Breast cancer, HER2-low

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Note: these are regimens tested in biomarker-specific populations, please see the main breast cancer page for other regimens.
*Regimens for HER2 positive breast cancer are here.
*Regimens for ER/HER2 co-expressing ("double positive") breast cancer are here.
*Regimens for CNS metastases are here.
Last updated on TBA:TBA regimens on this page
TBA variants on this page
=Adjuvant therapy, sequential regimens=
==AC-T==
AC-T: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel)
===Regimen variant #1, weekly paclitaxel===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fehrenbacher et al. 2019 (NSABP B-47)	2011-2015 	Phase 3 (C)	1a. AC-TH1b. ddAC-TH1c. TCH	Did not meet primary endpoint of IDFSIDFS60: 89.2% vs 89.8%(HR 1.02, 95% CI 0.80-1.32)
====Biomarker eligibility criteria====
*HER2 IHC of 1+ or 2+ with FISH ratio less than 2 or HER2 gene copy number less than 4
====Preceding treatment====
*Surgery
====Chemotherapy, AC portion (cycles 1 to 4)====
*Doxorubicin (Adriamycin) 60 mg/m2 IV over 5 to 15 minutes once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV over 30 to 60 minutes once on day 1
====Chemotherapy, T portion (cycles 5 to 16)====
*Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 4 cycles, then 7-day cycle for 12 cycles (AC x 4; T x 12)
===References===
# NSABP B-47: Fehrenbacher L, Cecchini RS, Geyer CE Jr, Rastogi P, Costantino JP, Atkins JN, Crown JP, Polikoff J, Boileau JF, Provencher L, Stokoe C, Moore TD, Robidoux A, Flynn PJ, Borges VF, Albain KS, Swain SM, Paik S, Mamounas EP, Wolmark N. NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2. J Clin Oncol. 2020 Feb 10;38(5):444-453. Epub 2019 Dec 10. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01275677
==ddAC-T==
ddAC-T: dose-dense Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fehrenbacher et al. 2019 (NSABP B-47)	2011-2015 	Phase 3 (C)	1a. AC-TH1b. ddAC-TH1c. TCH	Did not meet primary endpoint of IDFSIDFS60: 89.2% vs 89.8%(HR 1.02, 95% CI 0.80-1.32)
Note: Fehrenbacher et al. 2019 did not explicitly describe the use of filgrastim, but it is typically used for the dose-dense portion of this regimen.
====Biomarker eligibility criteria====
*HER2 IHC of 1+ or 2+ with FISH ratio less than 2 or HER2 gene copy number less than 4
====Preceding treatment====
*Surgery
====Chemotherapy, ddAC portion (cycles 1 to 4)====
*Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
====Supportive therapy, ddAC portion (cycles 1 to 4)====
*Filgrastim (Neupogen) 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
====Chemotherapy, T portion (cycles 5 to 16)====
*Paclitaxel (Taxol) 80 mg/m2 IV once on day 1
14-day cycle for 4 cycles, then 7-day cycle for 12 cycles (AC x 4; T x 12)
===References===
# NSABP B-47: Fehrenbacher L, Cecchini RS, Geyer CE Jr, Rastogi P, Costantino JP, Atkins JN, Crown JP, Polikoff J, Boileau JF, Provencher L, Stokoe C, Moore TD, Robidoux A, Flynn PJ, Borges VF, Albain KS, Swain SM, Paik S, Mamounas EP, Wolmark N. NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2. J Clin Oncol. 2020 Feb 10;38(5):444-453. Epub 2019 Dec 10. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01275677
=Adjuvant chemotherapy=
==Cyclophosphamide & Docetaxel (TC)==
TC: Taxotere (Docetaxel) & Cyclophosphamide
DC: Docetaxel & Cyclophosphamide
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fehrenbacher et al. 2019 (NSABP B-47)	2011-2015 	Phase 3 (C)	1a. AC-TH1b. ddAC-TH1c. TCH	Did not meet primary endpoint of IDFSIDFS60: 89.2% vs 89.8%(HR 1.02, 95% CI 0.80-1.32)
