Revision as of 12:31, 22 October 2022

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

ASCO

2021: Tung et al. 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

ESMO

2011: Balmaña et al. BRCA in breast cancer: ESMO Clinical Practice Guidelines

Adjuvant therapy

Olaparib monotherapy

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Tutt et al. 2021 (OlympiA)	2014-2019	Phase 3 (E-RT-esc)	Placebo	Superior invasive DFS IDFS36: 86% vs 77% (HR 0.58, 99.5% CI 0.41-0.82)

Preceding treatment

Primary local treatment +/- (neo-)adjuvant therapy

Targeted therapy

Olaparib (Lynparza) 300 mg PO twice per day

28-day cycle for 13 cycles (1 year)

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. link to original article contains dosing details in manuscript PubMed NCT02032823

Advanced or metastatic disease, subsequent lines of therapy

Capecitabine monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Litton et al. 2018 (EMBRACA)	2013-2017	Phase 3 (C)	Talazoparib	Inferior PFS
Robson et al. 2017 (OlympiAD)	2014-2015	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

Capecitabine (Xeloda) 1250 mg/m² 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. 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
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. 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	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Tutt et al. 2018 (TNT)	2008-2014	Phase 3 (E-switch-ic)	Docetaxel	Superior ORR¹

¹Reported efficacy is based on subgroup analysis.

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1

21-day cycle for 6 to 8 cycles

References

TNT: Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. Epub 2018 Apr 30. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00532727

Carboplatin & Paclitaxel (CP)

Regimen

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

Biomarker eligibility criteria

Confirmed deleterious germline BRCA1 or BRCA2 mutation

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

21-day cycles

References

BROCADE3: Diéras V, Han HS, Kaufman B, Wildiers H, Friedlander M, Ayoub JP, Puhalla SL, Bondarenko I, Campone M, Jakobsen EH, Jalving M, Oprean C, Palácová M, Park YH, Shparyk Y, Yañez E, Khandelwal N, Kundu MG, Dudley M, Ratajczak CK, Maag D, Arun BK. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Oct;21(10):1269-1282. Epub 2020 Aug 27. link to original article contains dosing details in manuscript PubMed NCT02163694

Docetaxel monotherapy

Regimen

Study	Years 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

Docetaxel (Taxotere) 100 mg/m² IV once on day 1

21-day cycle for 6 to 8 cycles

References

TNT: Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. Epub 2018 Apr 30. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00532727

Eribulin monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Litton et al. 2018 (EMBRACA)	2013-2017	Phase 3 (C)	Talazoparib	Inferior PFS
Robson et al. 2017 (OlympiAD)	2014-2015	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

Eribulin (Halaven) 1.4 mg/m² 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. 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
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. 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	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Litton et al. 2018 (EMBRACA)	2013-2017	Phase 3 (C)	Talazoparib	Inferior PFS

Biomarker eligibility criteria

Germline BRCA1 or BRCA2 mutation

Chemotherapy

Gemcitabine (Gemzar) 1250 mg/m² IV over 30 minutes once per day on days 1 & 8

21-day cycles

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. link to original article contains dosing details in supplement PubMed NCT01945775
1. Update: Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. link to original article PubMed

Olaparib monotherapy

Regimen variant #1, 100 mg twice per day

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

Targeted therapy

Olaparib (Lynparza) 100 mg PO twice per day

Continued indefinitely

Regimen variant #2, 300 mg twice per day

FDA-recommended dose

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Robson et al. 2017 (OlympiAD)	2014-2015	Phase 3 (E-RT-switch-ooc)	1a. Capecitabine 1b. Eribulin 1c. Vinorelbine	Superior PFS Median PFS: 7.0 mo vs 4.2 mo (HR 0.58, 95% CI 0.43-0.80)

Biomarker eligibility criteria

Confirmed deleterious or suspected deleterious germline BRCA mutation

Targeted therapy

Olaparib (Lynparza) 300 mg PO twice per day

Continued indefinitely

Regimen variant #3, 400 mg twice per day

Study	Years of enrollment	Evidence
Tutt et al. 2010 (KU36-44)	2007-2008	Phase 2
Kaufman et al. 2014 (Study 42)	2010-NR	Phase 2

