Difference between revisions of "CNS carcinoma"

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m (Text replacement - "'''contains dosing details in abstract'''" to "'''dosing details in abstract have been reviewed by our editors'''")
 
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<span id="BackToTop"></span>
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! colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Section editor'''
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<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
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[[#top|Back to Top]]
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| style="background-color:#F0F0F0" |[[File:SeemaNagpal.jpg|frameless|upright=0.3|center]]
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</div>
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|<big>[[User:Seemanagpal|Seema Nagpal, MD]]<br>Stanford University<br>Palo Alto, CA</big>
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{{#lst:Editorial board transclusions|neuro}}
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|-
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This page has regimens and guidelines that are not specific to any one type of cancer. For disease-specific regimens and guidelines, please go to the following pages:
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|}
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*[[Breast cancer, CNS metastases]]
 +
*[[Non-small cell lung cancer, CNS metastases]]
 +
 
 
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{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Guidelines=
 
=Guidelines=
−
==[http://www.asco.org/ ASCO]==
+
'''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]==
−
*'''2018:''' Ramakrishna et al. [https://doi.org/10.1200/JCO.2018.79.2713 Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/29939840 PubMed]
+
*'''2022:''' Schiff et al. [https://doi.org/10.1200/jco.22.00333 Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline] [https://pubmed.ncbi.nlm.nih.gov/35561283 PubMed]
−
 
+
==ASCO/SNO/ASTRO==
−
===Older===
+
*'''2021:''' Vogelbaum et al. [https://doi.org/10.1200/JCO.21.02314 Treatment for Brain Metastases] [https://pubmed.ncbi.nlm.nih.gov/34932393 PubMed]
−
 
 
−
*'''2014:''' Ramakrishna et al. [https://doi.org/10.1200/JCO.2013.54.0955 Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline] [https://pubmed.ncbi.nlm.nih.gov/24799487 PubMed]
 
−
 
 
 
==EANO/ESMO==
 
==EANO/ESMO==
−
*'''2021:''' Le Rhun et al. [https://doi.org/10.1016/j.annonc.2021.07.016 EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours]
+
*'''2021:''' Le Rhun et al. [https://doi.org/10.1016/j.annonc.2021.07.016 EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours] [https://pubmed.ncbi.nlm.nih.gov/34364998 PubMed]
−
*'''2017:''' Le Rhun et al. [https://www.esmo.org/Guidelines/Neuro-Oncology/EANO-ESMO-Leptomeningeal-Metastasis-Clinical-Practice-Guidelines EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours]
+
*'''2017:''' Le Rhun et al. [https://www.esmo.org/Guidelines/Neuro-Oncology/EANO-ESMO-Leptomeningeal-Metastasis-Clinical-Practice-Guidelines EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours] [https://pubmed.ncbi.nlm.nih.gov/28881917 PubMed]
 +
==ISRS==
 +
*'''2022:''' Grishcuk et al. [https://doi.org/10.1016/j.prro.2022.10.013 ISRS Technical Guidelines for Stereotactic Radiosurgery: Treatment of Small Brain Metastases (≤1 cm in Diameter)] [https://pubmed.ncbi.nlm.nih.gov/36435388/ PubMed]
 +
*'''2018:''' Chao et al. [https://doi.org/10.1093/neuros/nyx522 Stereotactic Radiosurgery in the Management of Limited (1-4) Brain Metasteses: Systematic Review and International Stereotactic Radiosurgery Society Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/29126142/ PubMed]
  
−
==[https://www.nccn.org/ NCCN]==
+
==NCCN==
 +
*''NCCN does not have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425 NCCN Guidelines - Central Nervous System Cancers].''
  
