Difference between revisions of "Non-small cell lung cancer, KRAS-mutated"

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|<big>[[User:Travisosterman|Travis Osterman, DO, MS]]<br>Vanderbilt University<br>Nashville, TN</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]][https://twitter.com/TravisOsterman TravisOsterman]<br>[https://www.linkedin.com/in/travis-osterman-1850b236/ LinkedIn]
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Note: these are regimens tested in biomarker-specific populations, please see the '''[[Non-small cell lung cancer|main NSCLC page]]''' for other regimens.
 
Note: these are regimens tested in biomarker-specific populations, please see the '''[[Non-small cell lung cancer|main NSCLC page]]''' for other regimens.
 
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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.'''
 +
==[https://www.asco.org/ ASCO]==
 +
*'''2022:''' Singh et al. [https://doi.org/10.1200/jco.22.00824 Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline] [https://www.ncbi.nlm.nih.gov/pubmed/35816666 PubMed]
 +
 +
==[https://www.esmo.org/ ESMO]==
 +
*'''2023:''' Hendriks et al. [https://doi.org/10.1016/j.annonc.2022.12.009 Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/36872130 PubMed]
 +
 +
==NCCN==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450 NCCN Guidelines - Non-Small Cell Lung Cancer].''
 +
 
=Advanced or metastatic disease, subsequent lines of therapy=
 
=Advanced or metastatic disease, subsequent lines of therapy=
−
==Docetaxel monotherapy {{#subobject:fd1716|Regimen=1}}==
+
==Adagrasib monotherapy {{#subobject:fgac16|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:15yvb6|Variant=1}}===
 +
{| class="wikitable sortable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2204619 Jänne et al. 2022 (KRYSTAL-1<sub>NSCLC</sub>)]
 +
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 +
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-367-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
 +
|-
 +
|} -->
 +
|2020-01 to 2020-12
 +
| style="background-color:#91cf61" |Phase 1/2 (RT)
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*KRAS p.G12C mutation
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Adagrasib (Krazati)]] 600 mg PO twice per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
#'''KRYSTAL-1<sub>NSCLC</sub>:''' 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. [https://doi.org/10.1056/nejmoa2204619 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35658005/ PubMed] [https://clinicaltrials.gov/study/NCT03785249 NCT03785249]
 +
 +
==Docetaxel monotherapy {{#subobject:fd1716|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:b495b6|Variant=1}}===
 
===Regimen {{#subobject:b495b6|Variant=1}}===
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Dates of enrollment
−
!style="width: 25%"|Comparator
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855243/ Blumenschein et al. 2015 (GSK 114653)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855243/ Blumenschein et al. 2015 (GSK 114653)]
−
|style="background-color:#1a9851"|Randomized Phase II (C)
+
|2011-2012
−
|Trametinib
+
|style="background-color:#1a9851"|Randomized Phase 2 (C)
 +
|[[#Trametinib_monotherapy_999|Trametinib]]
 
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 
|-
 
|-
−
|[http://jamanetwork.com/journals/jama/article-abstract/2625317 Jänne et al. 2017 (SELECT-1)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5815037/ Jänne et al. 2017 (SELECT-1)]
−
|style="background-color:#1a9851"|Phase III (C)
+
|2013-2016
−
|Docetaxel & Selumetinib
+
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Docetaxel_.26_Selumetinib_999|Docetaxel & Selumetinib]]
 
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(23)00221-0 de Langen et al. 2023 (CodeBreak 200)]
 +
|2020-06-04 to 2021-04-26
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Sotorasib_monotherapy|Sotorasib]]
 +
| style="background-color:#d73027" |Inferior PFS
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
 
+
====Supportive therapy====
−
====Supportive medications====
 
 
*Per JMEI: [[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2 (3 days)
 
*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'''
 