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

Targeted therapy

Olaparib (Lynparza) 400 mg PO twice per day

Continued indefinitely

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. link to original article PubMed NCT00494234
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
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	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Litton et al. 2018 (EMBRACA)	2013-2017	Phase 3 (E-RT-switch-ooc)	Physician's choice of: 1a. Capecitabine 1b. Eribulin 1c. Gemcitabine 1d. Vinorelbine	Superior PFS Median PFS: 8.6 vs 5.6 mo (HR 0.54, 95% CI 0.41-0.71)

Biomarker eligibility criteria

Germline BRCA1 or BRCA2 mutation

Targeted therapy

Talazoparib (Talzenna) 1 mg PO once per day

Continued indefinitely

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. link to original article contains dosing details in abstract PubMed NCT01945775
1. Update: Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. link to original article PubMed

Vinorelbine monotherapy

Regimen variant #1, 2 out of 3 weeks

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Robson et al. 2017 (OlympiAD)	2014-2015	Phase 3 (C)	Olaparib	Inferior PFS

Biomarker eligibility criteria

Confirmed deleterious or suspected deleterious germline BRCA mutation

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV once per day on days 1 & 8

21-day cycles

Regimen variant #2, weekly

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

Biomarker eligibility criteria

Germline BRCA1 or BRCA2 mutation

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV over 6 to 10 minutes once per day on days 1, 8, 15

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. 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
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. 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

