Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
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{{#lst:Section editor transclusions|breast}}
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{| class="wikitable" style="text-align:center; width:100%;"
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! colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26" |'''Section editor'''
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! colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26" |'''Section editor'''
 +
|-
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| style="background-color:#F0F0F0; width:15%" |[[File:MartinSchoen.jpg|frameless|upright=0.3|center]]
 +
| style="width:35%" |<big>[[User:Marteens|Martin W. Schoen, MD, MPH]]<br>Saint Louis University<br>St. Louis, MO</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/mwschoen mwschoen]
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|style="background-color:#F0F0F0; width:15%"|[[File:Bdholaria.jpg|frameless|upright=0.3|center]]
 +
| style="width:35%" |<big>[[User:Bdholaria|Bhagirathbhai Dholaria, MBBS]]<br>Vanderbilt University<br>Nashville, TN</big>
 +
|-
 +
|}
 +
<big>Note that many of the regimens used to treat this disease are generic to '''[[B-cell acute lymphoblastic leukemia]]'''; this page contains regimens that are specific to T-cell acute lymphoblastic leukemia (a.k.a. T-cell lymphoblastic lymphoma when primarily nodal-based).</big>
 +
<big>'''Note: certain regimens have been moved to dedicated pages:
 +
*'''[[T-cell acute lymphoblastic leukemia, pediatric|Pediatric T-cell ALL]]
 +
</big>
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
|}
 
|}
−
<big>'''Note: this page has regimens which are specific to breast cancer that is BRCA-mutated. Please see the [[Breast cancer|main breast cancer]] page for other chemotherapy regimens.'''</big>
 
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Guidelines=
 
=Guidelines=
−
==[http://www.asc.org/ ASCO]==
+
=="How I Treat"==
−
*'''2021:''' Tung et al. [https://doi.org/10.1200/jco.21.01532 Adjuvant PARP Inhibitors in Patients With High-Risk Early-Stage HER2-Negative Breast Cancer and Germline BRCA Mutations: ASCO Hereditary Breast Cancer Guideline Rapid Recommendation Update]
+
*'''2020:''' Aldoss I, Douer D. How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood. 2020 Mar 26;135(13):987-995. [https://doi.org/10.1182/blood.2019002477 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31977001 PubMed]
−
==[http://www.esmo.org/ ESMO]==
+
==[https://www.nccn.org/ NCCN]==
−
*'''2011:''' Balmaña et al. [https://doi.org/10.1093/annonc/mdr373 BRCA in breast cancer: ESMO Clinical Practice Guidelines]
+
*[https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf NCCN Guidelines - T-cell Lymphomas]
−
=Adjuvant therapy=
+
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_all.pdf NCCN Guidelines - Pediatric Acute Lymphoblastic Leukemia]
−
==Olaparib monotherapy {{#subobject:56hxcd|Regimen=1}}==
+
=Pre-phase=
 +
==Prednisone monotherapy {{#subobject:30c275|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:3b0yga|Variant=1}}===
+
===Regimen {{#subobject:af8a3d|Variant=1}}===
−
{| class="wikitable" style="color:white; background-color:#404040"
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
|<small>'''FDA-recommended dose'''</small>
+
!style="width: 25%"|Study
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|}
+
|[https://doi.org/10.1200/JCO.2015.61.5385 Lepretre et al. 2015 (GRAALL-LYSA LL03)]
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
|style="background-color:#91cf61"|Phase 2
−
!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/nejmoa2105215 Tutt et al. 2021 (OlympiA)]
 
−
|2014-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
|style="background-color:#1a9850"|Superior invasive DFS<br>IDFS36: 86% vs 77%<br>(HR 0.58, 99.5% CI 0.41-0.82)
 
