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Section editor transclusions 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.

0 regimens on this page 0 variants on this page

Neoadjuvant chemotherapy

Trastuzumab emtansine monotherapy

T-DM1: Trastuzumab-DM1 (Trastuzumab emtansine)

Regimen

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

Antibody-drug conjugate therapy

Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1

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 (Paclitaxel), unless the patient had pCR in which case adjuvant therapy was optional

References

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 dosing details in manuscript PubMed NCT01817452

T-DM1 & ET

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

Regimen

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

Antibody-drug conjugate therapy

Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1

Endocrine therapy

One of the following:
- Premenopausal women: Tamoxifen (Nolvadex) recommended
- GnRH analogs were also allowed
- Postmenopausal women: Aromatase inhibitor recommended

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 (Paclitaxel), unless the patient had pCR in which case adjuvant therapy was optional

References

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 dosing details in manuscript PubMed NCT01817452

Trastuzumab & ET

Trastuzumab & ET: Trastuzumab & Endocrine Therapy

Regimen

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

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1

Endocrine therapy

Endocrine therapy by the following criteria:
- Premenopausal women: Tamoxifen (Nolvadex) recommended
  - GnRH analogs were also allowed
- Postmenopausal women: Aromatase inhibitor recommended

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 (Paclitaxel), unless the patient had pCR in which case adjuvant therapy was optional

References

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 dosing details in manuscript PubMed NCT01817452

Adjuvant therapy

Anastrozole monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (eMonarcHER)	2021-ongoing	Phase 3 (C)	ET & Abemaciclib	In progress

Preceding treatment

HER2-targeted therapy

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day

Continued for up to 10 years

References

eMonarcHER: NCT04752332

Metastatic disease, first-line therapy

Anastrozole monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kaufman et al. 2009 (TAnDEM)	2001-2004	Phase 3 (C)	Anastrozole & Trastuzumab	Inferior PFS

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day

28-day cycles

References

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 dosing details in abstract PubMed NCT00022672

Anastrozole & Trastuzumab

Regimen variant #1, weekly trastuzumab

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kaufman et al. 2009 (TAnDEM)	2001-2004	Phase 3 (E-esc)	Anastrozole	Superior PFS Median PFS: 4.8 vs 2.4 mo (HR 0.63, 95% CI 0.47-0.84)

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day

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 3 (C)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Did not meet secondary endpoint of PFS
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	4. Anastrozole, Lapatinib, Trastuzumab 5. Exemestane, Lapatinib, Trastuzumab 6. Lapatinib, Letrozole, Trastuzumab	Inferior PFS
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (E-switch-ooc)	1. TH (Paclitaxel) 2. TH (Docetaxel) 3. VH; IV 4. VH; PO 5. XH	Non-Inferior PFS Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09)

Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for anastrozole.

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

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day

21-day cycles

References

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 dosing details in abstract PubMed NCT00022672
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 dosing details in manuscript PubMed NCT01160211
SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol PubMed NCT01950182

Anastrozole, Lapatinib, Trastuzumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Not reported
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	4. Anastrozole & Trastuzumab 5. Exemestane & Trastuzumab 6. Letrozole & Trastuzumab	Superior PFS Median PFS: 11 vs 5.6 mo (HR 0.62, 95% CI 0.45-0.88)

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

Targeted therapy

Lapatinib (Tykerb) 1000 mg PO once per day
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

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day

21-day cycles

References

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 dosing details in manuscript PubMed NCT01160211

Exemestane & Trastuzumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Did not meet secondary endpoint of PFS
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	4. Anastrozole, Lapatinib, Trastuzumab 5. Exemestane, Lapatinib, Trastuzumab 6. Lapatinib, Letrozole, Trastuzumab	Inferior PFS
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (E-switch-ooc)	1. TH (Paclitaxel) 2. TH (Docetaxel) 3. VH; IV 4. VH; PO 5. XH	Non-Inferior PFS Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09)

Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for exemestane.

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

Endocrine therapy

Exemestane (Aromasin) 1 mg PO once per day

21-day cycles

References

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 dosing details in manuscript PubMed NCT01160211
SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol PubMed NCT01950182

Exemestane, Lapatinib, Trastuzumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Not reported
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	4. Anastrozole & Trastuzumab 5. Exemestane & Trastuzumab 6. Letrozole & Trastuzumab	Superior PFS Median PFS: 11 vs 5.6 mo (HR 0.62, 95% CI 0.45-0.88)

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

Targeted therapy

Lapatinib (Tykerb) 1000 mg PO once per day
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

Endocrine therapy

Exemestane (Aromasin) 25 mg PO once per day

21-day cycles

References

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 dosing details in manuscript PubMed NCT01160211