====Biomarker eligibility criteria====
*HER2 IHC of 1+ or 2+ with FISH ratio less than 2 or HER2 gene copy number less than 4
====Preceding treatment====
*Surgery
====Chemotherapy====
*Docetaxel (Taxotere) 75 mg/m2 IV once on day 1 
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===References===
# NSABP B-47: Fehrenbacher L, Cecchini RS, Geyer CE Jr, Rastogi P, Costantino JP, Atkins JN, Crown JP, Polikoff J, Boileau JF, Provencher L, Stokoe C, Moore TD, Robidoux A, Flynn PJ, Borges VF, Albain KS, Swain SM, Paik S, Mamounas EP, Wolmark N. NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2. J Clin Oncol. 2020 Feb 10;38(5):444-453. Epub 2019 Dec 10. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01275677
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=Metastatic disease, subsequent lines of chemotherapy=
==Capecitabine monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Modi et al. 2022 (DESTINY-Breast04) 	2018-2021 	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS1Median PFS: 5.4 vs 10.1 mo(HR 1.96, 95% CI 1.56-2.50)Shorter OS2Median OS: 16.8 vs 23.4 mo(HR 1.56, 95% CI 1.19-2.04)
Bardia et al. 2024 (DESTINY-Breast06)	2020-08-20 to 2024-03-18	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS (primary endpoint)Median PFS: 8.1 vs 13.2 mo(HR 1.61, 95% CI 1.35-1.96)
1Reported efficacy for DESTINY-Breast04 is for the hormone-receptor positive subgroup.
2Reported efficacy for DESTINY-Breast04 is for all enrolled patients.
====Prior treatment criteria====
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
*DESTINY-Breast06: 1+ lines of endocrine therapy, no prior chemotherapy for metastatic disease
====Biomarker eligibility criteria====
*HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
====Chemotherapy====
*Capecitabine (Xeloda) 1000 to 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycles
===References===
# DESTINY-Breast04: Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03734029
# DESTINY-Breast06: Bardia A, Hu X, Dent R, Yonemori K, Barrios CH, O'Shaughnessy JA, Wildiers H, Pierga JY, Zhang Q, Saura C, Biganzoli L, Sohn J, Im SA, Lévy C, Jacot W, Begbie N, Ke J, Patel G, Curigliano G; DESTINY-Breast06 Trial Investigators. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med. 2024 Dec 5;391(22):2110-2122. Epub 2024 Sep 15. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04494425
==Eribulin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Modi et al. 2022 (DESTINY-Breast04)	2018-2021 	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS1Median PFS: 5.4 vs 10.1 mo(HR 1.96, 95% CI 1.56-2.50)Shorter OS2Median OS: 16.8 vs 23.4 mo(HR 1.56, 95% CI 1.19-2.04)
1Reported efficacy is for the hormone-receptor positive subgroup.
2Reported efficacy is for all enrolled patients.
====Prior treatment criteria====
*Exposure to 1 to 2 lines of chemotherapy for metastatic disease
====Biomarker eligibility criteria====
*HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
====Chemotherapy====
*Eribulin (Halaven) 1.4 mg/m2 IV over 2 to 5 minutes once per day on days 1 & 8
21-day cycles
===References===
# DESTINY-Breast04: Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03734029
==Gemcitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Modi et al. 2022 (DESTINY-Breast04)	2018-2021 	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS1Median PFS: 5.4 vs 10.1 mo(HR 1.96, 95% CI 1.56-2.50)Shorter OS2Median OS: 16.8 vs 23.4 mo(HR 1.56, 95% CI 1.19-2.04)
1Reported efficacy is for the hormone-receptor positive subgroup.
2Reported efficacy is for all enrolled patients.
