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

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m (Text replacement - "(NCT[0-9]{8})" to "[https://clinicaltrials.gov/ct2/show/$1 Clinical Trial Registry]")
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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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{{#lst:Editorial board transclusions|breast}}
 
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{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Guidelines=
 
=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 
==[http://www.asc.org/ ASCO]==
 
==[http://www.asc.org/ ASCO]==
−
*'''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]
+
*'''2024:''' Bedrosian et al. [https://doi.org/10.1200/jco.23.02225 Germline Testing in Patients With Breast Cancer: ASCO–Society of Surgical Oncology Guideline] [https://pubmed.ncbi.nlm.nih.gov/38175972/ PubMed]
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==[http://www.esmo.org/ ESMO]==
+
*'''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] [https://pubmed.ncbi.nlm.nih.gov/34343058/ PubMed]
−
*'''2011:''' Balmaña et al. [https://doi.org/10.1093/annonc/mdr373 BRCA in breast cancer: ESMO Clinical Practice Guidelines]
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*'''2020:''' Tung et al. [https://doi.org/10.1200/jco.20.00299 Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline] [https://pubmed.ncbi.nlm.nih.gov/32243226/ PubMed]
 +
 
 +
==[https://www.esmo.org/ ESMO]==
 +
*'''2011:''' Balmaña et al. [https://doi.org/10.1093/annonc/mdr373 BRCA in breast cancer: ESMO Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/21908500/ PubMed]
 +
==NCCN==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419 NCCN Guidelines - Breast Cancer].''
 +
 
 
=Adjuvant therapy=
 
=Adjuvant therapy=
 
==Olaparib monotherapy {{#subobject:56hxcd|Regimen=1}}==
 
==Olaparib monotherapy {{#subobject:56hxcd|Regimen=1}}==
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|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9126186/ Tutt et al. 2021 (OlympiA)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9126186/ Tutt et al. 2021 (OlympiA)]
−
{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
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<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-331-1 <span style="color:white;">ESMO-MCBS (A)</span>]'''
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-331-1 <span style="color:white;">ESMO-MCBS (A)</span>]'''
 
|-
 
|-
−
|}
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|} -->
 
|2014-2019
 
|2014-2019
 
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup> (secondary endpoint)<br>OS48: 89.8% vs 86.4%<br>(HR 0.68, 98.5% CI 0.47-0.97)
+
| style="background-color:#1a9850" |Superior iDFS (primary endpoint)<br>iDFS36: 85.9% vs 77.1%<br>(HR 0.58, 99.5% CI 0.41-0.82)<br><br>Superior OS<sup>1</sup> (secondary endpoint)<br>OS48: 89.8% vs 86.4%<br>(HR 0.68, 98.5% CI 0.47-0.97)
 
|-
 
|-
 
|}
 
|}
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</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://www.ncbi.nlm.nih.gov/pmc/articles/pmc9126186/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34081848/ PubMed] [https://clinicaltrials.gov/ct2/show/NCT02032823 Clinical Trial Registry]
+
# '''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://www.ncbi.nlm.nih.gov/pmc/articles/pmc9126186/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34081848/ PubMed] [https://clinicaltrials.gov/study/NCT02032823 NCT02032823]
 
##'''Update:''' Geyer CE Jr, Garber JE, Gelber RD, Yothers G, Taboada M, Ross L, Rastogi P, Cui K, Arahmani A, Aktan G, Armstrong AC, Arnedos M, Balmaña J, Bergh J, Bliss J, Delaloge S, Domchek SM, Eisen A, Elsafy F, Fein LE, Fielding A, Ford JM, Friedman S, Gelmon KA, Gianni L, Gnant M, Hollingsworth SJ, Im SA, Jager A, Jóhannsson ÓÞ, Lakhani SR, Janni W, Linderholm B, Liu TW, Loman N, Korde L, Loibl S, Lucas PC, Marmé F, Martinez de Dueñas E, McConnell R, Phillips KA, Piccart M, Rossi G, Schmutzler R, Senkus E, Shao Z, Sharma P, Singer CF, Španić T, Stickeler E, Toi M, Traina TA, Viale G, Zoppoli G, Park YH, Yerushalmi R, Yang H, Pang D, Jung KH, Mailliez A, Fan Z, Tennevet I, Zhang J, Nagy T, Sonke GS, Sun Q, Parton M, Colleoni MA, Schmidt M, Brufsky AM, Razaq W, Kaufman B, Cameron D, Campbell C, Tutt ANJ; OlympiA Clinical Trial Steering Committee and Investigators. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022 Dec 1;33(12):1250-1268. Epub 2022 Oct 10. [https://doi.org/10.1016/j.annonc.2022.09.159 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36228963/ PubMed]
 
