Breast cancer, CNS metastases

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Last updated on 2024-07-23:13 regimens on this page
13 variants on this page
Note: these are studies of regimens tested in patients with breast cancer and CNS metastases, or subgroups of more general studies that focused on patients with CNS metastases. Please see the main breast cancer page for other 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==
*2022: Ramakrishna et al. Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases EuroPMC
**2018: Ramakrishna et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline update EuroPMC
**2014: Ramakrishna et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline link to PMC article EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Breast Cancer and NCCN Guidelines - Central Nervous System Cancers.
=Unselected, all lines of therapy=
==Docetaxel monotherapy==
D: Docetaxel
T: Taxotere (Docetaxel)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tripathy et al. 2022 (ATTAIN)	2017-2019 	Phase 3 (C)	Etirinotecan pegol	Did not meet primary endpoint of OS
To be completed
====Chemotherapy====
*Docetaxel (Taxotere)
===References===
# ATTAIN: Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. link to original article link to PMC article does not contain dosing details EuroPMC NCT02915744
==Eribulin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tripathy et al. 2022 (ATTAIN)	2017-2019 	Phase 3 (C)	Etirinotecan pegol	Did not meet primary endpoint of OS
====Chemotherapy====
*Eribulin (Halaven) 1.4 mg/m2 IV over 2 to 5 minutes once per day on days 1 & 8
21-day cycles
===References===
# ATTAIN: Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. link to original article link to PMC article does not contain dosing details EuroPMC NCT02915744
==Gemcitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tripathy et al. 2022 (ATTAIN)	2017-2019 	Phase 3 (C)	Etirinotecan pegol	Did not meet primary endpoint of OS
To be completed
====Chemotherapy====
*Gemcitabine (Gemzar)
===References===
# ATTAIN: Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. link to original article link to PMC article does not contain dosing details EuroPMC NCT02915744
==Ixabepilone monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tripathy et al. 2022 (ATTAIN)	2017-2019 	Phase 3 (C)	Etirinotecan pegol	Did not meet primary endpoint of OS
====Chemotherapy====
*Ixabepilone (Ixempra) 40 mg/m2 IV over 3 hours once on day 1
21-day cycles
===References===
# ATTAIN: Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. link to original article link to PMC article does not contain dosing details EuroPMC NCT02915744
==Paclitaxel monotherapy, weekly==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tripathy et al. 2022 (ATTAIN)	2017-2019 	Phase 3 (C)	Etirinotecan pegol	Did not meet primary endpoint of OS
To be completed
====Chemotherapy====
*Paclitaxel (Taxol)
===References===
# ATTAIN: Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. link to original article link to PMC article does not contain dosing details EuroPMC NCT02915744
==nab-Paclitaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tripathy et al. 2022 (ATTAIN)	2017-2019 	Phase 3 (C)	Etirinotecan pegol	Did not meet primary endpoint of OS
To be completed
====Chemotherapy====
*Paclitaxel, nanoparticle albumin-bound (Abraxane)
===References===
# ATTAIN: Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. link to original article link to PMC article does not contain dosing details EuroPMC NCT02915744
==Vinorelbine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tripathy et al. 2022 (ATTAIN)	2017-2019 	Phase 3 (C)	Etirinotecan pegol	Did not meet primary endpoint of OS
To be completed
====Chemotherapy====
*Vinorelbine (Navelbine)
===References===
# ATTAIN: Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052. link to original article link to PMC article does not contain dosing details EuroPMC NCT02915744
=HER2-positive, first-line therapy=
==Capecitabine & Lapatinib==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Pivot et al. 2015 (CEREBEL)	2009-2012 	Phase 3 (E-switch-ic)	Capecitabine & Trastuzumab	Did not meet primary endpoint of CNS metastases as first site of relapse
====Biomarker eligibility criteria====
*Gene: HER2 Positive
*Clinical Trial Eligibility: score > 2.2 by fluorescence in situ hybridization and/or 3+ amplification by immunohistochemistry or chromogenic/silver in situ hybridization
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
====Targeted therapy====
*Lapatinib (Tykerb) 1250 mg PO once per day on days 1 to 21
21-day cycles
===References===
#CEREBEL: Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00820222
==Capecitabine & Trastuzumab (XH)==
