Difference between revisions of "Breast cancer, BRCA-mutated"

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*'''2011:''' [http://annonc.oxfordjournals.org/content/22/suppl_6/vi31.full.pdf+html BRCA in breast cancer: ESMO Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/21908500 PubMed]
 
*'''2011:''' [http://annonc.oxfordjournals.org/content/22/suppl_6/vi31.full.pdf+html BRCA in breast cancer: ESMO Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/21908500 PubMed]
  
−
=Advanced or metastatic disease, all lines of therapy=
+
=Advanced or metastatic disease, subsequent lines of therapy=
 
==Capecitabine monotherapy {{#subobject:842c42|Regimen=1}}==
 
==Capecitabine monotherapy {{#subobject:842c42|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
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|-
 
|-
 
|}
 
|}
−
''Patients in OlympiAD had confirmed deleterious or suspected deleterious germline BRCA mutation.''
+
====Biomarker eligibility criteria====
 +
*Confirmed deleterious or suspected deleterious germline BRCA mutation
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
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# '''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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28578601 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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28578601 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]
 
## '''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]
 +
 +
==Carboplatin monotherapy {{#subobject:16h4a8|Regimen=1}}==
 +
{| class="wikitable" style="float:right; margin-left: 5px;"
 +
|-
 +
|[[#top|back to top]]
 +
|}
 +
===Regimen {{#subobject:ujsx06|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/PMC6372067/ Tutt et al. 2018 (TNT)]
 +
|2008-2014
 +
|style="background-color:#1a9851"|Phase III (E-switch-ic)
 +
|[[#Docetaxel_monotherapy|Docetaxel]]
 +
| style="background-color:#1a9850" |Superior ORR (*)
 +
|-
 +
|}
 +
''Note: the rerported efficacy is based on subgroup analysis.''
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
 +
'''21-day cycle for 6 to 8 cycles'''
 +
 +
===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 verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/29713086 PubMed]
 +
 +
==Carboplatin & Paclitaxel {{#subobject:842252|Regimen=1}}==
 +
{| class="wikitable" style="float:right; margin-left: 5px;"
 +
|-
 +
|[[#top|back to top]]
 +
|}
 +
===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 III (C)
 +
|CP & Veliparib
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
====Biomarker eligibility criteria====
 +
*Confirmed deleterious germline BRCA1 or BRCA2 mutation
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
 +
'''21-day cycles'''
 +
 +
===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 verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/32861273 PubMed] NCT02163694
 +
 +
==Docetaxel monotherapy {{#subobject:3e34a8|Regimen=1}}==
 +
{| class="wikitable" style="float:right; margin-left: 5px;"
 +
|-
 +
|[[#top|back to top]]
 +
|}
 +
===Regimen {{#subobject:71bf06|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/PMC6372067/ Tutt et al. 2018 (TNT)]
 +
|2008-2014
 +
|style="background-color:#1a9851"|Phase III (C)
 +
|[[#Carboplatin_monotherapy|Carboplatin]]
 +
| style="background-color:#d73027" |Inferior ORR (*)
 +
|-
 +
|}
 +
''Note: the rerported efficacy is based on subgroup analysis.''
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
 +
'''21-day cycle for 6 to 8 cycles'''
 +
 +
===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 verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/29713086 PubMed]
  
 
==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}==
 
==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}==
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|-
 
|-
 
|}
 
|}
−
''Patients in OlympiAD had confirmed deleterious or suspected deleterious germline BRCA mutation.''
+
====Biomarker eligibility criteria====
 +
*Confirmed deleterious or suspected deleterious germline BRCA mutation
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV over 2 to 5 minutes once per day on days 1 & 8
 
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV over 2 to 5 minutes once per day on days 1 & 8
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# '''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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28578601 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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28578601 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]
 
## '''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]
 +
# '''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://www.nejm.org/doi/full/10.1056/NEJMoa1802905 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed]
  