Lapatinib & Letrozole

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2009 (EGF30008)	2003-2006	Phase 3 (E-RT-esc)	Letrozole	Seems to have superior PFS Median PFS: 8.2 vs 3 mo (HR 0.71, 95% CI 0.53-0.96)

Targeted therapy

Lapatinib (Tykerb) 1500 mg PO once per day

Endocrine therapy

Letrozole (Femara) 2.5 mg PO once per day

Continued indefinitely

References

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 dosing details in abstract PubMed NCT00073528

Lapatinib, Letrozole, Trastuzumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Not reported
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	4. Anastrozole & Trastuzumab 5. Exemestane & Trastuzumab 6. Letrozole & Trastuzumab	Superior PFS Median PFS: 11 vs 5.6 mo (HR 0.62, 95% CI 0.45-0.88)

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

Targeted therapy

Lapatinib (Tykerb) 1000 mg PO once per day
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

Endocrine therapy

Letrozole (Femara) 2.5 mg PO once per day

21-day cycles

References

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 dosing details in manuscript PubMed NCT01160211

Letrozole monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2009 (EGF30008)	2003-2006	Phase 3 (C)	Lapatinib & Letrozole	Seems to have inferior PFS

Endocrine therapy

Letrozole (Femara) 2.5 mg PO once per day

28-day cycles

References

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 dosing details in abstract PubMed NCT00073528

Letrozole & Trastuzumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Did not meet secondary endpoint of PFS
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	4. Anastrozole, Lapatinib, Trastuzumab 5. Exemestane, Lapatinib, Trastuzumab 6. Lapatinib, Letrozole, Trastuzumab	Inferior PFS
Hua et al. 2022 (SYSUCC-002)	2013-2019	Phase 3 (E-switch-ooc)	1. TH (Paclitaxel) 2. TH (Docetaxel) 3. VH; IV 4. VH; PO 5. XH	Non-Inferior PFS Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09)

Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. does not contain dosing instructions for letrozole.

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

Endocrine therapy

Letrozole (Femara) 2.5 mg PO once per day

21-day cycles

References

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 dosing details in manuscript PubMed NCT01160211
SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol PubMed NCT01950182