−
*[https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf NCCN Guidelines - Central Nervous System Cancers]
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=All lines of therapy=
−
 
 
−
=Unselected all lines of therapy=
 
 
==Whole brain irradiation {{#subobject:6115dc|Regimen=1}}==
 
==Whole brain irradiation {{#subobject:6115dc|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
WBRT: '''<u>W</u>'''hole-'''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
WBRT: '''<u>W</u>'''hole-'''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:d377ed|Variant=1}}===
 
===Regimen {{#subobject:d377ed|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 20%"|Dates of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.redjournal.org/article/S0360-3016(07)04231-9/fulltext Knisely et al. 2007 (RTOG 0118)]
+
|[https://doi.org/10.1016/j.ijrobp.2007.09.016 Knisely et al. 2007 (RTOG 0118)]
 
|2002-2004
 
|2002-2004
−
| style="background-color:#1a9851" |Phase III (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|Thalidomide & WBRT
+
|[[#Thalidomide_.26_WBRT_999|Thalidomide & WBRT]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Radiotherapy====
 
====Radiotherapy====
−
 
+
*[[External_beam_radiotherapy|Whole-brain irradiation]] 250 cGy fractions x 15 (total dose: 3750 cGy)
−
*[[External_beam_radiotherapy|Whole-brain irradiation]] 2.5 Gy fractions x 15 (total dose: 37.5 Gy)
 
−
 
 
−
'''One course'''
 
−
 
 
−
===References===
 
−
 
 
−
#'''RTOG 0118:''' Knisely JP, Berkey B, Chakravarti A, Yung AW, Curran WJ Jr, Robins HI, Movsas B, Brachman DG, Henderson RH, Mehta MP. A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118). Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):79-86. Epub 2007 Dec 31. [https://www.redjournal.org/article/S0360-3016(07)04231-9/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/18164847 PubMed] NCT00033254
 
−
 
 
−
=Breast cancer, HER2-positive, all lines of therapy=
 
−
==Capecitabine & Lapatinib {{#subobject:800fde|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:653bef|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/JCO.2014.57.1794 Pivot et al. 2015 (CEREBEL)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 
−
|[[#Capecitabine_.26_Trastuzumab_.28XH.29|Capecitabine & Trastuzumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CNS metastases as first site of relapse
 
−
|-
 
−
|}
 
−
====Biomarker eligibility criteria====
 
−
 
 
−
*Gene: HER2 [[Biomarkers#Genes#Her2|Positive]]
 
−
*Clinical Trial Eligibility: score > 2.2 by fluorescence in situ hybridization and/or 3+ amplification by immunohistochemistry or chromogenic/silver in situ hybridization
 
−
 
 
−
====Chemotherapy====
 
−
 
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
====Targeted therapy====
 
−
*[[Lapatinib (Tykerb)]] 1250 mg PO once per day
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
 
 
−
#'''CEREBEL:''' Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2014.57.1794 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25605838 PubMed] NCT00820222
 
−
 
 
−
==Capecitabine & Trastuzumab (XH) {{#subobject:677608|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
XH: '''<u>X</u>'''eloda (Capecitabine) & '''<u>H</u>'''erceptin
 
−
===Regimen {{#subobject:e14cab|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/JCO.2014.57.1794 Pivot et al. 2015 (CEREBEL)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase III (C)
 
−
|[[#Capecitabine_.26_Lapatinib|Capecitabine & Lapatanib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CNS metastases as first site of relapse
 
−
|-
 
−
|}
 
−
 
 
−
====Biomarker eligibility criteria====
 
−
 
 
−
*Gene HER2 [[Biomarkers#Genes.23Her2|Positive]]
 
−
*Clinical Trial Eligibility: score > 2.2 by fluorescence in situ hybridization and/or 3+ amplification by immunohistochemistry or chromogenic/silver in situ hybridization
 
−
 
 
−
====Chemotherapy====
 
−
 
 
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
====Targeted therapy====
 
−
*[[Trastuzumab (Herceptin)]] as follows:
 
−
**Cycle 1: 8 mg/kg IV once on day 1
 
−
**Cycle 2 onwards: 6 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
 
 
−
#'''CEREBEL:''' Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2014.57.1794 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/25605838 PubMed] NCT00820222
 
−
 
 
−
==Capecitabine & Trastuzumab (XH) & Tucatinib {{#subobject:8d0gg5|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:771gcc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/nejmoa1914609 Murthy et al. 2019 (HER2CLIMB)]
 
−
|2016-2019
 
−
|style="background-color:#1a9851"|Phase III (E-RT-esc)
 
−
|[[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 21.9 vs 17.4 mo<br>(HR 0.66, 95% CI 0.50-0.88)
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
====Targeted therapy====
 