##'''Update:''' Geyer CE Jr, Garber JE, Gelber RD, Yothers G, Taboada M, Ross L, Rastogi P, Cui K, Arahmani A, Aktan G, Armstrong AC, Arnedos M, Balmaña J, Bergh J, Bliss J, Delaloge S, Domchek SM, Eisen A, Elsafy F, Fein LE, Fielding A, Ford JM, Friedman S, Gelmon KA, Gianni L, Gnant M, Hollingsworth SJ, Im SA, Jager A, Jóhannsson ÓÞ, Lakhani SR, Janni W, Linderholm B, Liu TW, Loman N, Korde L, Loibl S, Lucas PC, Marmé F, Martinez de Dueñas E, McConnell R, Phillips KA, Piccart M, Rossi G, Schmutzler R, Senkus E, Shao Z, Sharma P, Singer CF, Španić T, Stickeler E, Toi M, Traina TA, Viale G, Zoppoli G, Park YH, Yerushalmi R, Yang H, Pang D, Jung KH, Mailliez A, Fan Z, Tennevet I, Zhang J, Nagy T, Sonke GS, Sun Q, Parton M, Colleoni MA, Schmidt M, Brufsky AM, Razaq W, Kaufman B, Cameron D, Campbell C, Tutt ANJ; OlympiA Clinical Trial Steering Committee and Investigators. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022 Dec 1;33(12):1250-1268. Epub 2022 Oct 10. [https://doi.org/10.1016/j.annonc.2022.09.159 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36228963/ PubMed]
 +
##'''PRO analysis:''' Ganz PA, Bandos H, Španić T, Friedman S, Müller V, Kuemmel S, Delaloge S, Brain E, Toi M, Yamauchi H, de Dueñas EM, Armstrong A, Im SA, Song CG, Zheng H, Sarosiek T, Sharma P, Geng C, Fu P, Rhiem K, Frauchiger-Heuer H, Wimberger P, t'Kint de Roodenbeke D, Liao N, Goodwin A, Chakiba-Brugère C, Friedlander M, Lee KS, Giacchetti S, Takano T, Henao-Carrasco F, Virani S, Valdes-Albini F, Domchek SM, Bane C, McCarron EC, Mita M, Rossi G, Rastogi P, Fielding A, Gelber RD, Scheepers ED, Cameron D, Garber J, Geyer CE, Tutt ANJ. Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in gBRCA1/2 Mutations and High-Risk Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer. J Clin Oncol. 2024 Apr 10;42(11):1288-1300. Epub 2024 Feb 1. [https://doi.org/10.1200/jco.23.01214 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38301187/ PubMed]
  
 
=Advanced or metastatic disease, subsequent lines of therapy=
 
=Advanced or metastatic disease, subsequent lines of therapy=
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</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] [https://clinicaltrials.gov/ct2/show/NCT02000622 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT02000622 NCT02000622]
 
## '''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://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579/ PubMed] [https://clinicaltrials.gov/ct2/show/NCT01945775 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT01945775 NCT01945775]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
## '''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]
 
## '''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]
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|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
|[[#Docetaxel_monotherapy|Docetaxel]]
 
|[[#Docetaxel_monotherapy|Docetaxel]]
−
| style="background-color:#1a9850" |Superior ORR<sup>1</sup>
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| style="background-color:#1a9850" |Superior ORR<sup>1</sup> (primary endpoint)
 
|-
 
|-
 
|}
 
|}
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</div></div>
 
</div></div>
 
===References===
 
===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://doi.org/10.1038/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] [https://clinicaltrials.gov/ct2/show/NCT00532727 Clinical Trial Registry]
+
# '''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://doi.org/10.1038/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] [https://clinicaltrials.gov/study/NCT00532727 NCT00532727]
 