@@ Line 3: / Line 3: @@
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 </div>
-{{#lst:Section editor transclusions|endo}}
+{{#lst:Section editor transclusions|breast}}
-''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Neuroendocrine tumor - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br>
+<big>'''Note: these are regimens tested in patients with hormone receptor-positive, HER2-positive breast cancer. Please see the [[breast cancer|main breast cancer page]], [[Breast cancer, ER-positive|ER+ breast cancer page]], and [[Breast cancer, HER2-positive|HER2+ breast cancer page]] for other regimens.'''</big>
-<big>Note: This page is now exclusively focused on those tumors commonly called carcinoids, which may or may not be associated with the carcinoid syndrome; there are now separate pages for '''[[pancreatic NET]]''' and other endocrine cancers. Neuroendocrine tumors of unknown primary and poorly differentiated (high-grade) neuroendocrine tumors are usually treated with a '''[[small cell lung cancer]]''' regimen.</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 12: / Line 11: @@
 |}
 {{TOC limit|limit=3}}
-=Guidelines=
+=Neoadjuvant chemotherapy=
-==CommNETS/NANETS==
+==Trastuzumab emtansine monotherapy {{#subobject:ef98f0|Regimen=1}}==
-*'''2020:''' Singh et al. [https://doi.org/10.1016/j.jtho.2020.06.021 Commonwealth Neuroendocrine Tumour Research Collaboration and the North American Neuroendocrine Tumor Society Guidelines for the Diagnosis and Management of Patients With Lung Neuroendocrine Tumors: An International Collaborative Endorsement and Update of the 2015 European Neuroendocrine Tumor Society Expert Consensus Guidelines]
+T-DM1: '''<u>T</u>'''rastuzumab-'''<u>DM1</u>''' (Trastuzumab emtansine)
-==[http://www.esmo.org/ ESMO]==
-*'''2021:''' Baudin et al. [https://doi.org/10.1016/j.annonc.2021.01.003 Lung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
-===Older===
-*'''2012:''' Öberg et al. [https://www.esmo.org/Guidelines/Endocrine-and-Neuroendocrine-Cancers/Neuroendocrine-Bronchial-and-Thymic-Tumours Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.]
-*'''2012:''' Öberg et al. [http://annonc.oxfordjournals.org/content/23/suppl_7/vii124.full.pdf+html Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.] [https://pubmed.ncbi.nlm.nih.gov/22997445 PubMed]
-==NANETS==
-*'''2017:''' Strosberg et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5642985/ The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors]
-===Older===
-*'''2013:''' Kunz et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4304762/ Consensus Guidelines for the Management and Treatment of Neuroendocrine Tumors]
-==[https://www.nccn.org/ NCCN]==
-*[https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf NCCN Guidelines - Neuroendocrine Tumors]
-=All lines of therapy=
-==Everolimus monotherapy {{#subobject:99989f|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:4ef82e|Variant=1}}===
+===Regimen {{#subobject:91b517|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
+!style="width: 20%"|Study
-!style="width: 15%"|Years of enrollment
+!style="width: 20%"|Years of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
+!style="width: 20%"|Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|rowspan=2|[https://doi.org/10.1200/JCO.2016.71.9815 Harbeck et al. 2017 (WGSG ADAPT)]
+|rowspan=2|2012-2015
+|rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
+|1. [[#T-DM1_.26_ET|T-DM1 & ET]]
+|style="background-color:#d0d0d0"|Not reported
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063317/ Yao et al. 2015 (RADIANT-4)]
+|2. [[#Trastuzumab_.26_ET|Trastuzumab & ET]]
-|2012-2013
+|style="background-color:#1a9850"|Superior pCR rate
-|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
-|[[Neuroendocrine_tumor_-_null_regimens#Placebo|Placebo]]
-| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: NYR vs NYR<br>(HR 0.64, 95% CI 0.40-1.05)
-|style="background-color:#eeee01"|Equivalent HRQoL
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Antibody-drug conjugate therapy====
-*[[Everolimus (Afinitor)]] 10 mg PO once per day
+*[[Trastuzumab emtansine (Kadcyla)]] 3.6 mg/kg IV once on day 1
-'''Continued indefinitely'''
+'''21-day cycle for 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]], then [[#Paclitaxel_.26_Trastuzumab_.28TH.29_2|TH (Paclitaxel)]], unless the patient had pCR in which case adjuvant therapy was optional
 </div></div>
 ===References===
-# '''RADIANT-4:''' Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, Tomasek J, Raderer M, Lahner H, Voi M, Pacaud LB, Rouyrre N, Sachs C, Valle JW, Fave GD, Van Cutsem E, Tesselaar M, Shimada Y, Oh DY, Strosberg J, Kulke MH, Pavel ME; RAD001 in Advanced Neuroendocrine Tumours Fourth Trial (RADIANT-4) Study Group. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016 Mar 5;387(10022):968-977. Epub 2015 Dec 17. [https://doi.org/10.1016/S0140-6736(15)00817-X link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063317/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26703889 PubMed] NCT01524783
+# '''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. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681 PubMed] NCT01817452
-## '''HRQoL analysis:''' Pavel ME, Singh S, Strosberg JR, Bubuteishvili-Pacaud L, Degtyarev E, Neary MP, Carnaghi C, Tomasek J, Wolin E, Raderer M, Lahner H, Valle JW, Pommier R, Van Cutsem E, Tesselaar MET, Fave GD, Buzzoni R, Hunger M, Eriksson J, Cella D, Ricci JF, Fazio N, Kulke MH, Yao JC. Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1411-1422. Epub 2017 Aug 30. [https://doi.org/10.1016/S1470-2045(17)30471-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28838862 PubMed]
+==T-DM1 & ET {{#subobject:207386|Regimen=1}}==