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#cbd5e8">
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Preceding treatment====
+
====Glucocorticoid therapy====
−
*[[Surgery#Breast_cancer_surgery|Primary local treatment]] +/- (neo-)adjuvant therapy
+
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days -7 to -1
 +
====CNS therapy, prophylaxis====
 +
*[[Methotrexate (MTX)]] 15 mg IT once at some point between days -7 and -4
 +
'''7-day course'''
 
</div>
 
</div>
−
<div class="toccolours" style="background-color:#b3e2cd">
+
<div class="toccolours" style="background-color:#cbd5e7">
−
====Targeted therapy====
+
====Subsequent treatment====
−
*[[Olaparib (Lynparza)]] 300 mg PO twice per day
+
*[[#Cyclophosphamide.2C_Daunorubicin.2C_L-Asparaginase.2C_Vincristine.2C_Prednisone|Cyclophosphamide, daunorubicin, L-asparaginase, vincristine, prednisone]] re-induction
−
'''28-day cycle for 13 cycles (1 year)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''OlympiA:''' Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, Gelber RD, de Azambuja E, Fielding A, Balmaña J, Domchek SM, Gelmon KA, Hollingsworth SJ, Korde LA, Linderholm B, Bandos H, Senkus E, Suga JM, Shao Z, Pippas AW, Nowecki Z, Huzarski T, Ganz PA, Lucas PC, Baker N, Loibl S, McConnell R, Piccart M, Schmutzler R, Steger GG, Costantino JP, Arahmani A, Wolmark N, McFadden E, Karantza V, Lakhani SR, Yothers G, Campbell C, Geyer CE Jr; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021 Jun 24;384(25):2394-2405. Epub 2021 Jun 3. [https://doi.org/10.1056/nejmoa2105215 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34081848/ PubMed] NCT02032823
+
<!-- Presented at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
−
=Advanced or metastatic disease, subsequent lines of therapy=
+
#'''GRAALL-LYSA LL03:''' Lepretre S, Touzart A, Vermeulin T, Picquenot JM, Tanguy-Schmidt A, Salles G, Lamy T, Béné MC, Raffoux E, Huguet F, Chevallier P, Bologna S, Bouabdallah R, Benichou J, Brière J, Moreau A, Tallon-Simon V, Seris S, Graux C, Asnafi V, Ifrah N, Macintyre E, Dombret H. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study. J Clin Oncol. 2016 Feb 20;34(6):572-80. Epub 2015 Dec 7. [https://doi.org/10.1200/JCO.2015.61.5385 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.61.5385 link to data supplement] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26644537 PubMed] NCT00195871
−
==Capecitabine monotherapy {{#subobject:842c42|Regimen=1}}==
+
=Upfront induction therapy=
 +
==Cyclophosphamide, Daunorubicin, L-Asparaginase, Vincristine, Prednisone {{#subobject:b90dc3|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:fb2810|Variant=1}}===
+
===Regimen, "Pediatric-like GRAALL reinforced induction" {{#subobject:56ea06|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 20%"|Study
+
!style="width: 25%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!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/NEJMoa1802905 Litton et al. 2018 (EMBRACA)]
+
|[https://doi.org/10.1200/JCO.2015.61.5385 Lepretre et al. 2015 (GRAALL-LYSA LL03)]
−
|2013-2017
+
|style="background-color:#91cf61"|Phase 2
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Talazoparib_monotherapy|Talazoparib]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Olaparib_monotherapy_2|Olaparib]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#fdcdac">
+
''Note: This regimen was meant for patients less than 60 years old (up to age 59). Regimen is as per the [[Acute_lymphocytic_leukemia#Pediatric-like_GRAALL_induction|GRAALL-2003 Study]] with some minor differences. High-risk patients with an HLA sibling-matched donor or a fully matched (10/10) unrelated donor who achieved CR1 were offered allogeneic stem cell transplant.''
−
====Biomarker eligibility criteria====
+
<div class="toccolours" style="background-color:#cbd5e8">
−
*EMBRACA: Germline BRCA1 or BRCA2 mutation
+
====Preceding treatment====
−
*OlympiAD: Confirmed deleterious or suspected deleterious germline BRCA mutation
+
*[[#Prednisone_monotherapy|Prednisone pre-phase]]
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 3 hours once on day 1, then 500 mg/m<sup>2</sup> IV every 12 hours on days 15 & 16
−
'''21-day cycles'''
+
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3, then 30 mg/m<sup>2</sup> IV once per day on days 15 & 16
−
</div></div>
+
*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup>/day (route not specified) on days 8, 10, 12, 20, 22, 24, 26, 28
−
===References===
+
*[[Vincristine (Oncovin)]] 2 mg IV once per day on days 1, 8, 15, 22
−
# '''OlympiAD:''' Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [https://doi.org/10.1056/NEJMoa1706450 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28578601 PubMed] NCT02000622
+
====Glucocorticoid therapy====
−
## '''Update:''' Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. [https://doi.org/10.1093/annonc/mdz012 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503629/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30689707 PubMed]
+
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 14
−
# '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
+
====Supportive therapy====
−
## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
+
*[[Lenograstim (Granocyte)]] 150 mcg/m<sup>2</sup> SC once per day from day 17 until myeloid recovery
−
==Carboplatin monotherapy {{#subobject:16h4a8|Regimen=1}}==
+
====CNS therapy, prophylaxis====
−
<div class="toccolours" style="background-color:#eeeeee">
+
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 1 & 8
−
===Regimen {{#subobject:ujsx06|Variant=1}}===
+
*[[Cytarabine (Ara-C)]] 40 mg IT once per day on days 1 & 8
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
*[[Methylprednisolone (Solumedrol)|Methylprednisolone (Depo-Medrol)]] 40 mg IT once per day on days 1 & 8
−
!style="width: 20%"|Study
+
'''28-day course'''
−
!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/PMC6372067/ Tutt et al. 2018 (TNT)]
 