'''21-day cycles'''
−
 
+
</div></div>
 +
===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. [https://doi.org/10.1093/annonc/mdv072 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855243/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25722381/ PubMed] [https://clinicaltrials.gov/study/NCT01362296 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. [https://doi.org/10.1001/jama.2017.3438 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5815037/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28492898/ PubMed] [https://clinicaltrials.gov/study/NCT01933932 NCT01933932]
 +
#'''CodeBreak 200:''' de Langen AJ, Johnson ML, Mazieres J, Dingemans AC, Mountzios G, Pless M, Wolf J, Schuler M, Lena H, Skoulidis F, Yoneshima Y, Kim SW, Linardou H, Novello S, van der Wekken AJ, Chen Y, Peters S, Felip E, Solomon BJ, Ramalingam SS, Dooms C, Lindsay CR, Ferreira CG, Blais N, Obiozor CC, Wang Y, Mehta B, Varrieur T, Ngarmchamnanrith G, Stollenwerk B, Waterhouse D, Paz-Ares L. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS. Lancet. 2023 Mar 4;401(10378):733-746. Epub 2023 Feb 7. [https://doi.org/10.1016/S0140-6736(23)00221-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36764316/ PubMed] [https://clinicaltrials.gov/study/NCT04303780 NCT04303780]
 +
# '''KRYSTAL-12:''' [https://clinicaltrials.gov/study/NCT04685135 NCT04685135]
 +
==Sotorasib monotherapy {{#subobject:fih3b6|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1cjgg6|Variant=1}}===
 +
{| class="wikitable sortable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| 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/pmc7571518/ Hong et al. 2020 (CodeBreaK100<sub>NSCLC</sub>)]
 +
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 +
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-280-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 +
|-
 +
|} -->
 +
|2018-2020
 +
| style="background-color:#91cf61" |Phase 1/2 (RT)
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(23)00221-0 de Langen et al. 2023 (CodeBreak 200)]
 +
|2020-06-04 to 2021-04-26
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|[[#Docetaxel_monotherapy|Docetaxel]]
 +
| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 5.6 vs 4.5 mo<br>(HR 0.66, 95% CI 0.51-0.86)
 +
|-
 +
|}
 +
''Note: this was the dose used in the expansion cohort of CodeBreaK100.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*KRAS p.G12C mutation
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Sotorasib (Lumakras)]] 960 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 
===References===
 
===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. [https://academic.oup.com/annonc/article/26/5/894/218509 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855243/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25722381 PubMed]
+
#'''CodeBreaK100<sub>NSCLC</sub>:''' 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. [https://doi.org/10.1056/nejmoa1917239 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7571518/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32955176/ PubMed] [https://clinicaltrials.gov/study/NCT03600883 NCT03600883]
−
# '''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. [http://jamanetwork.com/journals/jama/article-abstract/2625317 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28492898 PubMed]
+
##'''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. [https://doi.org/10.1056/nejmoa2103695 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9116274/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34096690/ PubMed]
−
 
+
##'''Update:''' Dy GK, Govindan R, Velcheti V, Falchook GS, Italiano A, Wolf J, Sacher AG, Takahashi T, Ramalingam SS, Dooms C, Kim DW, Addeo A, Desai J, Schuler M, Tomasini P, Hong DS, Lito P, Tran Q, Jones S, Anderson A, Hindoyan A, Snyder W, Skoulidis F, Li BT. Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100. J Clin Oncol. 2023 Jun 20;41(18):3311-3317. Epub 2023 Apr 25. [https://doi.org/10.1200/jco.22.02524 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37098232/ PubMed]
 +
#'''CodeBreak 200:''' de Langen AJ, Johnson ML, Mazieres J, Dingemans AC, Mountzios G, Pless M, Wolf J, Schuler M, Lena H, Skoulidis F, Yoneshima Y, Kim SW, Linardou H, Novello S, van der Wekken AJ, Chen Y, Peters S, Felip E, Solomon BJ, Ramalingam SS, Dooms C, Lindsay CR, Ferreira CG, Blais N, Obiozor CC, Wang Y, Mehta B, Varrieur T, Ngarmchamnanrith G, Stollenwerk B, Waterhouse D, Paz-Ares L. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS. Lancet. 2023 Mar 4;401(10378):733-746. Epub 2023 Feb 7. [https://doi.org/10.1016/S0140-6736(23)00221-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36764316/ PubMed] [https://clinicaltrials.gov/study/NCT04303780 NCT04303780]
 
[[Category:Non-small cell lung cancer regimens]]
 
[[Category:Non-small cell lung cancer regimens]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Biomarker-specific pages]]
−
[[Category:Lung cancers]]
+
[[Category:Non-small cell lung cancers]]

Latest revision as of 21:20, 29 June 2024

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Page editor Section editor
Singhi Eric.jpeg
 Eric K. Singhi, MD
MD Anderson Cancer Center
Houston, TX, USA
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 Amit Kulkarni, MBBS
University of Minnesota
Minneapolis, MN, USA
LinkedIn

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


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.