-==Everolimus & Octreotide {{#subobject:d69a17|Regimen=1}}==
+T-DM1 & ET: '''<u>T</u>'''rastuzumab-DM1 (Trastuzumab emtansine) & '''<u>E</u>'''ndocrine '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:9dd15|Variant=1}}===
+===Regimen {{#subobject:b28ce1|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653122/ Yao et al. 2008]
-|2005-2006
-| style="background-color:#91cf61" |Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Everolimus (Afinitor)]] 5 mg PO once per day
-====Endocrine therapy====
-*[[Octreotide LAR (Sandostatin LAR)]] 30 mg IM once on day 1
-'''28-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:867317|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 83: / Line 55: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653122/ Yao et al. 2008]
+|rowspan=2|[https://doi.org/10.1200/JCO.2016.71.9815 Harbeck et al. 2017 (WGSG ADAPT)]
-|2005-2006
+|rowspan=2|2012-2015
-| style="background-color:#91cf61" |Phase 2
+|rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
-| style="background-color:#d3d3d3" |
+|1. [[#Trastuzumab_emtansine_monotherapy|T-DM1]]
-| style="background-color:#d3d3d3" |
+|style="background-color:#d0d0d0"|Not reported
 |-
-|[https://doi.org/10.1016/S0140-6736(11)61742-X Pavel et al. 2011 (RADIANT-2)]
+|2. [[#Trastuzumab_.26_ET|Trastuzumab & ET]]
-|2007-2010
+|style="background-color:#1a9850"|Superior pCR rate
-|style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[#Octreotide_LAR_monotherapy|Octreotide LAR]]
-|style="background-color:#91cf60"|Seems to have superior PFS<br>Median PFS: 16.4 vs 11.3 mo<br>(HR 0.77, 95% CI 0.59-1.00)
 |-
 |}
-''Note: RADIANT-2 did not meet its primary endpoint, based on a pre-specified p-value cutoff of 0.0246.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Antibody-drug conjugate therapy====
-*[[Everolimus (Afinitor)]] 10 mg PO once per day
+*[[Trastuzumab emtansine (Kadcyla)]] 3.6 mg/kg IV once on day 1
 ====Endocrine therapy====
-*[[Octreotide LAR (Sandostatin LAR)]] 30 mg IM once on day 1
+*One of the following:
-'''28-day cycles'''
+**Premenopausal women: [[Tamoxifen (Nolvadex)]] recommended
+**[[:Category:GnRH_agonists|GnRH analogs]] were also allowed
+**Postmenopausal women: [[:Category:Aromatase inhibitors|Aromatase inhibitor]] recommended
+'''21-day cycle for 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]], then [[#Paclitaxel_.26_Trastuzumab_.28TH.29_2|TH (Paclitaxel)]], unless the patient had pCR in which case adjuvant therapy was optional
 </div></div>
 ===References===
-# Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol. 2008 Sep 10;26(26):4311-8. [https://doi.org/10.1200/jco.2008.16.7858 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653122/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18779618 PubMed]
+# '''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. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681 PubMed] NCT01817452
-# '''RADIANT-2:''' Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011 Dec 10;378(9808):2005-12. Epub 2011 Nov 25. [https://doi.org/10.1016/S0140-6736(11)61742-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22119496 PubMed] NCT00412061
+==Trastuzumab & ET {{#subobject:b9d62c|Regimen=1}}==
-## '''Update:''' Pavel ME, Baudin E, Öberg KE, Hainsworth JD, Voi M, Rouyrre N, Peeters M, Gross DJ, Yao JC. Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study. Ann Oncol. 2017 Jul 1;28(7):1569-1575. [https://doi.org/10.1093/annonc/mdx193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28444114 PubMed]
+Trastuzumab & ET: Trastuzumab & '''<u>E</u>'''ndocrine '''<u>T</u>'''herapy
-==Fluorouracil & Streptozocin {{#subobject:bd8397|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:d34072|Variant=1}}===
+===Regimen {{#subobject:d0233|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 118: / Line 92: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1984.2.11.1255 Engstrom et al. 1984 (ECOG E5275)]
+|[https://doi.org/10.1200/JCO.2016.71.9815 Harbeck et al. 2017 (WGSG ADAPT)]
-|1976-1981
+|2012-2015
-|style="background-color:#1a9851"|Phase 3 (E-esc)
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
-|[[#Doxorubicin_monotherapy_88|Doxorubicin]]
+|1. [[#Trastuzumab_emtansine_monotherapy|T-DM1]]<br> 2. [[#T-DM1_.26_ET|T-DM1 & ET]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/OS
+|style="background-color:#d73027"|Inferior pCR rate
-|-
-|[https://doi.org/10.1200/JCO.2005.03.616 Sun et al. 2005]
-|1981-1990
-|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-|[[#Doxorubicin_.26_Fluorouracil_88|Doxorubicin & Fluorouracil]]
-| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Targeted therapy====
-*[[Fluorouracil (5-FU)]]
+*[[Trastuzumab (Herceptin)]] as follows:
-*[[Streptozocin (Zanosar)]]
+**Cycle 1: 8 mg/kg IV once on day 1
+**Cycles 2 to 4: 6 mg/kg IV once on day 1
+====Endocrine therapy====
+*Endocrine therapy by the following criteria:
+**Premenopausal women: [[Tamoxifen (Nolvadex)]] recommended
+***[[:Category:GnRH_agonists|GnRH analogs]] were also allowed
+**Postmenopausal women: [[:Category:Aromatase inhibitors|Aromatase inhibitor]] recommended
+'''21-day cycle for 4 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]], then [[#Paclitaxel_.26_Trastuzumab_.28TH.29_2|TH (Paclitaxel)]], unless the patient had pCR in which case adjuvant therapy was optional
 </div></div>
 ===References===
-# '''ECOG E5275:''' Engstrom PF, Lavin PT, Moertel CG, Folsch E, Douglass HO Jr. Streptozocin plus fluorouracil versus doxorubicin therapy for metastatic carcinoid tumor. J Clin Oncol. 1984 Nov;2(11):1255-9. [https://doi.org/10.1200/JCO.1984.2.11.1255 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6238136 PubMed]
