Non-small cell lung cancer, KRAS-mutated

Section editor transclusions Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.

3 regimens on this page 3 variants on this page

Advanced or metastatic disease, subsequent lines of therapy

Docetaxel monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Blumenschein et al. 2015 (GSK 114653)	2011-2012	Randomized Phase II (C)	Trametinib	Did not meet primary endpoint of PFS
Jänne et al. 2017 (SELECT-1)	2013-2016	Phase III (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 medications

• Per JMEI: Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2 (3 days)
• Per Chem et al. 2006: Dexamethasone (Decadron) as follows:
  • 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

1. 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 verified protocol PubMed NCT01362296
2. 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 verified protocol link to PMC article PubMed NCT01933932
3. KRYSTAL-12: NCT04685135

Sotorasib monotherapy

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Regimen

FDA-recommended dose

Study	Years 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

Targeted therapy

• Sotorasib (Lumakras) 960 mg PO once per day

Continued indefinitely

References

1. 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 verified protocol PubMed NCT03600883
   1. 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 PubMed