Additional resources

@@ Line 14: / Line 14: @@
 ==[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]
 ==[http://www.esmo.org/ ESMO]==
 *'''2011:''' Balmaña et al. [https://doi.org/10.1093/annonc/mdr373 BRCA in breast cancer: ESMO Clinical Practice Guidelines]
 =Adjuvant therapy=
 ==Olaparib monotherapy {{#subobject:56hxcd|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:3b0yga|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 40: / Line 38: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Breast_cancer_surgery|Primary local treatment]] +/- (neo-)adjuvant therapy
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Olaparib (Lynparza)]] 300 mg PO twice per day
 '''28-day cycle for 13 cycles (1 year)'''
+</div></div>
 ===References===
 # '''OlympiA:''' Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, Gelber RD, de Azambuja E, Fielding A, Balmaña J, Domchek SM, Gelmon KA, Hollingsworth SJ, Korde LA, Linderholm B, Bandos H, Senkus E, Suga JM, Shao Z, Pippas AW, Nowecki Z, Huzarski T, Ganz PA, Lucas PC, Baker N, Loibl S, McConnell R, Piccart M, Schmutzler R, Steger GG, Costantino JP, Arahmani A, Wolmark N, McFadden E, Karantza V, Lakhani SR, Yothers G, Campbell C, Geyer CE Jr; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021 Jun 24;384(25):2394-2405. Epub 2021 Jun 3. [https://doi.org/10.1056/nejmoa2105215 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34081848/ PubMed] NCT02032823
 =Advanced or metastatic disease, subsequent lines of therapy=
 ==Capecitabine monotherapy {{#subobject:842c42|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:fb2810|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 75: / Line 73: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *EMBRACA: Germline BRCA1 or BRCA2 mutation
 *OlympiAD: Confirmed deleterious or suspected deleterious germline BRCA mutation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 '''21-day cycles'''
+</div></div>
 ===References===
 # '''OlympiAD:''' Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [https://doi.org/10.1056/NEJMoa1706450 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28578601 PubMed] NCT02000622
@@ Line 88: / Line 88: @@
 # '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
 ## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
 ==Carboplatin monotherapy {{#subobject:16h4a8|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:ujsx06|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 107: / Line 106: @@
 |}
 ''<sup>1</sup>Reported efficacy is based on subgroup analysis.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 '''21-day cycle for 6 to 8 cycles'''
+</div></div>
 ===References===
 # '''TNT:''' Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. Epub 2018 Apr 30. [https://www.nature.com/articles/s41591-018-0009-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372067/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29713086 PubMed] NCT00532727
 ==Carboplatin & Paclitaxel (CP) {{#subobject:842252|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:f16cn0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 132: / Line 130: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Confirmed deleterious germline BRCA1 or BRCA2 mutation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 '''21-day cycles'''
+</div></div>
 ===References===
 #'''BROCADE3:''' Diéras V, Han HS, Kaufman B, Wildiers H, Friedlander M, Ayoub JP, Puhalla SL, Bondarenko I, Campone M, Jakobsen EH, Jalving M, Oprean C, Palácová M, Park YH, Shparyk Y, Yañez E, Khandelwal N, Kundu MG, Dudley M, Ratajczak CK, Maag D, Arun BK. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Oct;21(10):1269-1282. Epub 2020 Aug 27. [https://doi.org/10.1016/s1470-2045(20)30447-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32861273 PubMed] NCT02163694
 ==Docetaxel monotherapy {{#subobject:3e34a8|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:71bf06|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 161: / Line 160: @@
 |}
 ''<sup>1</sup>Reported efficacy is based on subgroup analysis.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycle for 6 to 8 cycles'''
+</div></div>
 ===References===
 # '''TNT:''' Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. Epub 2018 Apr 30. [https://www.nature.com/articles/s41591-018-0009-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372067/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29713086 PubMed] NCT00532727
 ==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:25ef0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 192: / Line 190: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *EMBRACA: Germline BRCA1 or BRCA2 mutation
 *OlympiAD: Confirmed deleterious or suspected deleterious germline BRCA mutation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====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'''
+</div></div>
 ===References===
 # '''OlympiAD:''' Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [https://doi.org/10.1056/NEJMoa1706450 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28578601 PubMed] NCT02000622
@@ Line 205: / Line 205: @@
 # '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
 ## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
 ==Gemcitabine monotherapy {{#subobject:af0915|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:11b425|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 223: / Line 222: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Germline BRCA1 or BRCA2 mutation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 '''21-day cycles'''
+</div></div>
 ===References===
 # '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
 ## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
 ==Olaparib monotherapy {{#subobject:a019cd|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 100 mg twice per day {{#subobject:31ed8c|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 247: / Line 247: @@
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Olaparib (Lynparza)]] 100 mg PO twice per day