−
*[[Tucatinib (Tukysa)]] 300 mg PO twice per day
 
−
*[[Trastuzumab (Herceptin)]] as follows:
 
−
**Cycle 1: 8 mg/kg IV once on day 1
 
−
**Cycle 2 onwards: 6 mg/kg IV once on day 1
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
# '''HER2CLIMB:''' Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):597-609. Epub 2019 Dec 11. Erratum in: N Engl J Med. 2020 Feb 6;382(6):586. [https://doi.org/10.1056/nejmoa1914609 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/31825569 PubMed] NCT02614794
 
−
## '''Subgroup analysis:''' Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol. 2020 Aug 10;38(23):2610-2619. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00775 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403000/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32468955 PubMed]
 
−
 
 
−
=Non-small cell lung cancer, all lines of therapy=
 
−
==Dexamethasone monotherapy {{#subobject:adb3fe|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:6a5b0e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082599/ Mulvenna et al. 2016 (QUARTZ)]
 
−
| style="background-color:#1a9851" |Phase III (E-de-esc)
 
−
|[[#Dexamethasone_.26_WBRT|Dexamethasone & WBRT]]
 
−
|
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior QALYs
 
−
|-
 
−
|}
 
−
====Supportive therapy====
 
−
 
 
−
*[[Dexamethasone (Decadron)]]
 
−
 
 
−
===References===
 
−
 
 
−
#'''QUARTZ:''' Mulvenna P, Nankivell M, Barton R, Faivre-Finn C, Wilson P, McColl E, Moore B, Brisbane I, Ardron D, Holt T, Morgan S, Lee C, Waite K, Bayman N, Pugh C, Sydes B, Stephens R, Parmar MK, Langley RE. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016 Oct 22;388(10055):2004-2014. Epub 2016 Sep 4. [https://doi.org/10.1016/s0140-6736(16)30825-x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082599/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27604504 PubMed]
 
−
 
 
−
==Dexamethasone & WBRT {{#subobject:04a6d4|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:da6414|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082599/ Mulvenna et al. 2016 (QUARTZ)]
 
−
| style="background-color:#1a9851" |Phase III (C)
 
−
|[[#Dexamethasone_monotherapy|Dexamethasone]]
 
−
|
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior QALYs
 
−
|-
 
−
|}
 
−
====Radiotherapy====
 
−
 
 
−
*[[External beam radiotherapy|WBRT]], 20 Gy in 5 fractions
 
−
 
 
−
====Supportive medications====
 
−
 
 
−
*[[Dexamethasone (Decadron)]]
 
−
 
 
−
===References===
 
−
 
 
−
#'''QUARTZ:''' Mulvenna P, Nankivell M, Barton R, Faivre-Finn C, Wilson P, McColl E, Moore B, Brisbane I, Ardron D, Holt T, Morgan S, Lee C, Waite K, Bayman N, Pugh C, Sydes B, Stephens R, Parmar MK, Langley RE. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016 Oct 22;388(10055):2004-2014. Epub 2016 Sep 4. [https://doi.org/10.1016/s0140-6736(16)30825-x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082599/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27604504 PubMed]
 
−
 
 
−
==Teniposide & WBRT {{#subobject:04facd4|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:19bu14|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/JCO.2000.18.19.3400 Postmus et al. 2000]
 
−
|1989-1995
 
−
| style="background-color:#1a9851" |Phase III (E-esc)
 
−
|Teniposide
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Teniposide (Vumon)]]
 
−
 
 
−
====Radiotherapy====
 
−
 
 
−
*[[External beam radiotherapy|WBRT]], 30 Gy in 10 fractions
 
−
 
 
−
===References===
 
−
 
 
−
#Postmus PE, Haaxma-Reiche H, Smit EF, Groen HJ, Karnicka H, Lewinski T, van Meerbeeck J, Clerico M, Gregor A, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G; European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group. Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 2000 Oct 1;18(19):3400-8. [https://doi.org/10.1200/JCO.2000.18.19.3400 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11013281 PubMed]
 