+# '''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. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681 PubMed] NCT01817452
-# '''ECOG E1281:''' Sun W, Lipsitz S, Catalano P, Mailliard JA, Haller DG; [[Study_Groups#ECOG|ECOG]]. Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol. 2005 Aug 1;23(22):4897-904. [https://doi.org/10.1200/JCO.2005.03.616 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16051944 PubMed]
+=Adjuvant therapy=
-==Interferon alfa-2b monotherapy {{#subobject:557a2f|Regimen=1}}==
+==Anastrozole monotherapy {{#subobject:79h35|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:a0cb2f|Variant=1}}===
+===Regimen {{#subobject:gav33c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 149: / Line 128: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/NEJM198307213090301 Oberg et al. 1983]
+|Awaiting publication (eMonarcHER)
-|NR
+|2021-ongoing
-| style="background-color:#ffffbe" |Non-randomized, <20 pts
+|style="background-color:#1a9851"|Phase 3 (C)
-| style="background-color:#d3d3d3" |
+|[[#ET_.26_Abemaciclib_88|ET & Abemaciclib]]
-| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |In progress
-|-
-|rowspan=2|[https://doi.org/10.1200/jco.2003.12.142 Faiss et al. 2003]
-|rowspan=2|1995-1998
-|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-de-esc)
-|1. [[#Lanreotide_monotherapy|Lanreotide]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR at 12 mo
-|-
-|2. [[#Lanreotide_.26_Interferon_alfa-2b|Lanreotide & Interferon alfa-2b]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR at 12 mo
 |-
 |}
-''Treatment details are from Faiss et al. 2003.''
+<div class="toccolours" style="background-color:#cbd5e8">
-====Immunotherapy====
+====Preceding treatment====
-*[[Interferon alfa-2b (Intron-A)]] 5,000,000 units SC once per day, 3 times per week
+*[[Regimen_classes#Anti-HER2-based_regimen|HER2-targeted therapy]]
-'''Continued indefinitely'''
 </div>
-<div class="toccolours" style="background-color:#cbd5e7">
+<div class="toccolours" style="background-color:#b3e2cd">
-====Subsequent treatment====
+====Endocrine therapy====
-*Patients who progressed on monotherapy then received [[#Lanreotide_.26_Interferon_alfa-2b|lanreotide & interferon alfa]]
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day
+'''Continued for up to 10 years'''
 </div></div>
 ===References===
-# Oberg K, Funa K, Alm G. Effects of leukocyte interferon on clinical symptoms and hormone levels in patients with mid-gut carcinoid tumors and carcinoid syndrome. N Engl J Med. 1983 Jul 21;309(3):129-33. [https://doi.org/10.1056/NEJM198307213090301 linkt to original article] [https://pubmed.ncbi.nlm.nih.gov/6191217 PubMed]
+#'''eMonarcHER:''' NCT04752332
-# Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B; International Lanreotide and Interferon Alfa Study Group. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003 Jul 15;21(14):2689-96. [https://doi.org/10.1200/jco.2003.12.142 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12860945 PubMed]
+=Metastatic disease, first-line therapy=
-==Lanreotide monotherapy {{#subobject:c44a4e|Regimen=1}}==
+==Anastrozole monotherapy {{#subobject:796bb|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:171ae2|Variant=1}}===
+===Regimen {{#subobject:bd033c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 187: / Line 157: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=2|[https://doi.org/10.1200/jco.2003.12.142 Faiss et al. 2003]
+|[https://doi.org/10.1200/JCO.2008.20.6847 Kaufman et al. 2009 (TAnDEM)]
-|rowspan=2|1995-1998
+|2001-2004
-|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-de-esc)
+|style="background-color:#1a9851"|Phase 3 (C)
-|1. [[#Interferon_alfa-2b_monotherapy|Interferon alfa-2b]]
+|[[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR at 12 mo
+| style="background-color:#d73027" |Inferior PFS
-|-
-|2. [[#Lanreotide_.26_Interferon_alfa-2b|Lanreotide & Interferon alfa-2b]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR at 12 mo
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
-*[[Lanreotide (Somatuline)]] 1 mg SC three times per day
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day
-'''Continued indefinitely'''
+'''28-day cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Faiss et al. 2003, patients who progressed on monotherapy: [[#Lanreotide_.26_Interferon_alfa-2b|Lanreotide & interferon alfa]]
 </div></div>
 ===References===
-# Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B; International Lanreotide and Interferon Alfa Study Group. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003 Jul 15;21(14):2689-96. [https://doi.org/10.1200/jco.2003.12.142 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12860945 PubMed]
+# '''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. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786670 PubMed] NCT00022672
-==Lanreotide LAR monotherapy {{#subobject:c4ugjc|Regimen=1}}==
+==Anastrozole & Trastuzumab {{#subobject:8077ad|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:741ae2|Variant=1}}===
+===Regimen variant #1, weekly trastuzumab {{#subobject:e6f8f0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 218: / Line 181: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.4158/ep151172.or Vinik et al. 2016 (ELECT)]
+|[https://doi.org/10.1200/JCO.2008.20.6847 Kaufman et al. 2009 (TAnDEM)]
-|NR in abstract
+|2001-2004
-| style="background-color:#1a9851"|Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[#Placebo_88|Placebo]]
+|[[#Anastrozole_monotherapy_2|Anastrozole]]
-| style="background-color:#1a9850" |Decreased need for short-acting octreotide rescue
+| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4.8 vs 2.4 mo<br>(HR 0.63, 95% CI 0.47-0.84)
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
-*[[Lanreotide LAR (Somatuline Depot)]] 120 mg IM once on day 1
