Breast cancer, CNS metastases
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| Section editor | |
|---|---|
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H. Deepika Fernandes, MD, FACP Virginia G. Piper Cancer Care Network Comprehensive Breast Center of Arizona Scottsdale, AZ, USA |
10 regimens on this page
5 variants on this page
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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 PubMed
- 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 PubMed
- 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 PubMed
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
To be completed
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 PubMed 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 PubMed NCT02915744
Gemcitabine monotherapy
Regimen
To be completed
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 PubMed 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 |
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 PubMed NCT02915744
Paclitaxel monotherapy, weekly
Regimen
To be completed
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 PubMed NCT02915744
nab-Paclitaxel monotherapy
Regimen
To be completed
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 PubMed NCT02915744
Vinorelbine monotherapy
Regimen
To be completed
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 PubMed 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 contains dosing details in abstract PubMed 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 contains dosing details in abstract PubMed 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 PubMed 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 contains dosing details in abstract PubMed 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 | Superior 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 contains dosing details in manuscript PubMed 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 PubMed