−
 
 
−
==Whole brain irradiation {{#subobject:61gh5b|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
WBRT: '''<u>W</u>'''hole-'''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
−
===Regimen {{#subobject:d37jgd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/PMC8168818/ Yang et al. 2021 (ENTER)]
 
−
|2013-NR in abstract
 
−
| style="background-color:#1a9851" |Phase III (C)
 
−
|Erlotinib & WBRT
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of intracranial PFS
 
−
|-
 
−
|}
 
−
====Radiotherapy====
 
−
 
 
−
*[[External_beam_radiotherapy|Whole-brain irradiation]]
 
−
 
 
 
'''One course'''
 
'''One course'''
−
 
+
</div></div>
−
===References===
 
−
 
 
−
#'''ENTER:''' Yang Z, Zhang Y, Li R, Yisikandaer A, Ren B, Sun J, Li J, Chen L, Zhao R, Zhang J, Xia X, Liao Z, Carbone DP. Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial. Neuro Oncol. 2021 Jun 1;23(6):967-978. [https://doi.org/10.1093/neuonc/noaa281 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168818/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33331923/ PubMed] NCT01887795
 
−
 
 
−
=Non-small cell lung cancer, ALK-mutated, all lines of therapy=
 
−
==Alectinib monotherapy {{#subobject:b1194c|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen variant #1, 300 mg twice per day {{#subobject:9cef11|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext Hida et al. 2017 (J-ALEX)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 
−
|Crizotinib
 
−
| style="background-color:#1a9850" |Superior TTP<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported CNS efficacy is based on the 2018 update.''<br>
 
−
''This is the PMDA-approved dose in Japan.''
 
−
 
 
−
====Biomarker eligibility criteria====
 
−
 
 
−
*Gene [[Biomarkers#Genes#ALK|ALK]] positive
 
−
 
 
−
====Targeted therapy====
 
−
 
 
−
*[[Alectinib (Alecensa)]] 300 mg PO twice per day
 
−
 
 
−
'''Continued indefinitely'''
 
−
 
 
−
===Regimen variant #2, 600 mg twice per day {{#subobject:92a408|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.nejm.org/doi/full/10.1056/NEJMoa1704795 Peters et al. 2017 (ALEX)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 
−
|Crizotinib
 
−
| style="background-color:#1a9850" |Superior TTP<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported CNS efficacy is based on the 2018 update.''
 
−
 
 
−
====Biomarker eligibility criteria====
 
−
 
 
−
*Gene [[Biomarkers#Genes#ALK|ALK]] positive
 
−
 
 
−
====Targeted therapy====
 
−
 
 
−
*[[Alectinib (Alecensa)]] 600 mg PO twice per day
 
−
 
 
−
'''Continued indefinitely'''
 
−
 
 
−
===References===
 
−
 
 
−
#'''J-ALEX:''' Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Shukuya T, Nakagawa K, Mitsudomi T, Yamamoto N, Asakawa T, Asabe R, Tanaka T, Tamura T. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017 Jul 1;390(10089):29-39. Epub 2017 May 10. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext link to original article]'''contains protocol'''[https://pubmed.ncbi.nlm.nih.gov/28501140 PubMed] JapicCTI-132316
 
−
##'''Subgroup analysis:''' Nishio M, Nakagawa K, Mitsudomi T, Yamamoto N, Tanaka T, Kuriki H, Zeaiter A, Tamura T. Analysis of central nervous system efficacy in the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:37-40. Epub 2018 Apr 17. [https://doi.org/10.1016/j.lungcan.2018.04.015 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29858024 PubMed]
 
−
#'''ALEX:''' Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Pérol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. Epub 2017 Jun 6. [https://www.nejm.org/doi/full/10.1056/NEJMoa1704795 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28586279 PubMed] NCT02075840
 
−
##'''Subgroup analysis:''' Gadgeel S, Peters S, Mok T, Shaw AT, Kim DW, Ou SI, Pérol M, Wrona A, Novello S, Rosell R, Zeaiter A, Liu T, Nüesch E, Balas B, Camidge DR. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018 Nov 1;29(11):2214-2222. [https://doi.org/10.1093/annonc/mdy405 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290889/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30215676 PubMed]
 
−
 
 
−
==Ceritinib monotherapy {{#subobject:d35518|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:a93389|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ Shaw et al. 2014 (ASCEND-1)]
 
−
| style="background-color:#91cf61" |Phase I, >20 pts in this dosing cohort
 
−
|-
 
−
|}
 
−
''Note: CNS efficacy is based on the 2016 update.''
 