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day
-'''28-day cycle for 4 cycles'''
+====Targeted therapy====
-</div></div>
+*[[Trastuzumab (Herceptin)]] as follows:
-===References===
+**Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
-# '''ELECT:''' Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA; ELECT Study Group. Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment (ELECT): A Randomized, Double-Blind, Placebo-Controlled Trial. Endocr Pract. 2016 Sep;22(9):1068-80. Epub 2016 May 23. [https://doi.org/10.4158/ep151172.or link to original article] [https://pubmed.ncbi.nlm.nih.gov/27214300/ PubMed] NCT00774930
+**Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22
-==Lanreotide & Interferon alfa-2b {{#subobject:ce8ef2|Regimen=1}}==
+'''28-day cycles'''
+</div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:87b3d6|Variant=1}}===
+===Regimen variant #2, q3wk trastuzumab {{#subobject:ugibx4|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 242: / Line 206: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=2|[https://doi.org/10.1200/jco.2003.12.142 Faiss et al. 2003]
+|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)]
-|rowspan=2|1995-1998
+|rowspan=2|2011-2016
-|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
-|1. [[#Interferon_alfa-2b_monotherapy|Interferon alfa-2b]]
+|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br> 3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR at 12 mo
+| style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
+|-
+|4. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br> 5. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br> 6. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]]
+| style="background-color:#d73027" |Inferior PFS
 |-
-|2. [[#Lanreotide_monotherapy|Lanreotide]]
+|[https://doi.org/10.1158/1078-0432.ccr-21-3435 Hua et al. 2022 (SYSUCC-002)]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR at 12 mo
+|2013-2019
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+|1. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_88|TH (Paclitaxel)]]<br>2. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>3. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; IV<br>4. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; PO<br>5. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
+| style="background-color:#eeee01" |Non-Inferior PFS<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
 |-
 |}
+''Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for anastrozole.''
 <div class="toccolours" style="background-color:#b3e2cd">
+====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
 ====Endocrine therapy====
-*[[Lanreotide (Somatuline)]] 1 mg SC three times per day
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day
-====Immunotherapy====
+'''21-day cycles'''
-*[[Interferon alfa-2b (Intron-A)]] 5,000,000 units SC once per day, 3 times per week
 </div></div>
 ===References===
-# Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B; International Lanreotide and Interferon Alfa Study Group. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003 Jul 15;21(14):2689-96. [https://doi.org/10.1200/jco.2003.12.142 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12860945 PubMed]
+# '''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. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786670 PubMed] NCT00022672
-==Lutetium Lu 177 dotatate & Octreotide LAR {{#subobject:eca71b|Regimen=1}}==
+<!--- # '''RETRACTED:''' 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: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
-{| class="wikitable" style="color:white; background-color:#404040"
+# '''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. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
-|<small>'''FDA-recommended dose'''</small>
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] NCT01950182
-|-
+==Anastrozole, Lapatinib, Trastuzumab {{#subobject:gg0dbc|Regimen=1}}==
-|}
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:9df044|Variant=1}}===
+===Regimen {{#subobject:ug8a84|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 274: / Line 247: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1158/1078-0432.ccr-16-2743 Brabander et al. 2017 (ERASMUS)]
+|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)]
-|2000-2015
+|rowspan=2|2011-2016
-| style="background-color:#ffffbe" |Case series (RT)
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
-| style="background-color:#d3d3d3" |
+|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
-| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |Not reported
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895095/ Strosberg et al. 2017 (NETTER-1)]
+|4. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br> 5. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br> 6. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]
-|2012-2016
+| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88)
-|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
-|[[#Octreotide_LAR_monotherapy|Octreotide LAR]]
-|style="background-color:#1a9850"|Superior PFS<br>Median PFS: NYR vs 8.4 mo<br>(HR 0.21, 95% CI 0.13-0.33)
 |-
 |}
-''This is the FDA-recommended dose.''
+''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.''
-====Radioconjugate therapy====
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Lutetium Lu 177 dotatate (Lutathera)]] 7.4 GBq (200 mCi) IV over 30 minutes once on day 1
+====Targeted therapy====
-'''8-week cycle for 4 cycles'''
+*[[Lapatinib (Tykerb)]] 1000 mg PO once per day
+*[[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
 ====Endocrine therapy====
-*[[Octreotide LAR (Sandostatin LAR)]] as follows:
