Breast cancer, ER and HER2 co-expressing

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H. Deepika Fernandes, MD, FACP
University of North Dakota
Bismarck, ND

Note: these are regimens tested in patients with hormone receptor-positive, HER2-positive breast cancer. Please see the main breast cancer page, ER+ breast cancer page, and HER2+ breast cancer page for other regimens.

12 regimens on this page
13 variants on this page

Contents


Neoadjuvant chemotherapy

Ado-trastuzumab emtansine monotherapy

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T-DM1: Trastuzumab-DM1 (Ado-trastuzumab emtansine)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Harbeck et al. 2017 (WGSG ADAPT) 2012-2015 Randomized Phase II (E-switch-ic) 1. T-DM1 & ET Not reported
2. Trastuzumab & ET Superior pCR rate

Antibody-drug conjugate therapy

21-day cycle for 4 cycles

Subsequent treatment

  • Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of EC, then TH (Taxol), unless the patient had pCR in which case adjuvant therapy was optional

References

  1. WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains verified protocol PubMed NCT01817452

T-DM1 & ET

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T-DM1 & ET: Trastuzumab-DM1 (Ado-trastuzumab emtansine) & Endocrine Therapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Harbeck et al. 2017 (WGSG ADAPT) 2012-2015 Randomized Phase II (E-esc) 1. T-DM1 Not reported
2. Trastuzumab & ET Superior pCR rate

Antibody-drug conjugate therapy

Hormonotherapy

21-day cycle for 4 cycles

Subsequent treatment

  • Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of EC, then TH (Taxol), unless the patient had pCR in which case adjuvant therapy was optional

References

  1. WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains verified protocol PubMed NCT01817452

Trastuzumab & ET

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Trastuzumab & ET: Trastuzumab & Endocrine Therapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Harbeck et al. 2017 (WGSG ADAPT) 2012-2015 Randomized Phase II (C) 1. T-DM1
2. T-DM1 & ET
Inferior pCR rate

Targeted therapy

Hormonotherapy

21-day cycle for 4 cycles

Subsequent treatment

  • Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of EC, then TH (Taxol), unless the patient had pCR in which case adjuvant therapy was optional

References

  1. WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains verified protocol PubMed NCT01817452

Metastatic disease, first-line therapy

Anastrozole monotherapy

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kaufman et al. 2009 (TAnDEM) 2001-2004 Phase III (C) Anastrozole & Trastuzumab Inferior PFS

Hormonotherapy

28-day cycles

References

  1. TAnDEM: Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. link to original article contains protocol PubMed NCT00022672

Anastrozole & Trastuzumab

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Regimen variant #1, weekly trastuzumab

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kaufman et al. 2009 (TAnDEM) 2001-2004 Phase III (E-esc) Anastrozole Superior PFS

Hormonotherapy

Targeted therapy

  • Trastuzumab (Herceptin) as follows:
    • Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
    • Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22

28-day cycles

Regimen variant #2, q3wk trastuzumab

Study Years of enrollment Evidence Comparator Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE) 2011-2016 Phase III (C) 1. Anastrozole & Lapatinib
2. Exemestane & Lapatinib
3. Lapatinib & Letrozole
Not reported
4. Anastrozole, Lapatinib, Trastuzumab
5. Exemestane, Lapatinib, Trastuzumab
6. Lapatinib, Letrozole, Trastuzumab
Inferior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

Hormonotherapy

21-day cycles

References

  1. TAnDEM: Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. link to original article contains protocol PubMed NCT00022672
  2. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211

Anastrozole, Lapatinib, Trastuzumab

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE) 2011-2016 Phase III (E-esc) 1. Anastrozole & Lapatinib
2. Exemestane & Lapatinib
3. Lapatinib & Letrozole
Not reported
4. Anastrozole & Trastuzumab
5. Exemestane & Trastuzumab
6. Letrozole & Trastuzumab
Superior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

Hormonotherapy

21-day cycles

References

  1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211

Exemestane & Trastuzumab

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE) 2011-2016 Phase III (C) 1. Anastrozole & Lapatinib
2. Exemestane & Lapatinib
3. Lapatinib & Letrozole
Not reported
4. Anastrozole, Lapatinib, Trastuzumab
5. Exemestane, Lapatinib, Trastuzumab
6. Lapatinib, Letrozole, Trastuzumab
Inferior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

Hormonotherapy

21-day cycles

References

  1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211

Exemestane, Lapatinib, Trastuzumab

back to top

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE) 2011-2016 Phase III (E-esc) 1. Anastrozole & Lapatinib
2. Exemestane & Lapatinib
3. Lapatinib & Letrozole
Not reported
4. Anastrozole & Trastuzumab
5. Exemestane & Trastuzumab
6. Letrozole & Trastuzumab
Superior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

Hormonotherapy

21-day cycles

References

  1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211

Lapatinib & Letrozole

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Johnston et al. 2009 (EGF30008) 2003-2006 Phase III (E-RT-esc) Letrozole Seems to have superior PFS

Targeted therapy

Hormonotherapy

Continued indefinitely

References

  1. EGF30008: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. link to original article contains protocol PubMed NCT00073528

Lapatinib, Letrozole, Trastuzumab

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE) 2011-2016 Phase III (E-esc) 1. Anastrozole & Lapatinib
2. Exemestane & Lapatinib
3. Lapatinib & Letrozole
Not reported
4. Anastrozole & Trastuzumab
5. Exemestane & Trastuzumab
6. Letrozole & Trastuzumab
Superior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

Hormonotherapy

21-day cycles

References

  1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211

Letrozole monotherapy

back to top

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Johnston et al. 2009 (EGF30008) 2003-2006 Phase III (C) Lapatinib & Letrozole Seems to have inferior PFS

Hormonotherapy

28-day cycles

References

  1. EGF30008: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. link to original article contains protocol PubMed NCT00073528

Letrozole & Trastuzumab

back to top

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE) 2011-2016 Phase III (C) 1. Anastrozole & Lapatinib
2. Exemestane & Lapatinib
3. Lapatinib & Letrozole
Not reported
4. Anastrozole, Lapatinib, Trastuzumab
5. Exemestane, Lapatinib, Trastuzumab
6. Lapatinib, Letrozole, Trastuzumab
Inferior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

Hormonotherapy

21-day cycles

References

  1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211