−
|2008-2014
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#Docetaxel_monotherapy|Docetaxel]]
 
−
| style="background-color:#1a9850" |Superior ORR<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on subgroup analysis.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''TNT:''' Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. Epub 2018 Apr 30. [https://www.nature.com/articles/s41591-018-0009-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372067/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29713086 PubMed] NCT00532727
 
−
==Carboplatin & Paclitaxel (CP) {{#subobject:842252|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f16cn0|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/10.1016/s1470-2045(20)30447-2 Diéras et al. 2020 (BROCADE3)]
 
−
|2014-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Veliparib_88|CP & Veliparib]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*Confirmed deleterious germline BRCA1 or BRCA2 mutation
 
 
</div>
 
</div>
−
<div class="toccolours" style="background-color:#b3e2cd">
+
<div class="toccolours" style="background-color:#cbd5e7">
−
====Chemotherapy====
+
====Subsequent treatment====
−
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+
*See paper for details beyond induction
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
'''21-day cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
#'''BROCADE3:''' Diéras V, Han HS, Kaufman B, Wildiers H, Friedlander M, Ayoub JP, Puhalla SL, Bondarenko I, Campone M, Jakobsen EH, Jalving M, Oprean C, Palácová M, Park YH, Shparyk Y, Yañez E, Khandelwal N, Kundu MG, Dudley M, Ratajczak CK, Maag D, Arun BK. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Oct;21(10):1269-1282. Epub 2020 Aug 27. [https://doi.org/10.1016/s1470-2045(20)30447-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32861273 PubMed] NCT02163694
+
<!-- Presented at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
−
==Docetaxel monotherapy {{#subobject:3e34a8|Regimen=1}}==
+
#'''GRAALL-LYSA LL03:''' Lepretre S, Touzart A, Vermeulin T, Picquenot JM, Tanguy-Schmidt A, Salles G, Lamy T, Béné MC, Raffoux E, Huguet F, Chevallier P, Bologna S, Bouabdallah R, Benichou J, Brière J, Moreau A, Tallon-Simon V, Seris S, Graux C, Asnafi V, Ifrah N, Macintyre E, Dombret H. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study. J Clin Oncol. 2016 Feb 20;34(6):572-80. Epub 2015 Dec 7. [https://doi.org/10.1200/JCO.2015.61.5385 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.61.5385 link to data supplement] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26644537 PubMed] NCT00195871
 +
==Daunorubicin, Pegaspargase, Vincristine, Dexamethasone {{#subobject:516f7b|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:71bf06|Variant=1}}===
+
===Regimen, modified ABFM {{#subobject:88f520|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 20%"|Study
+
!style="width: 50%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!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/PMC6372067/ Tutt et al. 2018 (TNT)]
+
|[https://doi.org/10.1016/S1470-2045(12)70600-9 Vora et al. 2013 (UKALL 2003)]
−
|2008-2014
+
| style="background-color:#91cf61" |Non-randomized portion of RCT
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Carboplatin_monotherapy|Carboplatin]]
 