 '''Continued indefinitely'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 300 mg twice per day {{#subobject:3b0774|Variant=1}}===
 {| class="wikitable sortable" style="color:white; background-color:#404040"
@@ Line 267: / Line 268: @@
 |2014-2015
 |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
-|1. [[#Capecitabine_monotherapy|Capecitabine]]<br>2. [[#Eribulin_monotherapy|Eribulin]]<br> 3. [[#Vinorelbine_monotherapy|Vinorelbine]]
+|1a. [[#Capecitabine_monotherapy|Capecitabine]]<br>1b. [[#Eribulin_monotherapy|Eribulin]]<br>1c. [[#Vinorelbine_monotherapy|Vinorelbine]]
 |style="background-color:#1a9850"|Superior PFS <br>Median PFS: 7.0 mo vs 4.2 mo <br>(HR 0.58, 95% CI 0.43-0.80)
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Confirmed deleterious or suspected deleterious germline BRCA mutation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Olaparib (Lynparza)]] 300 mg PO twice per day
 '''Continued indefinitely'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #3, 400 mg twice per day {{#subobject:31cf8c|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
@@ Line 293: / Line 297: @@
 |-
 |}
-''Patients in Study 42 had germline BRCA1/2 mutations and had progressed after at least three lines of treatment for metastatic disease.''
+''Note: Patients in Study 42 had germline BRCA1/2 mutations and had progressed after at least three lines of treatment for metastatic disease.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Olaparib (Lynparza)]] 400 mg PO twice per day
 '''Continued indefinitely'''
+</div></div>
 ===References===
 # '''KU36-44:''' Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):235-44. Epub 2010 Jul 6. [https://doi.org/10.1016/S0140-6736(10)60892-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20609467 PubMed] NCT00494234
@@ Line 307: / Line 311: @@
 ==Talazoparib monotherapy {{#subobject:bb55eb|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:06a5b4|Variant=1}}===
 {| class="wikitable" style="color:white; background-color:#404040"
@@ Line 323: / Line 327: @@
 |2013-2017
 | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
-|Physician's choice of:<br> 1. [[#Capecitabine_monotherapy|Capecitabine]]<br>2. [[#Eribulin_monotherapy|Eribulin]]<br> 3. [[#Gemcitabine_monotherapy|Gemcitabine]]<br> 4. [[#Vinorelbine_monotherapy|Vinorelbine]]
+|Physician's choice of:<br>1a. [[#Capecitabine_monotherapy|Capecitabine]]<br>1b. [[#Eribulin_monotherapy|Eribulin]]<br>1c. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>1d. [[#Vinorelbine_monotherapy|Vinorelbine]]
 | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 8.6 vs 5.6 mo<br>(HR 0.54, 95% CI 0.41-0.71)
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Germline BRCA1 or BRCA2 mutation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Talazoparib (Talzenna)]] 1 mg PO once per day
 '''Continued indefinitely'''
+</div></div>
 ===References===
 # '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
 ## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
 ==Vinorelbine monotherapy {{#subobject:5c104c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 2 out of 3 weeks {{#subobject:7321fd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 355: / Line 360: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Confirmed deleterious or suspected deleterious germline BRCA mutation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 '''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, weekly {{#subobject:bjab1fd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
@@ Line 377: / Line 385: @@
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
 *Germline BRCA1 or BRCA2 mutation
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV over 6 to 10 minutes once per day on days 1, 8, 15
 '''21-day cycles'''
+</div></div>
 ===References===
 # '''OlympiAD:''' Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. [https://doi.org/10.1056/NEJMoa1706450 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28578601 PubMed] NCT02000622
@@ Line 388: / Line 399: @@
 # '''EMBRACA:''' Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. [https://doi.org/10.1056/NEJMoa1802905 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30110579 PubMed] NCT01945775
 ## '''Update:''' Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. [https://doi.org/10.1016/j.annonc.2020.08.2098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32828825 PubMed]
 =Additional resources=
 *[[Breast cancer BRCA1 & BRCA2 genetic testing]]
 *[https://oncomx.org/searchview/?gene=BRCA1 OncoMX -- BRCA1]
 *[https://oncomx.org/searchview/?gene=BRCA2 OncoMX -- BRCA2]
 [[Category:Breast cancer regimens]]
 [[Category:Biomarker-specific pages]]
 [[Category:Malignant breast neoplasm]]

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

Revision as of 12:31, 22 October 2022

Guidelines

ASCO

ESMO

Adjuvant therapy

Olaparib monotherapy

Regimen

Preceding treatment

Targeted therapy

References

Advanced or metastatic disease, subsequent lines of therapy

Capecitabine monotherapy

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Carboplatin monotherapy

Regimen

Chemotherapy

References

Carboplatin & Paclitaxel (CP)

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Docetaxel monotherapy

Regimen

Chemotherapy

References

Eribulin monotherapy

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Gemcitabine monotherapy

Regimen

Biomarker eligibility criteria

Chemotherapy

References

Olaparib monotherapy

Regimen variant #1, 100 mg twice per day

Targeted therapy

Regimen variant #2, 300 mg twice per day

Biomarker eligibility criteria

Targeted therapy

Regimen variant #3, 400 mg twice per day

Targeted therapy

References

Talazoparib monotherapy

Regimen

Biomarker eligibility criteria

Targeted therapy

References

Vinorelbine monotherapy

Regimen variant #1, 2 out of 3 weeks

Biomarker eligibility criteria

Chemotherapy

Regimen variant #2, weekly

Biomarker eligibility criteria

Chemotherapy

References

Additional resources

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