====Prior treatment criteria====
*Exposure to 1 to 2 lines of chemotherapy for metastatic disease
====Biomarker eligibility criteria====
*HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
====Chemotherapy====
*Gemcitabine (Gemzar) 800 to 1200 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
===References===
# DESTINY-Breast04: Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03734029
==Paclitaxel monotherapy, weekly==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Modi et al. 2022 (DESTINY-Breast04) 	2018-2021 	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS1Median PFS: 5.4 vs 10.1 mo(HR 1.96, 95% CI 1.56-2.50)Shorter OS2Median OS: 16.8 vs 23.4 mo(HR 1.56, 95% CI 1.19-2.04)
Bardia et al. 2024 (DESTINY-Breast06)	2020-08-20 to 2024-03-18	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS (primary endpoint)Median PFS: 8.1 vs 13.2 mo(HR 1.61, 95% CI 1.35-1.96)
1Reported efficacy for DESTINY-Breast04 is for the hormone-receptor positive subgroup.
2Reported efficacy for DESTINY-Breast04 is for all enrolled patients.
====Prior treatment criteria====
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
*DESTINY-Breast06: 1+ lines of endocrine therapy, no prior chemotherapy for metastatic disease
====Biomarker eligibility criteria====
*HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
====Chemotherapy====
*Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once on day 1
7-day cycles
===References===
# DESTINY-Breast04: Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03734029
# DESTINY-Breast06: Bardia A, Hu X, Dent R, Yonemori K, Barrios CH, O'Shaughnessy JA, Wildiers H, Pierga JY, Zhang Q, Saura C, Biganzoli L, Sohn J, Im SA, Lévy C, Jacot W, Begbie N, Ke J, Patel G, Curigliano G; DESTINY-Breast06 Trial Investigators. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med. 2024 Dec 5;391(22):2110-2122. Epub 2024 Sep 15. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04494425
==Paclitaxel monotherapy, q3wk==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Modi et al. 2022 (DESTINY-Breast04)	2018-2021 	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS1Median PFS: 5.4 vs 10.1 mo(HR 1.96, 95% CI 1.56-2.50)Shorter OS2Median OS: 16.8 vs 23.4 mo(HR 1.56, 95% CI 1.19-2.04)
1Reported efficacy is for the hormone-receptor positive subgroup.
2Reported efficacy is for all enrolled patients.
====Prior treatment criteria====
*Exposure to 1 to 2 lines of chemotherapy for metastatic disease
====Biomarker eligibility criteria====
*HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
====Chemotherapy====
*Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
21-day cycles
===References===
# DESTINY-Breast04: Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03734029
==nab-Paclitaxel monotherapy==
===Regimen variant #1, 3 weeks out of 4, 100 mg/m2===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Modi et al. 2022 (DESTINY-Breast04) 	2018-2021 	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS1Median PFS: 5.4 vs 10.1 mo(HR 1.96, 95% CI 1.56-2.50)Shorter OS2Median OS: 16.8 vs 23.4 mo(HR 1.56, 95% CI 1.19-2.04)
Bardia et al. 2024 (DESTINY-Breast06)	2020-08-20 to 2024-03-18	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS (primary endpoint)Median PFS: 8.1 vs 13.2 mo(HR 1.61, 95% CI 1.35-1.96)
1Reported efficacy for DESTINY-Breast04 is for the hormone-receptor positive subgroup.
2Reported efficacy for DESTINY-Breast04 is for all enrolled patients.
Note: This was the lower bound of dosing in DESTINY-Breast04.
====Prior treatment criteria====
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
*DESTINY-Breast06: 1+ lines of endocrine therapy, no prior chemotherapy for metastatic disease
====Biomarker eligibility criteria====
*HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
====Chemotherapy====
*Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===Regimen variant #2, 3 weeks out of 4, 125 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Modi et al. 2022 (DESTINY-Breast04)	2018-2021 	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS1Median PFS: 5.4 vs 10.1 mo(HR 1.96, 95% CI 1.56-2.50)Shorter OS2Median OS: 16.8 vs 23.4 mo(HR 1.56, 95% CI 1.19-2.04)
1Reported efficacy is for the hormone-receptor positive subgroup.
2Reported efficacy is for all enrolled patients.