−
====Targeted therapy====
 
−
 
 
−
*[[Ceritinib (Zykadia)]] 750 mg PO once per day on an empty stomach
 
−
 
 
−
'''21-day cycles'''
 
−
 
 
−
===References===
 
−
 
 
−
#'''Phase I:''' Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. [https://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24670165 PubMed]
 
−
##'''Update:''' Kim DW, Mehra R, Tan DSW, Felip E, Chow LQM, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Sutradhar S, Li S, Szczudlo T, Yovine A, Shaw AT. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 2016 Apr;17(4):452-463. Epub 2016 Mar 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00614-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063047/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26973324 PubMed]
 
−
 
 
−
=Non-small cell lung cancer, EGFR-mutated, all lines of therapy=
 
−
==Afatinib monotherapy {{#subobject:1bf6db|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:130d4a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1200/jco.2012.44.2806 Sequist et al. 2013 (LUX-Lung 3)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Phase III (E-switch-ooc)
 
−
|[[Non-small_cell_lung_cancer#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup>
 
−
|-
 
−
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70604-1/fulltext Wu et al. 2014 (LUX-Lung 6)]
 
−
|2010-2011
 
−
| style="background-color:#1a9851" |Phase III (E-switch-ooc)
 
−
|[[Non-small cell lung cancer#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported CNS-specific efficacy is based on the 2016 subgroup analysis.''
 
−
 
 
−
====Biomarker eligibility criteria====
 
−
 
 
−
*Gene [[Biomarkers#Gene#EGFR|EGFR]] mutation (Leu858Arg, exon 19 deletions, or other)
 
−
 
 
−
====Targeted therapy====
 
−
 
 
−
*[[Afatinib (Gilotrif)]] 40 mg PO once per day, given 1 hour before eating food (LUX-Lung 2: "no food intake immediately before or after afatinib")
 
−
**In '''LUX-Lung 3''', patients could be increased to 50 mg PO once per day if they did not experience any grade 2 or higher rash, diarrhea, mucositis, or other drug-related adverse event.
 
−
 
 
−
'''Continued indefinitely'''
 
−
 
 
−
===References===
 
−
 
 
−
#'''LUX-Lung 3:''' Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. [https://doi.org/10.1200/jco.2012.44.2806 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23816960 PubMed] NCT00949650
 
−
##'''HRQoL analysis:''' Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. [https://doi.org/10.1200/jco.2012.46.1764 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23816967 PubMed]
 
−
##'''Pooled update:''' Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71173-8/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/25589191 PubMed]
 
−
##'''Pooled analysis:''' Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00026-1/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/26051236 PubMed]
 
−
##'''Subgroup analysis:''' Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. [http://www.jto.org/article/S1556-0864(15)00220-8/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/26823294 PubMed]
 
−
#'''LUX-Lung 6:''' Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70604-1/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/24439929 PubMed] NCT01121393
 
−
##'''Pooled update:''' Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71173-8/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/25589191 PubMed]
 
−
##'''Pooled analysis:''' Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00026-1/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/26051236 PubMed]
 
−
##'''Subgroup analysis:''' Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. [http://www.jto.org/article/S1556-0864(15)00220-8/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/26823294 PubMed]
 
−
 
 
−
==Icotinib monotherapy {{#subobject:9720a1|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:d7253b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30262-X/fulltext Yang et al. 2017 (BRAIN)]
 
−
|2012-2015
 
−
| style="background-color:#1a9851" |Phase III (E-switch-ooc)
 
−
|WB-XRT
 
−
| style="background-color:#91cf60" |Seems to have superior intracranial PFS
 
−
|-
 
−
|}
 
−
''Note: this drug is only approved in China.''
 