−
| style="background-color:#d73027" |Inferior ORR<sup>1</sup>
 
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>Reported efficacy is based on subgroup analysis.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
+
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 8, 15, 22
−
'''21-day cycle for 6 to 8 cycles'''
+
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once per day on days 4 & 18
−
</div></div>
+
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22
−
===References===
+
====Glucocorticoid therapy====
−
# '''TNT:''' Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. Epub 2018 Apr 30. [https://www.nature.com/articles/s41591-018-0009-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372067/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29713086 PubMed] NCT00532727
+
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 28
−
==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}==
+
====CNS therapy, prophylaxis====
−
<div class="toccolours" style="background-color:#eeeeee">
+
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
−
===Regimen {{#subobject:25ef0|Variant=1}}===
+
**Ages 1 to 1.99: 30 mg IT once on day 1
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
**Ages 2 to 2.99: 50 mg IT once on day 1
−
!style="width: 20%"|Study
+
**Age 3 and older: 70 mg IT once on day 1
−
!style="width: 20%"|Years of enrollment
+
*[[Methotrexate (MTX)]] by the following age-based criteria:
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29
−
!style="width: 20%"|Comparator
+
**Ages 2 to 2.99: 10 mg IT once per day on days 8 & 29
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
**Ages 3 to 8.99: 12 mg IT once per day on days 8 & 29
−
|-
+
**Age 9 and older: 15 mg IT once per day on days 8 & 29
−
|[https://doi.org/10.1056/NEJMoa1802905 Litton et al. 2018 (EMBRACA)]
+
'''4-week course'''
−
|2013-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Talazoparib_monotherapy|Talazoparib]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Olaparib_monotherapy_2|Olaparib]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*EMBRACA: Germline BRCA1 or BRCA2 mutation
 
−
*OlympiAD: Confirmed deleterious or suspected deleterious germline BRCA mutation
 
 
</div>
 
</div>
−
<div class="toccolours" style="background-color:#b3e2cd">
+
<div class="toccolours" style="background-color:#cbd5e7">
−
====Chemotherapy====
+
====Subsequent treatment====
−
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV over 2 to 5 minutes once per day on days 1 & 8
+
*[[#Cyclophosphamide.2C_Cytarabine.2C_Mercaptopurine.2C_Pegaspargase.2C_Vincristine|Cyclophosphamide, cytarabine, mercaptopurine, pegaspargase, vincristine]] consolidation
−
'''21-day cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''OlympiAD:''' Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [https://doi.org/10.1056/NEJMoa1706450 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28578601 PubMed] NCT02000622
+
# '''UKALL 2003:''' Vora A, Goulden N, Wade R, Mitchell C, Hancock J, Hough R, Rowntree C, Richards S. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013 Mar;14(3):199-209. [https://doi.org/10.1016/S1470-2045(12)70600-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23395119 PubMed] ISRCTN07355119
−
## '''Update:''' Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. [https://doi.org/10.1093/annonc/mdz012 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503629/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30689707 PubMed]
+
=Consolidation after upfront therapy=
−
# '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
+
==Etoposide & TBI, then allo HSCT {{#subobject:b389e1|Regimen=1}}==
−
## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
 