==Carboplatin & Paclitaxel (CP) {{#subobject:842252|Regimen=1}}==
 
==Carboplatin & Paclitaxel (CP) {{#subobject:842252|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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|2014-2018
 
|2014-2018
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Veliparib_88|CP & Veliparib]]
+
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Veliparib_777|CP & Veliparib]]
−
| style="background-color:#d73027" |Inferior PFS
+
| style="background-color:#d73027" |Inferior PFS (primary endpoint)<br><br>Did not meet secondary endpoint of OS<sup>1</sup>
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2024 update.''
 
<div class="toccolours" style="background-color:#fdcdac">
 
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
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</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] [https://clinicaltrials.gov/ct2/show/NCT02163694 Clinical Trial Registry]
+
#'''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] [https://clinicaltrials.gov/study/NCT02163694 NCT02163694]
 +
##'''Update:''' Diéras V, Han HS, Wildiers H, Friedlander M, Ayoub JP, Puhalla SL, Loirat D, Ratajczak C, Adamu H, Girardi V, Arun BK. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): Final overall survival results from a randomized phase 3 trial. Eur J Cancer. 2024 Mar;200:113580. Epub 2024 Jan 28. [https://doi.org/10.1016/j.ejca.2024.113580 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38309017/ PubMed]
 +
 
 
==Docetaxel monotherapy {{#subobject:3e34a8|Regimen=1}}==
 
==Docetaxel monotherapy {{#subobject:3e34a8|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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</div></div>
 
</div></div>
 
===References===
 
===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://doi.org/10.1038/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] [https://clinicaltrials.gov/ct2/show/NCT00532727 Clinical Trial Registry]
+
# '''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://doi.org/10.1038/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] [https://clinicaltrials.gov/study/NCT00532727 NCT00532727]
 
==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}==
 
==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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</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] [https://clinicaltrials.gov/ct2/show/NCT02000622 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT02000622 NCT02000622]
 
## '''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://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579/ PubMed] [https://clinicaltrials.gov/ct2/show/NCT01945775 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT01945775 NCT01945775]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
## '''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]
 
## '''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]
Line 241: Line 252:
 
</div></div>
 
</div></div>
 
===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://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579/ PubMed] [https://clinicaltrials.gov/ct2/show/NCT01945775 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT01945775 NCT01945775]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
## '''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]
 
## '''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]
Line 276: Line 287:
 
|-
 
|-
 
|[https://doi.org/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
 
|[https://doi.org/10.1056/NEJMoa1706450 Robson et al. 2017 (OlympiAD)]
−
{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-166-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-166-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 
|-
 
|-
−
|}
+
|} -->
 
|2014-04-07 to 2015-11-27
 
|2014-04-07 to 2015-11-27
 
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
 
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
−
|1a. [[#Capecitabine_monotherapy|Capecitabine]]<br>1b. [[#Eribulin_monotherapy|Eribulin]]<br>1c. [[#Vinorelbine_monotherapy|Vinorelbine]]
+
|Investigator's choice of:<br>1a. [[#Capecitabine_monotherapy|Capecitabine]]<br>1b. [[#Eribulin_monotherapy|Eribulin]]<br>1c. [[#Vinorelbine_monotherapy|Vinorelbine]]
−
|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 7.0 mo vs 4.2 mo <br>(HR 0.58, 95% CI 0.43-0.80)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 19.3 vs 17.1 mo<br>(HR 0.90, 95% CI 0.66-1.23)
+
|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 7.0 vs 4.2 mo <br>(HR 0.58, 95% CI 0.43-0.80)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 19.3 vs 17.1 mo<br>(HR 0.90, 95% CI 0.66-1.23)
 
|-
 
|-
 
|}
 
|}
Line 297: Line 308:
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
 +
 
===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 sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
Line 308: Line 320:
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ Kaufman et al. 2014 (Study 42)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ Kaufman et al. 2014 (Study 42)]
−
|2010-2012
+
|2010-02-21 to 2012-07-31
 
|style="background-color:#91cf61"|Phase 2
 
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
Line 324: Line 336:
 