ASCO

ESMO

NCCN

Advanced or metastatic disease, subsequent lines of therapy

Adagrasib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Jänne et al. 2022 (KRYSTAL-1NSCLC) 2020-01 to 2020-12 Phase 1/2 (RT)

Biomarker eligibility criteria

  • KRAS p.G12C mutation

Targeted therapy

Continued indefinitely

References

  1. KRYSTAL-1NSCLC: 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
de Langen et al. 2023 (CodeBreak 200) 2020-06-04 to 2021-04-26 Phase 3 (C) Sotorasib Inferior PFS

Chemotherapy

Supportive therapy

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 dosing details in manuscript 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 dosing details in manuscript link to PMC article PubMed NCT01933932
  3. CodeBreak 200: de Langen AJ, Johnson ML, Mazieres J, Dingemans AC, Mountzios G, Pless M, Wolf J, Schuler M, Lena H, Skoulidis F, Yoneshima Y, Kim SW, Linardou H, Novello S, van der Wekken AJ, Chen Y, Peters S, Felip E, Solomon BJ, Ramalingam SS, Dooms C, Lindsay CR, Ferreira CG, Blais N, Obiozor CC, Wang Y, Mehta B, Varrieur T, Ngarmchamnanrith G, Stollenwerk B, Waterhouse D, Paz-Ares L. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS. Lancet. 2023 Mar 4;401(10378):733-746. Epub 2023 Feb 7. link to original article contains dosing details in abstract PubMed NCT04303780
  4. KRYSTAL-12: NCT04685135

Sotorasib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hong et al. 2020 (CodeBreaK100NSCLC) 2018-2020 Phase 1/2 (RT)
de Langen et al. 2023 (CodeBreak 200) 2020-06-04 to 2021-04-26 Phase 3 (E-switch-ooc) Docetaxel Superior PFS (primary endpoint)
Median PFS: 5.6 vs 4.5 mo
(HR 0.66, 95% CI 0.51-0.86)

Note: this was the dose used in the expansion cohort of CodeBreaK100.

Biomarker eligibility criteria

  • KRAS p.G12C mutation

Targeted therapy

Continued indefinitely

References

  1. CodeBreaK100NSCLC: 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
    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 link to PMC article PubMed
    2. Update: Dy GK, Govindan R, Velcheti V, Falchook GS, Italiano A, Wolf J, Sacher AG, Takahashi T, Ramalingam SS, Dooms C, Kim DW, Addeo A, Desai J, Schuler M, Tomasini P, Hong DS, Lito P, Tran Q, Jones S, Anderson A, Hindoyan A, Snyder W, Skoulidis F, Li BT. Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100. J Clin Oncol. 2023 Jun 20;41(18):3311-3317. Epub 2023 Apr 25. link to original article PubMed
  2. CodeBreak 200: de Langen AJ, Johnson ML, Mazieres J, Dingemans AC, Mountzios G, Pless M, Wolf J, Schuler M, Lena H, Skoulidis F, Yoneshima Y, Kim SW, Linardou H, Novello S, van der Wekken AJ, Chen Y, Peters S, Felip E, Solomon BJ, Ramalingam SS, Dooms C, Lindsay CR, Ferreira CG, Blais N, Obiozor CC, Wang Y, Mehta B, Varrieur T, Ngarmchamnanrith G, Stollenwerk B, Waterhouse D, Paz-Ares L. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS. Lancet. 2023 Mar 4;401(10378):733-746. Epub 2023 Feb 7. link to original article contains dosing details in abstract PubMed NCT04303780
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