−
 
 
−
====Biomarker eligibility criteria====
 
−
 
 
−
* EGFR Mutation
 
−
* Clinical Trial Eligibility: EGFR Exon 19 deletion, EGFR exon 21 L858R, Uncommon EGFR mutations
 
−
 
 
−
====Targeted therapy====
 
−
 
 
−
*[[Icotinib (Conmana)]] 125 mg PO three times per day
 
−
 
 
−
'''Continued indefinitely'''
 
−
 
 
−
===References===
 
−
 
 
−
#'''BRAIN:''' Yang JJ, Zhou C, Huang Y, Feng J, Lu S, Song Y, Huang C, Wu G, Zhang L, Cheng Y, Hu C, Chen G, Zhang L, Liu X, Yan HH, Tan FL, Zhong W, Wu YL. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial. Lancet Respir Med. 2017 Sep;5(9):707-716. Epub 2017 Jul 19. [https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30262-X/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/28734822 PubMed] NCT01724801
 
−
 
 
−
==Osimertinib monotherapy {{#subobject:PYR2|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen variant #1, 80 mg/day {{#subobject:PYV2|Variant=1}}===
 
−
{| class="wikitable" 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%"|Years 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/10.1093/annonc/mdx820 Goss et al. 2018 (AURA extension)]
 
−
|2013-NR
 
−
| style="background-color:#91cf61" |Phase II
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1612674 Mok et al. 2016 (AURA3)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase III (E-switch-ooc)
 
−
|1. [[Non-small cell lung cancer#Carboplatin_.26_Pemetrexed_2|Carboplatin & Pemetrexed]]<br> 2. [[Non-small cell lung cancer#Cisplatin_.26_Pemetrexed_3|Cisplatin & Pemetrexed]]
 
−
| style="background-color:#91cf60" |Seems to have superior ORR<sup>1</sup>
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase III (E-switch-ic)
 
−
|1. [[Non-small cell lung cancer#Erlotinib_monotherapy|Erlotinib]]<br> 2. [[Non-small cell lung cancer#Gefitinib_monotherapy|Gefitinib]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<sup>2</sup>
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdx820 Goss et al. 2018 (AURA2)]
 
−
|2014-NR
 
−
| style="background-color:#91cf61" |Phase II
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/j.jtho.2021.07.026 Yamaguchi et al. 2021 (WJOG9116L)]
 
−
|2016-2019
 
−
| style="background-color:#91cf61" |Phase II
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy reported for AURA3 is based on the 2018 subgroup analysis.''<br>
 
−
''<sup>2</sup>Reported efficacy reported for FLAURA is based on the 2018 subgroup analysis.''<br>
 
−
''Patients enrolled in AURA3 had locally advanced or metastatic NSCLC with progression after first-line EGFR TKI therapy, and were required to have presence of an EGFR p.T790M mutation.''
 
−
 
 
−
====Biomarker eligibility criteria====
 
−
*AURA3: [[Biomarkers#EGFR|EGFR]] [[Biomarkers#T790M|T790M]]
 
−
*FLAURA: [[Biomarkers#EGFR|EGFR]] [[Biomarkers#Exon_19|exon 19]] [[Biomarkers#Deletion|deletion]] or [[Biomarkers#EGFR|EGFR]] [[Biomarkers#L858R|L858R]]
 
−
 
 
−
====Targeted therapy====
 
−
 
 
−
*[[Osimertinib (Tagrisso)]] 80 mg PO once per day
 
−
 
 
−
'''Continued indefinitely'''
 
−
 
 
−
===Regimen variant #2, 160 mg/day {{#subobject:ugaj9c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030895/ Yang et al. 2019 (BLOOM)]
 
−
|2015-2017
 
−
| style="background-color:#91cf61" |Phase I, >20 pts
 
−
|BICR- LM ORR (62%), DoR 15.2 months<br>
 
−
Investigator- LM ORR (41%), DoR 8.3 months
 
−
|-
 
−
|}
 
−
<blockquote>''Patients with leptomeningeal metastases (LMs) from EGFR-mutated (EGFRm) advanced non-small-cell lung cancer (NSCLC) whose disease had progressed on previous EGFR-TKI therapy. BICR- Blinded Independent Central Review, DoR- Duration of Response, ORR-Objective response rate''</blockquote>
 