 
==Olaparib monotherapy {{#subobject:a019cd|Regimen=1}}==
 
==Olaparib monotherapy {{#subobject:a019cd|Regimen=1}}==
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|}
 
|}
 
===Regimen variant #1, 100 mg twice per day {{#subobject:31ed8c|Variant=1}}===
 
===Regimen variant #1, 100 mg twice per day {{#subobject:31ed8c|Variant=1}}===
−
{| class="wikitable" style="width: 50%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 75%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60892-6/fulltext Tutt et al. 2010]
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60892-6/fulltext Tutt et al. 2010 (KU36-44)]
 +
|2007-2008
 
|style="background-color:#91cf61"|Phase II
 
|style="background-color:#91cf61"|Phase II
 
|-
 
|-
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===Regimen variant #3, 400 mg twice per day {{#subobject:31cf8c|Variant=1}}===
 
===Regimen variant #3, 400 mg twice per day {{#subobject:31cf8c|Variant=1}}===
−
{| class="wikitable" style="width: 50%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 75%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60892-6/fulltext Tutt et al. 2010]
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60892-6/fulltext Tutt et al. 2010 (KU36-44)]
 +
|2007-2008
 
|style="background-color:#91cf61"|Phase II
 
|style="background-color:#91cf61"|Phase II
 
|-
 
|-
−
|[http://jco.ascopubs.org/content/33/3/244.long Kaufman et al. 2014 (Study 42)]
+
|[http://jco.ascopubs.org/content/33/3/244.long Kaufman et al. 2014 (D0810C00042)]
 +
|2010-NR
 
|style="background-color:#91cf61"|Phase II
 
|style="background-color:#91cf61"|Phase II
 
|-
 
|-
 
|}
 
|}
−
''Patients in Study 42 had germline BRCA1/2 mutations and had progressed after at least three lines of treatment for metastatic disease.''
+
''Patients in D0810C00042 had germline BRCA1/2 mutations and had progressed after at least three lines of treatment for metastatic disease.''
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Olaparib (Lynparza)]] 400 mg PO twice per day
 
*[[Olaparib (Lynparza)]] 400 mg PO twice per day
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===References===
 
===References===
−
# 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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60892-6/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/20609467 PubMed]
+
# '''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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60892-6/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/20609467 PubMed] NCT00494234
 
<!-- Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. -->
 
<!-- Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. -->
−
# '''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. [http://jco.ascopubs.org/content/33/3/244.long link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25366685 PubMed]
+
# '''D0810C00042:''' 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. [http://jco.ascopubs.org/content/33/3/244.long link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25366685 PubMed] NCT01078662
 
# '''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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28578601 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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28578601 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]
 
## '''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]
Line 156: Line 253:
 
|2013-2017
 
|2013-2017
 
| style="background-color:#1a9851" |Phase III (E-RT-switch-ooc)
 
| style="background-color:#1a9851" |Phase III (E-RT-switch-ooc)
−
|Physician's choice of:<br> 1. [[#Capecitabine_monotherapy|Capecitabine]]<br> 2. Eribulin<br> 3. Gemcitabine<br> 4. Vinorelbine
+
|Physician's choice of:<br> 1. [[#Capecitabine_monotherapy|Capecitabine]]<br> 2. [[#Eribulin_monotherapy|Eribulin]]<br> 3. Gemcitabine<br> 4. [[#Vinorelbine_monotherapy|Vinorelbine]]
 
| style="background-color:#1a9850" |Superior PFS
 
| style="background-color:#1a9850" |Superior PFS
 
|-
 
|-
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# '''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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28578601 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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28578601 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]
 
## '''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]
 +
# '''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://www.nejm.org/doi/full/10.1056/NEJMoa1802905 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed]
  
 
=Additional resources=
 
=Additional resources=

Revision as of 17:52, 11 October 2020

Section editor transclusions

10 regimens on this page
13 variants on this page

Note: this page has regimens which are specific to breast cancer that is BRCA-mutated. Please see the main breast cancer page for other chemotherapy regimens.