</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] [https://clinicaltrials.gov/ct2/show/NCT00494234 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT00494234 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. [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] [https://clinicaltrials.gov/ct2/show/NCT01078662 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT01078662 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://doi.org/10.1056/NEJMoa1706450 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28578601/ PubMed] [https://clinicaltrials.gov/ct2/show/NCT02000622 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT02000622 NCT02000622]
 
## '''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 351: Line 363:
 
|-
 
|-
 
|[https://doi.org/10.1056/NEJMoa1802905 Litton et al. 2018 (EMBRACA)]
 
|[https://doi.org/10.1056/NEJMoa1802905 Litton et al. 2018 (EMBRACA)]
−
{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-165-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-165-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 
|-
 
|-
−
|}
+
|} -->
 
|2013-10 to 2017-04
 
|2013-10 to 2017-04
 
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
Line 372: Line 384:
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''ABRAZO:''' Turner NC, Telli ML, Rugo HS, Mailliez A, Ettl J, Grischke EM, Mina LA, Balmaña J, Fasching PA, Hurvitz SA, Wardley AM, Chappey C, Hannah AL, Robson ME; ABRAZO Study Group. A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Clin Cancer Res. 2019 May 1;25(9):2717-2724. Epub 2018 Dec 18. [https://doi.org/10.1158/1078-0432.CCR-18-1891 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30563931/ PubMed] [https://clinicaltrials.gov/ct2/show/NCT02034916 Clinical Trial Registry]
+
# '''ABRAZO:''' Turner NC, Telli ML, Rugo HS, Mailliez A, Ettl J, Grischke EM, Mina LA, Balmaña J, Fasching PA, Hurvitz SA, Wardley AM, Chappey C, Hannah AL, Robson ME; ABRAZO Study Group. A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Clin Cancer Res. 2019 May 1;25(9):2717-2724. Epub 2018 Dec 18. [https://doi.org/10.1158/1078-0432.CCR-18-1891 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30563931/ PubMed] [https://clinicaltrials.gov/study/NCT02034916 NCT02034916]
−
# '''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] [https://clinicaltrials.gov/ct2/show/NCT01945775 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT01945775 NCT01945775]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
## '''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]
 
## '''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]
Line 429: Line 441:
 
</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] [https://clinicaltrials.gov/ct2/show/NCT02000622 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT02000622 NCT02000622]
 
## '''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://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579/ PubMed] [https://clinicaltrials.gov/ct2/show/NCT01945775 Clinical Trial Registry]
+
# '''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] [https://clinicaltrials.gov/study/NCT01945775 NCT01945775]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
##'''PRO analysis:''' Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. [https://doi.org/10.1093/annonc/mdy257 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30124753/ PubMed]
 
## '''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]
 
## '''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]

Latest revision as of 17:45, 23 June 2024

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Section editor
TBA
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

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO

ESMO

NCCN

Adjuvant therapy

Olaparib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Tutt et al. 2021 (OlympiA) 2014-2019 Phase 3 (E-RT-esc) Placebo Superior iDFS (primary endpoint)
iDFS36: 85.9% vs 77.1%
(HR 0.58, 99.5% CI 0.41-0.82)

Superior OS1 (secondary endpoint)
OS48: 89.8% vs 86.4%
(HR 0.68, 98.5% CI 0.47-0.97)

1Reported efficacy is based on the 2022 update.

Preceding treatment

Targeted therapy

28-day cycle for 13 cycles (1 year)