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day
-**Cycles 1 to 4: 30 mg IM once on day 2, '''given approximately 24 hours after lutetium Lu 177 dotatate'''
+'''21-day cycles'''
-**Cycle 5 onwards: 30 mg IM once on day 1
-'''8-week cycle for 4 cycles, then monthly cycles'''
 </div></div>
 ===References===
-# '''NETTER-1:''' Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 trial of (177)Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. [https://doi.org/10.1056/NEJMoa1607427 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895095/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28076709 PubMed] NCT01578239
+<!--- # '''RETRACTED:''' 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: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
-## '''Update:''' Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP; NETTER-1 investigators. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1752-1763. Epub 2021 Nov 15. [https://doi.org/10.1016/s1470-2045(21)00572-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34793718/ PubMed]
+# '''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. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
-# '''ERASMUS:''' Brabander T, van der Zwan WA, Teunissen JJM, Kam BLR, Feelders RA, de Herder WW, van Eijck CHJ, Franssen GJH, Krenning EP, Kwekkeboom DJ. Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors. Clin Cancer Res. 2017 Aug 15;23(16):4617-4624. Epub 2017 Apr 20. [https://doi.org/10.1158/1078-0432.ccr-16-2743 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28428192/ PubMed]
+==Exemestane & Trastuzumab {{#subobject:ugjxbc|Regimen=1}}==
-==Octreotide monotherapy {{#subobject:1b6b74|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:eb529b|Variant=1}}===
+===Regimen {{#subobject:1yga84|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 20%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://annonc.oxfordjournals.org/content/15/6/966.long Oberg et al. 2004]
+|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)]
-|style="background-color:#ffffbe"|Consensus guideline
+|rowspan=2|2011-2016
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
+| style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 |-
-|}
+|4. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br> 5. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br> 6. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]]
-<div class="toccolours" style="background-color:#b3e2cd">
+| style="background-color:#d73027" |Inferior PFS
-====Endocrine therapy====
-*[[Octreotide (Sandostatin)]] 0.1 to 0.5 mg SC given 2 to four times per day, with dose increased by doubling the dose every 3 to 4 days as needed to control symptoms
-**"A reasonable starting dose is" 0.15 mg SC three times per day
-'''Continued indefinitely'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:29f57|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1056/NEJM198609113151102 Kvols et al. 1986]
+|[https://doi.org/10.1158/1078-0432.ccr-21-3435 Hua et al. 2022 (SYSUCC-002)]
-|style="background-color:#91cf61"|Phase 2
+|2013-2019
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+|1. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_88|TH (Paclitaxel)]]<br>2. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>3. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; IV<br>4. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; PO<br>5. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
+| style="background-color:#eeee01" |Non-Inferior PFS<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
 |-
 |}
+''Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for exemestane.''
 <div class="toccolours" style="background-color:#b3e2cd">
+====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
 ====Endocrine therapy====
-*[[Octreotide (Sandostatin)]] 0.15 mg SC twice per day on days 1 & 2, then 0.15 mg SC three times per day from day 3 onward
+*[[Exemestane (Aromasin)]] 1 mg PO once per day
-'''Continued indefinitely'''
+'''21-day cycles'''
-</div></div><br>
+</div></div>
+===References===
+<!--- # '''RETRACTED:''' 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: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
+# '''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. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] NCT01950182
+==Exemestane, Lapatinib, Trastuzumab {{#subobject:hh0dbc|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3 {{#subobject:a531c2|Variant=1}}===
+===Regimen {{#subobject:258gja|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 342: / Line 321: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1002/bjs.4149 Kölby et al. 2003]
+|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)]
-|1991-1998
+|rowspan=2|2011-2016
-|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[#Octreotide_.26_Interferon_alfa|Octreotide & Interferon alfa]]
+|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
-|style="background-color:#d73027"|Inferior TTP
+| style="background-color:#d3d3d3" |Not reported
 |-
-|}
+|4. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br> 5. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br> 6. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]
-<div class="toccolours" style="background-color:#b3e2cd">
+| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88)
-====Endocrine therapy====
-*[[Octreotide (Sandostatin)]] 0.1 mg SC twice per day
-**Patients with persistent carcinoid symptoms could receive increased doses up to 0.2 mg SC three times per day
-'''Continued indefinitely'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, low-dose {{#subobject:512195|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.3109/02841869309083916 Janson & Oberg 1993]
-|style="background-color:#91cf61"|Non-randomized