−
==Gemcitabine monotherapy {{#subobject:af0915|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:11b425|Variant=1}}===
+
===Regimen {{#subobject:e4216b|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 20%"|Study
+
!style="width: 25%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!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/NEJMoa1802905 Litton et al. 2018 (EMBRACA)]
+
|[http://www.bloodjournal.org/content/106/12/3760.long Rowe et al. 2005 (MRC UKALL XII/ECOG E2993)]
−
|2013-2017
+
| style="background-color:#91cf61" |Non-randomized portion of RCT
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Talazoparib_monotherapy|Talazoparib]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#fdcdac">
+
{{#lst:Allogeneic HSCT|e4216b}}
−
====Biomarker eligibility criteria====
+
====Immunotherapy====
−
*Germline BRCA1 or BRCA2 mutation
+
*[[Allogeneic stem cells]]
−
</div>
+
'''Stem cells transfused on day 0'''
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
 
−
## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
 
−
==Olaparib monotherapy {{#subobject:a019cd|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 100 mg twice per day {{#subobject:31ed8c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)60892-6 Tutt et al. 2010 (KU36-44)]
 
−
|2007-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Olaparib (Lynparza)]] 100 mg PO twice per day
 
−
'''Continued indefinitely'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 300 mg twice per day {{#subobject:3b0774|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%"|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/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
−
|2014-2015
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
 
−
|1a. [[#Capecitabine_monotherapy|Capecitabine]]<br>1b. [[#Eribulin_monotherapy|Eribulin]]<br>1c. [[#Vinorelbine_monotherapy|Vinorelbine]]
 
−
|style="background-color:#1a9850"|Superior PFS <br>Median PFS: 7.0 mo vs 4.2 mo <br>(HR 0.58, 95% CI 0.43-0.80)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*Confirmed deleterious or suspected deleterious germline BRCA mutation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Olaparib (Lynparza)]] 300 mg PO twice per day
 
−
'''Continued indefinitely'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 400 mg twice per day {{#subobject:31cf8c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)60892-6 Tutt et al. 2010 (KU36-44)]
 
−
|2007-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ Kaufman et al. 2014 (Study 42)]
 
−
|2010-NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: Patients in Study 42 had germline BRCA1/2 mutations and had progressed after at least three lines of treatment for metastatic disease.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Olaparib (Lynparza)]] 400 mg PO twice per day
 
−
'''Continued indefinitely'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''KU36-44:''' Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):235-44. Epub 2010 Jul 6. [https://doi.org/10.1016/S0140-6736(10)60892-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20609467 PubMed] NCT00494234
+
# '''MRC UKALL XII/ECOG E2993:''' Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. [http://www.bloodjournal.org/content/106/12/3760.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16105981 PubMed] NCT00002514
−
<!-- Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. -->
+
## '''Update:''' Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. [http://www.bloodjournal.org/content/111/4/1827.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/18048644 PubMed]  
−
# '''Study 42:''' Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. [https://doi.org/10.1200/jco.2014.56.2728 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25366685 PubMed] NCT01078662
+
## '''Update:''' Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. [http://www.bloodjournal.org/content/113/19/4489.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188540/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19244158 PubMed]  
−
# '''OlympiAD:''' Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [https://doi.org/10.1056/NEJMoa1706450 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28578601 PubMed] NCT02000622
+
## '''Update:''' Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. [http://www.bloodjournal.org/content/123/6/843.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916877/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24277073 PubMed]
−
## '''Update:''' Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. [https://doi.org/10.1093/annonc/mdz012 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503629/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30689707 PubMed]
+
=Relapsed or refractory=
−
 