Note: This was the upper bound of dosing in DESTINY-Breast04.
====Prior treatment criteria====
*Exposure to 1 to 2 lines of chemotherapy for metastatic disease
====Biomarker eligibility criteria====
*HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
====Chemotherapy====
*Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===Regimen variant #3, q3wk===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Modi et al. 2022 (DESTINY-Breast04)	2018-2021 	Phase 3 (C)	Trastuzumab deruxtecan	Shorter PFS1Median PFS: 5.4 vs 10.1 mo(HR 1.96, 95% CI 1.56-2.50)Shorter OS2Median OS: 16.8 vs 23.4 mo(HR 1.56, 95% CI 1.19-2.04)
1Reported efficacy is for the hormone-receptor positive subgroup.
2Reported efficacy is for all enrolled patients.
====Prior treatment criteria====
*Exposure to 1 to 2 lines of chemotherapy for metastatic disease
====Biomarker eligibility criteria====
*HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
====Chemotherapy====
*Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV over 30 minutes once on day 1
21-day cycles
===References===
# DESTINY-Breast04: Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03734029
# DESTINY-Breast06: Bardia A, Hu X, Dent R, Yonemori K, Barrios CH, O'Shaughnessy JA, Wildiers H, Pierga JY, Zhang Q, Saura C, Biganzoli L, Sohn J, Im SA, Lévy C, Jacot W, Begbie N, Ke J, Patel G, Curigliano G; DESTINY-Breast06 Trial Investigators. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med. 2024 Dec 5;391(22):2110-2122. Epub 2024 Sep 15. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04494425
==Trastuzumab deruxtecan monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Modi et al. 2022 (DESTINY-Breast04) 	2018-2021 	Phase 3 (E-RT-switch-ooc)	Investigator's choice of:1a. Capecitabine1b. Eribulin1c. Gemcitabine1d. Paclitaxel; weekly1e. Paclitaxel; q3wk1f. nab-Paclitaxel	Longer PFS1 (primary endpoint)Median PFS: 10.1 vs 5.4 mo(HR 0.51, 95% CI 0.40-0.64)Longer OS2 (secondary endpoint)Median OS: 23.4 vs 16.8 mo(HR 0.64, 95% CI 0.49-0.84)	Higher rate of pneumonitis
Bardia et al. 2024 (DESTINY-Breast06)	2020-08-20 to 2024-03-18	Phase 3 (E-RT-switch-ooc)	Investigator's choice of:1a. Capecitabine1b. Paclitaxel; weekly1c. nab-Paclitaxel 	Longer PFS (primary endpoint)Median PFS: 13.2 vs 8.1 mo(HR 0.62, 95% CI 0.51-0.74) 	Higher rate of pneumonitis
1Reported efficacy for DESTINY-Breast04 is for the hormone-receptor positive subgroup.
2Reported efficacy for DESTINY-Breast04 is for all enrolled patients.
Note: eribulin was the most commonly used comparator regimen.
====Prior treatment criteria====
*DESTINY-Breast04: Exposure to 1 to 2 lines of chemotherapy for metastatic disease
*DESTINY-Breast06: 1+ lines of endocrine therapy, no prior chemotherapy for metastatic disease
====Biomarker eligibility criteria====
*HER2 IHC 1+ or HER2 IHC 2+ and FISH negative
====Antibody-drug conjugate therapy====
*Trastuzumab deruxtecan (Enhertu) 5.4 mg/kg IV once on day 1
21-day cycles
===References===
# DESTINY-Breast04: Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. Epub 2022 Jun 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03734029
# DESTINY-Breast06: Bardia A, Hu X, Dent R, Yonemori K, Barrios CH, O'Shaughnessy JA, Wildiers H, Pierga JY, Zhang Q, Saura C, Biganzoli L, Sohn J, Im SA, Lévy C, Jacot W, Begbie N, Ke J, Patel G, Curigliano G; DESTINY-Breast06 Trial Investigators. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med. 2024 Dec 5;391(22):2110-2122. Epub 2024 Sep 15. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04494425
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