| Section editor | |
|---|---|
 |
Travis Zack, MD, PhD University of California San Francisco San Francisco, CA, USA |
Note: the page has regimens specific to BRAF-mutated colon cancer.
- See the main colorectal cancer page for general regimens.
5 regimens on this page
8 variants on this page
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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
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Colon Cancer.
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 |
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. 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
- Sotorasib (Lumakras) 240 mg PO once per day on days 1 to 14
- Panitumumab (Vectibix) 6 mg/kg IV once on day 1
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
- Sotorasib (Lumakras) 960 mg PO once per day on days 1 to 14
- Panitumumab (Vectibix) 6 mg/kg IV once on day 1
14-day cycles
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. 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
- Trifluridine and tipiracil (Lonsurf) 35 mg/m2 (maximum dose of 75 mg) PO twice per day on days 1 to 5, 8 to 12
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
- Trifluridine and tipiracil (Lonsurf) 35 mg/m2 (maximum dose of 80 mg) PO twice per day on days 1 to 5, 8 to 12
28-day cycles
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. 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-1CRC) | NR | Phase 1/2 |
Biomarker eligibility criteria
- KRAS p.G12C mutation
References
- KRYSTAL-1CRC: 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-1CRC) | NR | Phase 1/2 |
Biomarker eligibility criteria
- KRAS p.G12C mutation
Targeted therapy
- Adagrasib (Krazati) 600 mg PO twice per day
- Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg IV once on day 1
- Cycle 2 onwards: 250 mg IV once on day 1
7-day cycles
Regimen variant #2
| Study | Dates of enrollment | Evidence |
|---|---|---|
| Yaeger et al. 2022 (KRYSTAL-1CRC) | NR | Phase 1/2 |
Biomarker eligibility criteria
- KRAS p.G12C mutation
Targeted therapy
- Adagrasib (Krazati) 600 mg PO twice per day
- Cetuximab (Erbitux) 500 mg IV once on day 1
14-day cycles
References
- KRYSTAL-1CRC: 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