+
==Nelarabine monotherapy {{#subobject:bb7a38|Regimen=1}}==
−
==Talazoparib monotherapy {{#subobject:bb55eb|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:06a5b4|Variant=1}}===
+
===Regimen variant #1, 5-day dosing {{#subobject:44a025|Variant=1}}===
−
{| class="wikitable" style="color:white; background-color:#404040"
+
{| class="wikitable sortable" style="width: 80%; text-align:center;"
−
|<small>'''FDA-recommended dose'''</small>
+
!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://doi.org/10.1200/JCO.2005.03.426 Berg et al. 2005]
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
|1997-2002
−
!style="width: 20%"|Study
+
|style="background-color:#91cf61"|Phase 2 (RT)
−
!style="width: 20%"|Years of enrollment
+
|ORR: 14-55%
−
!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/NEJMoa1802905 Litton et al. 2018 (EMBRACA)]
+
|[https://doi.org/10.1111/bjh.14874 Zwaan et al. 2017 (GSK 111081)]
−
|2013-2017
+
|2009-2014
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
+
|style="background-color:#91cf61"|Phase 4
−
|Physician's choice of:<br>1a. [[#Capecitabine_monotherapy|Capecitabine]]<br>1b. [[#Eribulin_monotherapy|Eribulin]]<br>1c. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>1d. [[#Vinorelbine_monotherapy|Vinorelbine]]
+
|style="background-color:#666666; color:white"|ORR: 39%
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 8.6 vs 5.6 mo<br>(HR 0.54, 95% CI 0.41-0.71)
 
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*Germline BRCA1 or BRCA2 mutation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Talazoparib (Talzenna)]] 1 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
 
−
## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
 
−
==Vinorelbine monotherapy {{#subobject:5c104c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 2 out of 3 weeks {{#subobject:7321fd|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/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Olaparib_monotherapy_2|Olaparib]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*Confirmed deleterious or suspected deleterious germline BRCA mutation
 
−
</div>
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
+
*[[Nelarabine (Arranon)]] 650 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
'''21-day cycles'''
 
'''21-day cycles'''
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, weekly {{#subobject:bjab1fd|Variant=1}}===
+
===Regimen variant #2, intermittent dosing {{#subobject:b5ce00|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
−
!style="width: 20%"|Study
+
!style="width: 25%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 25%"|Years of enrollment
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|Comparator
+
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJMoa1802905 Litton et al. 2018 (EMBRACA)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1941786/ DeAngelo et al. 2007 (CALGB 19801)]
−
|2013-2017
+
|1998-2001
−
| style="background-color:#1a9851" |Phase 3 (C)
+
|style="background-color:#91cf61"|Phase 2 (RT)
−
|[[#Talazoparib_monotherapy|Talazoparib]]
+
|style="background-color:#666666; color:white"|ORR: 41% (95% CI, 15-43)
−
| style="background-color:#d73027" |Inferior PFS
 
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#fdcdac">
+
''See paper for details about the schedule.''
−
====Biomarker eligibility criteria====
 