References

  1. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02032823
    1. Update: Geyer CE Jr, Garber JE, Gelber RD, Yothers G, Taboada M, Ross L, Rastogi P, Cui K, Arahmani A, Aktan G, Armstrong AC, Arnedos M, Balmaña J, Bergh J, Bliss J, Delaloge S, Domchek SM, Eisen A, Elsafy F, Fein LE, Fielding A, Ford JM, Friedman S, Gelmon KA, Gianni L, Gnant M, Hollingsworth SJ, Im SA, Jager A, Jóhannsson ÓÞ, Lakhani SR, Janni W, Linderholm B, Liu TW, Loman N, Korde L, Loibl S, Lucas PC, Marmé F, Martinez de Dueñas E, McConnell R, Phillips KA, Piccart M, Rossi G, Schmutzler R, Senkus E, Shao Z, Sharma P, Singer CF, Španić T, Stickeler E, Toi M, Traina TA, Viale G, Zoppoli G, Park YH, Yerushalmi R, Yang H, Pang D, Jung KH, Mailliez A, Fan Z, Tennevet I, Zhang J, Nagy T, Sonke GS, Sun Q, Parton M, Colleoni MA, Schmidt M, Brufsky AM, Razaq W, Kaufman B, Cameron D, Campbell C, Tutt ANJ; OlympiA Clinical Trial Steering Committee and Investigators. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022 Dec 1;33(12):1250-1268. Epub 2022 Oct 10. link to original article PubMed
    2. PRO analysis: Ganz PA, Bandos H, Španić T, Friedman S, Müller V, Kuemmel S, Delaloge S, Brain E, Toi M, Yamauchi H, de Dueñas EM, Armstrong A, Im SA, Song CG, Zheng H, Sarosiek T, Sharma P, Geng C, Fu P, Rhiem K, Frauchiger-Heuer H, Wimberger P, t'Kint de Roodenbeke D, Liao N, Goodwin A, Chakiba-Brugère C, Friedlander M, Lee KS, Giacchetti S, Takano T, Henao-Carrasco F, Virani S, Valdes-Albini F, Domchek SM, Bane C, McCarron EC, Mita M, Rossi G, Rastogi P, Fielding A, Gelber RD, Scheepers ED, Cameron D, Garber J, Geyer CE, Tutt ANJ. Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in gBRCA1/2 Mutations and High-Risk Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer. J Clin Oncol. 2024 Apr 10;42(11):1288-1300. Epub 2024 Feb 1. link to original article PubMed

Advanced or metastatic disease, subsequent lines of therapy

Capecitabine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Litton et al. 2018 (EMBRACA) 2013-10 to 2017-04 Phase 3 (C) Talazoparib Inferior PFS
Robson et al. 2017 (OlympiAD) 2014-04-07 to 2015-11-27 Phase 3 (C) Olaparib Inferior PFS

Biomarker eligibility criteria

  • EMBRACA: Germline BRCA1 or BRCA2 mutation
  • OlympiAD: 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 dosing details in manuscript PubMed NCT02000622
    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 dosing details in supplement PubMed NCT01945775
    1. PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article PubMed
    2. 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. link to original article PubMed

Carboplatin monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Tutt et al. 2018 (TNT) 2008-2014 Phase 3 (E-switch-ic) Docetaxel Superior ORR1 (primary endpoint)

1Reported 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 dosing details in manuscript PubMed NCT00532727

Carboplatin & Paclitaxel (CP)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Diéras et al. 2020 (BROCADE3) 2014-2018 Phase 3 (C) CP & Veliparib Inferior PFS (primary endpoint)

Did not meet secondary endpoint of OS1

1Reported efficacy is based on the 2024 update.

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 dosing details in manuscript PubMed NCT02163694
    1. Update: Diéras V, Han HS, Wildiers H, Friedlander M, Ayoub JP, Puhalla SL, Loirat D, Ratajczak C, Adamu H, Girardi V, Arun BK. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): Final overall survival results from a randomized phase 3 trial. Eur J Cancer. 2024 Mar;200:113580. Epub 2024 Jan 28. link to original article PubMed

Docetaxel monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Tutt et al. 2018 (TNT) 2008-2014 Phase 3 (C) Carboplatin Inferior ORR1

1Reported 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 dosing details in manuscript PubMed NCT00532727

Eribulin monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Litton et al. 2018 (EMBRACA) 2013-10 to 2017-04 Phase 3 (C) Talazoparib Inferior PFS
Robson et al. 2017 (OlympiAD) 2014-04-07 to 2015-11-27 Phase 3 (C) Olaparib Inferior PFS

Biomarker eligibility criteria

  • EMBRACA: Germline BRCA1 or BRCA2 mutation
  • OlympiAD: 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 dosing details in manuscript PubMed NCT02000622
    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 dosing details in supplement PubMed NCT01945775
    1. PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article PubMed
    2. 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. link to original article PubMed