XH: Xeloda (Capecitabine) & Herceptin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Pivot et al. 2015 (CEREBEL)	2009-2012 	Phase 3 (C)	Capecitabine & Lapatanib	Did not meet primary endpoint of CNS metastases as first site of relapse
====Biomarker eligibility criteria====
*Gene HER2 Positive
*Clinical Trial Eligibility: score > 2.2 by fluorescence in situ hybridization and/or 3+ amplification by immunohistochemistry or chromogenic/silver in situ hybridization
====Chemotherapy====
*Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
====Targeted therapy====
*Trastuzumab (Herceptin) as follows:
**Cycle 1: 8 mg/kg IV once on day 1
**Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
===References===
#CEREBEL: Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00820222
=HER2-positive, subsequent lines of therapy=
==Capecitabine & Lapatinib==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Pivot et al. 2015 (CEREBEL)	2009-2012 	Phase 3 (E-switch-ic)	Capecitabine & Trastuzumab	Did not meet primary endpoint of CNS metastases as first site of relapse
====Biomarker eligibility criteria====
*Gene: HER2 Positive
*Clinical Trial Eligibility: score > 2.2 by fluorescence in situ hybridization and/or 3+ amplification by immunohistochemistry or chromogenic/silver in situ hybridization
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
====Targeted therapy====
*Lapatinib (Tykerb) 1250 mg PO once per day on days 1 to 21
21-day cycles
===References===
#CEREBEL: Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article EuroPMC NCT00820222
==Capecitabine & Trastuzumab (XH)==
XH: Xeloda (Capecitabine) & Herceptin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Pivot et al. 2015 (CEREBEL)	2009-2012 	Phase 3 (C)	Capecitabine & Lapatanib	Did not meet primary endpoint of CNS metastases as first site of relapse
====Biomarker eligibility criteria====
*Gene HER2 Positive
*Clinical Trial Eligibility: score > 2.2 by fluorescence in situ hybridization and/or 3+ amplification by immunohistochemistry or chromogenic/silver in situ hybridization
====Chemotherapy====
*Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
====Targeted therapy====
*Trastuzumab (Herceptin) as follows:
**Cycle 1: 8 mg/kg IV once on day 1
**Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
===References===
#CEREBEL: Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00820222
==Capecitabine & Trastuzumab (XH) & Tucatinib==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Murthy et al. 2019 (HER2CLIMB)	2016-2019 	Phase 3 (E-RT-esc)	XH 	Longer OS (secondary endpoint)Median OS: 21.9 vs 17.4 mo(HR 0.66, 95% CI 0.50-0.88)
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
====Targeted therapy====
*Tucatinib (Tukysa) 300 mg PO twice per day on days 1 to 21
*Trastuzumab (Herceptin) as follows:
**Cycle 1: 8 mg/kg IV once on day 1
**Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
===References===
# HER2CLIMB: Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):597-609. Epub 2019 Dec 11. Erratum in: N Engl J Med. 2020 Feb 6;382(6):586. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02614794
## Subgroup analysis: Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol. 2020 Aug 10;38(23):2610-2619. Epub 2020 May 29. link to original article link to PMC article EuroPMC
==Trastuzumab deruxtecan monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Cortés et al. 2022 (DESTINY-Breast03)	2018-2020 	Phase 3 (E-RT-switch-ic)	T-DM1 	Longer PFS1 (primary endpoint)Median PFS: 15 vs 3 mo(HR 0.25, 95% CI 0.13-0.45)
1Reported efficacy is based on the 2024 subgroup analysis of patients with brain metastases.
====Prior treatment criteria====
*DESTINY-Breast03: Trastuzumab and taxane
====Antibody-drug conjugate therapy====
*Trastuzumab deruxtecan (Enhertu) 5.4 mg/kg IV once on day 1
21-day cycles
===References===
# DESTINY-Breast03: Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03529110
##Update: Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, Chiu JWY, Xu B, Hamilton E, Madhusudan S, Iwata H, Altintas S, Henning JW, Curigliano G, Perez-Garcia JM, Kim SB, Petry V, Huang CS, Li W, Frenel JS, Antolin S, Yeo W, Bianchini G, Loi S, Tsurutani J, Egorov A, Liu Y, Cathcart J, Ashfaque S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023 Jan 14;401(10371):105-117. Epub 2022 Dec 7. link to original article EuroPMC
##PRO analysis: Curigliano G, Dunton K, Rosenlund M, Janek M, Cathcart J, Liu Y, Fasching PA, Iwata H. Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Ann Oncol. 2023 Jul;34(7):569-577. Epub 2023 May 12. link to original article EuroPMC
##Subgroup analysis: Hurvitz SA, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Egorov A, Liu Y, Cathcart J, Bako E, Tecson K, Verma S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024 May;9(5):102924. Epub 2024 Apr 24. link to original article link to PMC article EuroPMC
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