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

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=Advanced or metastatic disease, all lines of therapy=
 
=Advanced or metastatic disease, all lines of therapy=
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==Capecitabine monotherapy {{#subobject:842c42|Regimen=1}}==
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{| class="wikitable" style="float:right; margin-left: 5px;"
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|-
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|[[#top|back to top]]
 +
|}
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===Regimen {{#subobject:fb2810|Variant=1}}===
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{| class="wikitable" 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%"|Years of study
 +
|-
 +
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
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| style="background-color:#1a9851" |Phase III (C)
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|[[#Olaparib_monotherapy|Olaparib]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|2014-2015
 +
|-
 +
|}
 +
''Patients in OlympiAD had confirmed deleterious or suspected deleterious germline BRCA mutation.''
 +
====Chemotherapy====
 +
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 +
 +
'''21-day cycles'''
 +
===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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://academic.oup.com/annonc/article/30/4/558/5299440 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503629/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30689707 PubMed]
 +
 +
==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}==
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{| class="wikitable" style="float:right; margin-left: 5px;"
 +
|-
 +
|[[#top|back to top]]
 +
|}
 +
===Regimen {{#subobject:25ef0|Variant=1}}===
 +
{| class="wikitable" 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%"|Years of study
 +
|-
 +
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[#Olaparib_monotherapy|Olaparib]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|2014-2015
 +
|-
 +
|}
 +
''Patients in OlympiAD had confirmed deleterious or suspected deleterious germline BRCA mutation.''
 +
====Chemotherapy====
 +
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV over 2 to 5 minutes once per day on days 1 & 8
 +
 +
'''21-day cycles'''
 +
 +
===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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://academic.oup.com/annonc/article/30/4/558/5299440 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503629/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30689707 PubMed]
 +
 
==Olaparib monotherapy {{#subobject:a019cd|Regimen=1}}==
 
==Olaparib monotherapy {{#subobject:a019cd|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
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===Variant #2, 300 mg twice per day {{#subobject:3b0774|Variant=1}}===
 
===Variant #2, 300 mg twice per day {{#subobject:3b0774|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 25%"|Comparator
+
!style="width: 20%"|Comparator
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 20%"|Years of study
 
|-
 
|-
 
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
−
|style="background-color:#1a9851"|Phase III (E-switch-ooc)
+
|style="background-color:#1a9851"|Phase III (E-RT-switch-ooc)
−
|1. [[Breast_cancer#Capecitabine_monotherapy_3|Capecitabine]]<br> 2. [[Breast_cancer#Eribulin_monotherapy|Eribulin]]<br> 3. [[Breast_cancer#Vinorelbine_monotherapy_2|Vinorelbine]]
+
|1. [[#Capecitabine_monotherapy|Capecitabine]]<br> 2. [[#Eribulin_monotherapy|Eribulin]]<br> 3. [[#Vinorelbine_monotherapy|Vinorelbine]]
 
|style="background-color:#1a9850"|Superior PFS
 
|style="background-color:#1a9850"|Superior PFS
 +
|2014-2015
 
|-
 
|-
 
|}
 
|}
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|}
 
|}
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 25%"|Comparator
+
!style="width: 20%"|Comparator
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 20%"|Years of study
 
|-
 
|-
 
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1802905 Litton et al. 2018 (EMBRACA)]
 
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1802905 Litton et al. 2018 (EMBRACA)]
 
| 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<br> 2. Eribulin<br> 3. Gemcitabine<br> 4. Vinorelbine
+
|Physician's choice of:<br> 1. [[#Capecitabine_monotherapy|Capecitabine]]<br> 2. Eribulin<br> 3. Gemcitabine<br> 4. Vinorelbine
 
| style="background-color:#1a9850" |Superior PFS
 
| style="background-color:#1a9850" |Superior PFS
 +
|2013-2017
 
|-
 
|-
 
|}
 
|}
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===References===
 
===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://www.nejm.org/doi/full/10.1056/NEJMoa1802905 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30110579 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://www.ncbi.nlm.nih.gov/pubmed/30110579 PubMed]
 +
 +
==Vinorelbine monotherapy {{#subobject:5c104c|Regimen=1}}==
 +
{| class="wikitable" style="float:right; margin-left: 5px;"
 +
|-
 +
|[[#top|back to top]]
 +
|}
 +
===Regimen {{#subobject:7321fd|Variant=1}}===
 +
{| class="wikitable" 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%"|Years of study
 +
|-
 +
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[#Olaparib_monotherapy|Olaparib]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|2014-2015
 +
|-
 +
|}
 +
''Patients had confirmed deleterious or suspected deleterious germline BRCA mutation.''
 +
====Chemotherapy====
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
 +
'''21-day cycles'''
 +
===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://www.nejm.org/doi/full/10.1056/NEJMoa1706450 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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://academic.oup.com/annonc/article/30/4/558/5299440 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503629/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30689707 PubMed]
  
 
=Additional resources=
 
=Additional resources=

Revision as of 03:28, 24 December 2019

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, all lines of therapy

Capecitabine monotherapy

back to top

Regimen

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

Patients in OlympiAD 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

Eribulin monotherapy

back to top

Regimen

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

Patients in OlympiAD 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

Olaparib monotherapy

back to top

Variant #1, 100 mg twice per day

Study Evidence
Tutt et al. 2010 Phase II

Chemotherapy

Continued indefinitely

Variant #2, 300 mg twice per day

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

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

Chemotherapy

Continued indefinitely

Variant #3, 400 mg twice per day

Study Evidence
Tutt et al. 2010 Phase II
Kaufman et al. 2014 (Study 42) Phase II

Patients in Study 42 had germline BRCA1/2 mutations and had progressed after at least three lines of treatment for metastatic disease.

Chemotherapy

Continued indefinitely

References

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

back to top

Regimen

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

Chemotherapy

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

back to top

Regimen

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

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

Additional resources

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