−
*Germline BRCA1 or BRCA2 mutation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV over 6 to 10 minutes once per day on days 1, 8, 15
+
*[[Nelarabine (Arranon)]] 1500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 3, 5
−
'''21-day cycles'''
+
'''21-day cycle for 3 to 4 cycles (or delayed for count recovery)'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''OlympiAD:''' Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [https://doi.org/10.1056/NEJMoa1706450 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28578601 PubMed] NCT02000622
+
# Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, Billett A, Kurtzberg J, Reaman G, Gaynon P, Whitlock J, Krailo M, Harris MB; Children's Oncology Group. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol. 2005 May 20;23(15):3376-82. [https://doi.org/10.1200/JCO.2005.03.426 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15908649 PubMed]
−
## '''Update:''' Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. [https://doi.org/10.1093/annonc/mdz012 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503629/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30689707 PubMed]
+
# '''CALGB 19801:''' DeAngelo DJ, Yu D, Johnson JL, Coutre SE, Stone RM, Stopeck AT, Gockerman JP, Mitchell BS, Appelbaum FR, Larson RA. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007 Jun 15;109(12):5136-42. Epub 2007 Mar 7. [http://www.bloodjournal.org/content/109/12/5136.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1941786/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17344466 PubMed]
−
# '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
+
# '''GSK 111081:''' Zwaan CM, Kowalczyk J, Schmitt C, Bielorai B, Russo MW, Woessner M, Ranganathan S, Leverger G. Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study. Br J Haematol. 2017 Oct;179(2):284-293. Epub 2017 Aug 2. [https://doi.org/10.1111/bjh.14874 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28771663 PubMed] NCT00866671
−
## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
+
[[Category:T-cell acute lymphoblastic leukemia regimens]]
−
=Additional resources=
+
[[Category:Disease-specific pages]]
−
*[[Breast cancer BRCA1 & BRCA2 genetic testing]]
+
[[Category:Acute lymphoblastic leukemias]]
−
*[https://oncomx.org/searchview/?gene=BRCA1 OncoMX -- BRCA1]
+
[[Category:T-cell leukemias]]
−
*[https://oncomx.org/searchview/?gene=BRCA2 OncoMX -- BRCA2]
 
−
[[Category:Breast cancer regimens]]
 
−
[[Category:Biomarker-specific pages]]
 
−
[[Category:Malignant breast neoplasm]]
 

Revision as of 20:25, 22 October 2022

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Section editor Section editor
MartinSchoen.jpg
 Martin W. Schoen, MD, MPH
Saint Louis University
St. Louis, MO
Social-twitter-icon.png mwschoen
Bdholaria.jpg
 Bhagirathbhai Dholaria, MBBS
Vanderbilt University
Nashville, TN

Note that many of the regimens used to treat this disease are generic to B-cell acute lymphoblastic leukemia; this page contains regimens that are specific to T-cell acute lymphoblastic leukemia (a.k.a. T-cell lymphoblastic lymphoma when primarily nodal-based). Note: certain regimens have been moved to dedicated pages:

0 regimens on this page
0 variants on this page


Guidelines

"How I Treat"

  • 2020: Aldoss I, Douer D. How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood. 2020 Mar 26;135(13):987-995. link to original article PubMed

NCCN

Pre-phase

Prednisone monotherapy

Regimen

Study Evidence
Lepretre et al. 2015 (GRAALL-LYSA LL03) Phase 2

Glucocorticoid therapy

CNS therapy, prophylaxis

7-day course

Subsequent treatment

References

  1. GRAALL-LYSA LL03: Lepretre S, Touzart A, Vermeulin T, Picquenot JM, Tanguy-Schmidt A, Salles G, Lamy T, Béné MC, Raffoux E, Huguet F, Chevallier P, Bologna S, Bouabdallah R, Benichou J, Brière J, Moreau A, Tallon-Simon V, Seris S, Graux C, Asnafi V, Ifrah N, Macintyre E, Dombret H. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study. J Clin Oncol. 2016 Feb 20;34(6):572-80. Epub 2015 Dec 7. link to original article link to data supplement contains dosing details in abstract PubMed NCT00195871

Upfront induction therapy

Cyclophosphamide, Daunorubicin, L-Asparaginase, Vincristine, Prednisone

Regimen, "Pediatric-like GRAALL reinforced induction"

Study Evidence
Lepretre et al. 2015 (GRAALL-LYSA LL03) Phase 2

Note: This regimen was meant for patients less than 60 years old (up to age 59). Regimen is as per the GRAALL-2003 Study with some minor differences. High-risk patients with an HLA sibling-matched donor or a fully matched (10/10) unrelated donor who achieved CR1 were offered allogeneic stem cell transplant.