−
====Biomarker eligibility criteria====
 
−
*[[Biomarkers#EGFR|EGFR]] [[Biomarkers#Exon_19|exon 19]] [[Biomarkers#Deletion|deletion]] or [[Biomarkers#EGFR|EGFR]] [[Biomarkers#L858R|L858R]]
 
−
====Targeted therapy====
 
−
*[[Osimertinib (Tagrisso)]] 160 mg PO once per day
 
−
 
 
−
'''Continued indefinitely'''
 
−
 
 
 
===References===
 
===References===
−
 
+
#'''RTOG 0118:''' Knisely JP, Berkey B, Chakravarti A, Yung AW, Curran WJ Jr, Robins HI, Movsas B, Brachman DG, Henderson RH, Mehta MP. A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118). Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):79-86. Epub 2007 Dec 31. [https://doi.org/10.1016/j.ijrobp.2007.09.016 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18164847/ PubMed] [https://clinicaltrials.gov/study/NCT00033254 NCT00033254]
−
#'''AURA3:''' Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. [https://www.nejm.org/doi/full/10.1056/NEJMoa1612674 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27959700 PubMed] NCT02151981
 
−
##'''Subgroup analysis:''' Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. [https://doi.org/10.1200/JCO.2018.77.9363 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30059262 PubMed]
 
−
#'''AURA extension; AURA2:''' Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crinò L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Jänne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. [https://doi.org/10.1093/annonc/mdx820 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29293889 PubMed] NCT01802632; NCT02094261
 
−
#'''FLAURA:''' Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. [https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/29151359 PubMed] NCT02296125
 
−
##'''Subgroup analysis:''' Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. [https://doi.org/10.1200/JCO.2018.78.3118 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30153097 PubMed]
 
−
#'''BLOOM:''' Yang JCH, Kim SW, Kim DW, Lee JS, Cho BC, Ahn JS, Lee DH, Kim TM, Goldman JW, Natale RB, Brown AP, Collins B, Chmielecki J, Vishwanathan K, Mendoza-Naranjo A, Ahn MJ. Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study. J Clin Oncol. 2020 Feb 20;38(6):538-547. Epub 2019 Dec 6. [https://doi.org/10.1200/jco.19.00457 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030895/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31809241 PubMed] NCT02228369
 
−
#'''WJOG9116L:''' Yamaguchi H, Wakuda K, Fukuda M, Kenmotsu H, Mukae H, Ito K, Chibana K, Inoue K, Miura S, Tanaka K, Ebi N, Suetsugu T, Harada T, Kirita K, Yokoyama T, Nakatani Y, Yoshimura K, Nakagawa K, Yamamoto N, Sugio K. A Phase II Study of Osimertinib for Radiotherapy-Naive Central Nervous System Metastasis From NSCLC: Results for the T790M Cohort of the OCEAN Study (LOGIK1603/WJOG9116L). J Thorac Oncol. 2021 Dec;16(12):2121-2132. Epub 2021 Aug 19. [https://doi.org/10.1016/j.jtho.2021.07.026 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/34419684/ PubMed] UMIN000024218
 
  
 
[[Category:CNS carcinoma regimens]]
 
[[Category:CNS carcinoma regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:CNS cancers]]
 
[[Category:CNS cancers]]

Latest revision as of 23:40, 15 July 2024

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Section editor
SeemaNagpal.jpg
 Seema Nagpal, MD
Stanford University
Palo Alto, CA, USA
LinkedIn

This page has regimens and guidelines that are not specific to any one type of cancer. For disease-specific regimens and guidelines, please go to the following pages:

1 regimens on this page
1 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

ASCO/SNO/ASTRO

EANO/ESMO

ISRS

NCCN

All lines of therapy

Whole brain irradiation

WBRT: Whole-Brain Radiation Therapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Knisely et al. 2007 (RTOG 0118) 2002-2004 Phase 3 (C) Thalidomide & WBRT Did not meet primary endpoint of OS

Radiotherapy

One course

References

  1. RTOG 0118: Knisely JP, Berkey B, Chakravarti A, Yung AW, Curran WJ Jr, Robins HI, Movsas B, Brachman DG, Henderson RH, Mehta MP. A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118). Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):79-86. Epub 2007 Dec 31. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00033254
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