Guidelines

ESMO

Advanced or metastatic disease, subsequent lines of therapy

Capecitabine monotherapy

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Robson et al. 2017 (OlympiAD) 2014-2015 Phase III (C) Olaparib Inferior PFS

Biomarker eligibility criteria

  • Confirmed deleterious or suspected deleterious germline BRCA mutation

Chemotherapy

21-day cycles

References

  1. 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. link to original article contains verified protocol PubMed
    1. 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. link to original article link to PMC article PubMed

Carboplatin monotherapy

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Tutt et al. 2018 (TNT) 2008-2014 Phase III (E-switch-ic) Docetaxel Superior ORR (*)

Note: the rerported efficacy is based on subgroup analysis.

Chemotherapy

21-day cycle for 6 to 8 cycles

References

  1. 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. link to original article link to PMC article contains verified protocol PubMed

Carboplatin & Paclitaxel

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Diéras et al. 2020 (BROCADE3) 2014-2018 Phase III (C) CP & Veliparib Inferior PFS

Biomarker eligibility criteria

  • Confirmed deleterious germline BRCA1 or BRCA2 mutation

Chemotherapy

21-day cycles

References

  1. 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. link to original article contains verified protocol PubMed NCT02163694

Docetaxel monotherapy

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Tutt et al. 2018 (TNT) 2008-2014 Phase III (C) Carboplatin Inferior ORR (*)

Note: the rerported efficacy is based on subgroup analysis.

Chemotherapy

21-day cycle for 6 to 8 cycles

References

  1. 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. link to original article link to PMC article contains verified protocol PubMed

Eribulin monotherapy

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Robson et al. 2017 (OlympiAD) 2014-2015 Phase III (C) Olaparib Inferior PFS

Biomarker eligibility criteria

  • Confirmed deleterious or suspected deleterious germline BRCA mutation

Targeted therapy

21-day cycles

References

  1. 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. link to original article contains verified protocol PubMed
    1. 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. link to original article link to PMC article PubMed
  2. 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. link to original article contains protocol PubMed

Olaparib monotherapy

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Regimen variant #1, 100 mg twice per day

Study Years of enrollment Evidence
Tutt et al. 2010 (KU36-44) 2007-2008 Phase II

Targeted therapy

Continued indefinitely

Regimen variant #2, 300 mg twice per day

Study Years of enrollment Evidence Comparator Comparative Efficacy
Robson et al. 2017 (OlympiAD) 2014-2015 Phase III (E-RT-switch-ooc) 1. Capecitabine
2. Eribulin
3. Vinorelbine 		Superior PFS

Patients had confirmed deleterious or suspected deleterious germline BRCA mutation. This is the FDA-approved dose.

Targeted therapy

Continued indefinitely

Regimen variant #3, 400 mg twice per day

Study Years of enrollment Evidence
Tutt et al. 2010 (KU36-44) 2007-2008 Phase II
Kaufman et al. 2014 (D0810C00042) 2010-NR Phase II

Patients in D0810C00042 had germline BRCA1/2 mutations and had progressed after at least three lines of treatment for metastatic disease.

Targeted therapy

Continued indefinitely

References

  1. 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. link to original article PubMed NCT00494234
  2. D0810C00042: 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. link to original article contains verified protocol PubMed NCT01078662
  3. 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. link to original article contains verified protocol PubMed
    1. 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. link to original article link to PMC article PubMed

Talazoparib monotherapy

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Regimen

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
Litton et al. 2018 (EMBRACA) 2013-2017 Phase III (E-RT-switch-ooc) Physician's choice of:
1. Capecitabine
2. Eribulin
3. Gemcitabine
4. Vinorelbine 		Superior PFS

Targeted therapy

Continued indefinitely

References

  1. 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. link to original article contains protocol PubMed

Vinorelbine monotherapy

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Robson et al. 2017 (OlympiAD) 2014-2015 Phase III (C) Olaparib Inferior PFS

Patients had confirmed deleterious or suspected deleterious germline BRCA mutation.

Chemotherapy

21-day cycles

References

  1. 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. link to original article contains verified protocol PubMed
    1. 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. link to original article link to PMC article PubMed
  2. 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. link to original article contains protocol PubMed

Additional resources

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