Preceding treatment

Chemotherapy

Glucocorticoid therapy

Supportive therapy

CNS therapy, prophylaxis

28-day course

Subsequent treatment

  • See paper for details beyond induction

References

  1. GRAALL-LYSA LL03: Lepretre S, Touzart A, Vermeulin T, Picquenot JM, Tanguy-Schmidt A, Salles G, Lamy T, Béné MC, Raffoux E, Huguet F, Chevallier P, Bologna S, Bouabdallah R, Benichou J, Brière J, Moreau A, Tallon-Simon V, Seris S, Graux C, Asnafi V, Ifrah N, Macintyre E, Dombret H. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study. J Clin Oncol. 2016 Feb 20;34(6):572-80. Epub 2015 Dec 7. link to original article link to data supplement contains dosing details in abstract PubMed NCT00195871

Daunorubicin, Pegaspargase, Vincristine, Dexamethasone

Regimen, modified ABFM

Study Evidence
Vora et al. 2013 (UKALL 2003) Non-randomized portion of RCT

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

  • Cytarabine (Ara-C) by the following age-based criteria:
    • Ages 1 to 1.99: 30 mg IT once on day 1
    • Ages 2 to 2.99: 50 mg IT once on day 1
    • Age 3 and older: 70 mg IT once on day 1
  • Methotrexate (MTX) by the following age-based criteria:
    • Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29
    • Ages 2 to 2.99: 10 mg IT once per day on days 8 & 29
    • Ages 3 to 8.99: 12 mg IT once per day on days 8 & 29
    • Age 9 and older: 15 mg IT once per day on days 8 & 29

4-week course

Subsequent treatment

References

  1. UKALL 2003: Vora A, Goulden N, Wade R, Mitchell C, Hancock J, Hough R, Rowntree C, Richards S. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013 Mar;14(3):199-209. link to original article PubMed ISRCTN07355119

Consolidation after upfront therapy

Etoposide & TBI, then allo HSCT

Regimen

Study Evidence
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) Non-randomized portion of RCT

Chemotherapy

Radiotherapy

Immunotherapy

One course

Immunotherapy

Stem cells transfused on day 0

References

  1. MRC UKALL XII/ECOG E2993: Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. link to original article contains dosing details in manuscript PubMed NCT00002514
    1. Update: Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. link to original article PubMed
    2. Update: Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. link to original article link to PMC article PubMed
    3. Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article contains dosing details in manuscript link to PMC article PubMed

Relapsed or refractory

Nelarabine monotherapy

Regimen variant #1, 5-day dosing

Study Years of enrollment Evidence Efficacy
Berg et al. 2005 1997-2002 Phase 2 (RT) ORR: 14-55%
Zwaan et al. 2017 (GSK 111081) 2009-2014 Phase 4 ORR: 39%

Chemotherapy

21-day cycles


Regimen variant #2, intermittent dosing

Study Years of enrollment Evidence Efficacy
DeAngelo et al. 2007 (CALGB 19801) 1998-2001 Phase 2 (RT) ORR: 41% (95% CI, 15-43)

See paper for details about the schedule.

Chemotherapy

21-day cycle for 3 to 4 cycles (or delayed for count recovery)

References

  1. Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, Billett A, Kurtzberg J, Reaman G, Gaynon P, Whitlock J, Krailo M, Harris MB; Children's Oncology Group. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol. 2005 May 20;23(15):3376-82. link to original article contains dosing details in abstract PubMed
  2. CALGB 19801: DeAngelo DJ, Yu D, Johnson JL, Coutre SE, Stone RM, Stopeck AT, Gockerman JP, Mitchell BS, Appelbaum FR, Larson RA. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007 Jun 15;109(12):5136-42. Epub 2007 Mar 7. link to original article contains dosing details in manuscript link to PMC article PubMed
  3. GSK 111081: Zwaan CM, Kowalczyk J, Schmitt C, Bielorai B, Russo MW, Woessner M, Ranganathan S, Leverger G. Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study. Br J Haematol. 2017 Oct;179(2):284-293. Epub 2017 Aug 2. link to original article contains dosing details in manuscript PubMed NCT00866671
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