Breast cancer, HER2-low
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| Section editor | |
|---|---|
 |
Gayathri Nagaraj, MD Loma Linda University Loma Linda, CA, USA |
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-TH 1b. ddAC-TH 1c. TCH |
Did not meet primary endpoint of IDFS IDFS60: 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
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 PubMed 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-TH 1b. ddAC-TH 1c. TCH |
Did not meet primary endpoint of IDFS IDFS60: 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
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 PubMed 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-TH 1b. ddAC-TH 1c. TCH |
Did not meet primary endpoint of IDFS IDFS60: 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
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 PubMed NCT01275677
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 PFS1 Median PFS: 5.4 vs 10.1 mo (HR 1.96, 95% CI 1.56-2.50) Shorter OS2 Median 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 PubMed 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 PubMed 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 PFS1 Median PFS: 5.4 vs 10.1 mo (HR 1.96, 95% CI 1.56-2.50) Shorter OS2 Median 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 PubMed 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 PFS1 Median PFS: 5.4 vs 10.1 mo (HR 1.96, 95% CI 1.56-2.50) Shorter OS2 Median 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 PubMed 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 PFS1 Median PFS: 5.4 vs 10.1 mo (HR 1.96, 95% CI 1.56-2.50) Shorter OS2 Median 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
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 PubMed 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 PubMed 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 PFS1 Median PFS: 5.4 vs 10.1 mo (HR 1.96, 95% CI 1.56-2.50) Shorter OS2 Median 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
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 PubMed 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 PFS1 Median PFS: 5.4 vs 10.1 mo (HR 1.96, 95% CI 1.56-2.50) Shorter OS2 Median 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 PFS1 Median PFS: 5.4 vs 10.1 mo (HR 1.96, 95% CI 1.56-2.50) Shorter OS2 Median 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 PFS1 Median PFS: 5.4 vs 10.1 mo (HR 1.96, 95% CI 1.56-2.50) Shorter OS2 Median 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 PubMed 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 PubMed 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. Capecitabine 1b. Eribulin 1c. Gemcitabine 1d. Paclitaxel; weekly 1e. Paclitaxel; q3wk 1f. 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-switch-ooc) | Investigator's choice of: 1a. Capecitabine 1b. Paclitaxel; weekly 1c. 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 PubMed 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 PubMed NCT04494425