Non-small cell lung cancer, KRAS-mutated
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| Page editor | Section editor | ||
|---|---|---|---|
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Eric K. Singhi, MD MD Anderson Cancer Center Houston, TX  esinghimd
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Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN AmitKulkarniMD
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Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.
2 regimens on this page
2 variants on this page
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Guidelines
ASCO
- 2022: Singh et al. Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline
Advanced or metastatic disease, subsequent lines of therapy
Adagrasib monotherapy
Regimen
| FDA-recommended dose |
| Study | Dates of enrollment | Evidence | |
|---|---|---|---|
Jänne et al. 2022 (KRYSTAL-1)
|
2020 | Phase 2 (RT) |
Biomarker eligibility criteria
- KRAS p.G12C mutation
References
- KRYSTAL-1: Jänne PA, Riely GJ, Gadgeel SM, Heist RS, Ou SI, Pacheco JM, Johnson ML, Sabari JK, Leventakos K, Yau E, Bazhenova L, Negrao MV, Pennell NA, Zhang J, Anderes K, Der-Torossian H, Kheoh T, Velastegui K, Yan X, Christensen JG, Chao RC, Spira AI. Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRASG12C Mutation. N Engl J Med. 2022 Jul 14;387(2):120-131. Epub 2022 Jun 3. link to original article PubMed NCT03785249
Docetaxel monotherapy
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Blumenschein et al. 2015 (GSK 114653) | 2011-2012 | Randomized Phase 2 (C) | Trametinib | Did not meet primary endpoint of PFS |
| Jänne et al. 2017 (SELECT-1) | 2013-2016 | Phase 3 (C) | Docetaxel & Selumetinib | Did not meet primary endpoint of PFS |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
Supportive therapy
- Per JMEI: Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2 (3 days)
- Per Chem et al. 2006: Dexamethasone (Decadron) by the following split schedule:
- 8 mg PO once per day on days 1, 8, 15; 12 hours prior to Docetaxel (Taxotere)
- 10 mg IV once per day on days 1, 8, 15; 30 minutes prior to Docetaxel (Taxotere)
- 8 mg PO once per day on days 1, 8, 15; 12 hours after Docetaxel (Taxotere)
21-day cycles
References
- GSK 114653: Blumenschein GR Jr, Smit EF, Planchard D, Kim DW, Cadranel J, De Pas T, Dunphy F, Udud K, Ahn MJ, Hanna NH, Kim JH, Mazieres J, Kim SW, Baas P, Rappold E, Redhu S, Puski A, Wu FS, Jänne PA. A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 2015 May;26(5):894-901. Epub 2015 Feb 26. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01362296
- SELECT-1: Jänne PA, van den Heuvel MM, Barlesi F, Cobo M, Mazieres J, Crinò L, Orlov S, Blackhall F, Wolf J, Garrido P, Poltoratskiy A, Mariani G, Ghiorghiu D, Kilgour E, Smith P, Kohlmann A, Carlile DJ, Lawrence D, Bowen K, Vansteenkiste J. Selumetinib plus docetaxel compared with docetaxel alone and progression-free survival in patients with KRAS-mutant advanced non-small cell lung cancer: The SELECT-1 randomized clinical trial. JAMA. 2017 May 9;317(18):1844-1853. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01933932
- CodeBreak 200: NCT04303780
- KRYSTAL-12: NCT04685135
Sotorasib monotherapy
Regimen
| FDA-recommended dose |
| Study | Dates of enrollment | Evidence | |
|---|---|---|---|
Hong et al. 2020 (CodeBreaK100)
|
2018-2020 | Phase 1/2 (RT) |
Note: this is the dose used in the expansion cohort.
Biomarker eligibility criteria
- KRAS p.G12C mutation
References
- CodeBreaK100: Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, Bang YJ, Dy GK, Krauss JC, Kuboki Y, Kuo JC, Coveler AL, Park K, Kim TW, Barlesi F, Munster PN, Ramalingam SS, Burns TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G, Kim J, Houk BE, Canon J, Lipford JR, Friberg G, Lito P, Govindan R, Li BT. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep 24;383(13):1207-1217. Epub 2020 Sep 20. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03600883
- Update: Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V, Govindan R. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 Jun 24;384(25):2371-2381. Epub 2021 Jun 4. link to original article link to PMC article PubMed