Gemcitabine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Litton et al. 2018 (EMBRACA) 2013-10 to 2017-04 Phase 3 (C) Talazoparib Inferior PFS

Biomarker eligibility criteria

  • Germline BRCA1 or BRCA2 mutation

Chemotherapy

21-day cycles

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 dosing details in supplement PubMed NCT01945775
    1. PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article PubMed
    2. 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. link to original article PubMed

Olaparib monotherapy

Regimen variant #1, 100 mg twice per day

Study Dates of enrollment Evidence
Tutt et al. 2010 (KU36-44) 2007-2008 Phase 2

Targeted therapy

Continued indefinitely


Regimen variant #2, 300 mg twice per day

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Robson et al. 2017 (OlympiAD) 2014-04-07 to 2015-11-27 Phase 3 (E-RT-switch-ooc) Investigator's choice of:
1a. Capecitabine
1b. Eribulin
1c. Vinorelbine 		Superior PFS (primary endpoint)
Median PFS: 7.0 vs 4.2 mo
(HR 0.58, 95% CI 0.43-0.80)

Did not meet secondary endpoint of OS1
Median OS: 19.3 vs 17.1 mo
(HR 0.90, 95% CI 0.66-1.23)

1Reported efficacy for OS is based on the 2019 update.

Biomarker eligibility criteria

  • Confirmed deleterious or suspected deleterious germline BRCA mutation

Targeted therapy

Continued indefinitely


Regimen variant #3, 400 mg twice per day

Study Dates of enrollment Evidence
Tutt et al. 2010 (KU36-44) 2007-2008 Phase 2
Kaufman et al. 2014 (Study 42) 2010-02-21 to 2012-07-31 Phase 2

Biomarker eligibility criteria

  • Study 42: Germline BRCA1/2 mutations

Prior treatment criteria

  • Study 42: Progression 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. 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 dosing details in manuscript link to PMC article 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 dosing details in manuscript PubMed NCT02000622
    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

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Turner et al. 2018 (ABRAZO) 2014-05 to 2016-02 Phase 2
Litton et al. 2018 (EMBRACA) 2013-10 to 2017-04 Phase 3 (E-RT-switch-ooc) Physician's choice of:
1a. Capecitabine
1b. Eribulin
1c. Gemcitabine
1d. Vinorelbine 		Superior PFS (primary endpoint)
Median PFS: 8.6 vs 5.6 mo
(HR 0.54, 95% CI 0.41-0.71)

Did not meet secondary endpoint of OS1
Median OS: 19.3 vs 19.5 mo
(HR 0.85, 95% CI 0.67-1.07)

1Reported efficacy for OS is based on the 2020 update.

Biomarker eligibility criteria

  • Germline BRCA1 or BRCA2 mutation

Targeted therapy

Continued indefinitely

References

  1. ABRAZO: Turner NC, Telli ML, Rugo HS, Mailliez A, Ettl J, Grischke EM, Mina LA, Balmaña J, Fasching PA, Hurvitz SA, Wardley AM, Chappey C, Hannah AL, Robson ME; ABRAZO Study Group. A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Clin Cancer Res. 2019 May 1;25(9):2717-2724. Epub 2018 Dec 18. link to original article contains dosing details in abstract PubMed NCT02034916
  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 dosing details in abstract PubMed NCT01945775
    1. PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article PubMed
    2. 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. link to original article PubMed

Vinorelbine monotherapy

Regimen variant #1, 2 out of 3 weeks

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Robson et al. 2017 (OlympiAD) 2014-04-07 to 2015-11-27 Phase 3 (C) Olaparib Inferior PFS

Biomarker eligibility criteria

  • Confirmed deleterious or suspected deleterious germline BRCA mutation

Chemotherapy

21-day cycles


Regimen variant #2, weekly

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Litton et al. 2018 (EMBRACA) 2013-10 to 2017-04 Phase 3 (C) Talazoparib Inferior PFS

Biomarker eligibility criteria

  • Germline BRCA1 or BRCA2 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 dosing details in manuscript PubMed NCT02000622
    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 dosing details in supplement PubMed NCT01945775
    1. PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article PubMed
    2. 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. link to original article PubMed

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