 |-
 |}
+''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.''
 <div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Lapatinib (Tykerb)]] 1000 mg PO once per day
+*[[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
 ====Endocrine therapy====
-*[[Octreotide (Sandostatin)]] 0.05 mg SC twice per day
+*[[Exemestane (Aromasin)]] 25 mg PO once per day
-'''Continued indefinitely'''
+'''21-day cycles'''
 </div></div>
 ===References===
-# Kvols LK, Moertel CG, O'Connell MJ, Schutt AJ, Rubin J, Hahn RG. Treatment of the malignant carcinoid syndrome: evaluation of a long-acting somatostatin analogue. N Engl J Med. 1986 Sep 11;315(11):663-6. [https://doi.org/10.1056/NEJM198609113151102 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2427948 PubMed]
+<!--- # '''RETRACTED:''' 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: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
-# Janson ET, Oberg K. Long-term management of the carcinoid syndrome: treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol. 1993;32(2):225-9. [https://doi.org/10.3109/02841869309083916 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7686765 PubMed]
+# '''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. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
-# Kölby L, Persson G, Franzén S, Ahrén B. Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg. 2003 Jun;90(6):687-93. [https://doi.org/10.1002/bjs.4149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12808615 PubMed]
+==Lapatinib & Letrozole {{#subobject:5fba83|Regimen=1}}==
-# '''Review:''' Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, Ruszniewski P, Woltering EA, Wiedenmann B. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004 Jun;15(6):966-73. [https://doi.org/10.1093/annonc/mdh216 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15151956 PubMed]
-==Octreotide LAR monotherapy {{#subobject:3fde03|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 30 mg {{#subobject:38d708|Variant=1}}===
+===Regimen {{#subobject:879969|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 385: / Line 355: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2009.22.8510 Rinke et al. 2009 (PROMID)]
+|[https://doi.org/10.1200/JCO.2009.23.3734 Johnston et al. 2009 (EGF30008)]
-|2001-2008
+|2003-2006
-|style="background-color:#1a9851"|Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
-|[[Neuroendocrine_tumor_-_null_regimens#Placebo|Placebo]]
+|[[#Letrozole_monotherapy_3|Letrozole]]
-|style="background-color:#1a9850"|Superior TTP<br>Median TTP: 14.3 vs 6 mo<br>(HR 0.34, 95% CI 0.20-0.59)
+| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 8.2 vs 3 mo<br>(HR 0.71, 95% CI 0.53-0.96)
-|-
-|[https://doi.org/10.1016/S0140-6736(11)61742-X Pavel et al. 2011 (RADIANT-2)]
-|2007-2010
-|style="background-color:#1a9851"|Phase 3 (C)
-|[[#Everolimus_.26_Octreotide|Octreotide LAR & Everolimus]]
-|style="background-color:#fc8d59"|Seems to have inferior PFS
 |-
 |}
-''Note: RADIANT-2 did not meet its primary endpoint, based on a pre-specified p-value cutoff of 0.0246.''
 <div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Lapatinib (Tykerb)]] 1500 mg PO once per day
 ====Endocrine therapy====
-*[[Octreotide LAR (Sandostatin LAR)]] 30 mg IM once on day 1, with potentially higher doses if needed for symptom control
+*[[Letrozole (Femara)]] 2.5 mg PO once per day
-'''28-day cycles'''
+'''Continued indefinitely'''
-</div></div><br>
+</div></div>
+===References===
+# '''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. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786658 PubMed] NCT00073528
+==Lapatinib, Letrozole, Trastuzumab {{#subobject:ee0dbc|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 40 mg {{#subobject:7c7215a|Variant=1}}===
+===Regimen {{#subobject:251384|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 413: / Line 381: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562767/ Wolin et al. 2015 (CSOM230C2303)]
+|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)]
-|2008-2012
+|rowspan=2|2011-2016
-|style="background-color:#1a9851"|Phase 3 (C)
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[#Pasireotide_LAR_77|Pasireotide LAR]]
+|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of symptom control
+| style="background-color:#d3d3d3" |Not reported
+|-
+|4. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br> 5. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br> 6. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]
+| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88)
 |-
 |}
+''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.''
 <div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Lapatinib (Tykerb)]] 1000 mg PO once per day
+*[[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
 ====Endocrine therapy====
-*[[Octreotide LAR (Sandostatin LAR)]] 40 mg IM once on day 1
+*[[Letrozole (Femara)]] 2.5 mg PO once per day
-'''28-day cycles'''
+'''21-day cycles'''
-</div></div><br>
+</div></div>
+===References===
+<!--- # '''RETRACTED:''' 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: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
+# '''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. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
+==Letrozole monotherapy {{#subobject:75d541|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 60 mg {{#subobject:7c826a|Variant=1}}===
+===Regimen {{#subobject:d7ef99|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 434: / Line 415: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895095/ Strosberg et al. 2017 (NETTER-1)]
+|[https://doi.org/10.1200/JCO.2009.23.3734 Johnston et al. 2009 (EGF30008)]
-|2012-2016
+|2003-2006
 |style="background-color:#1a9851"|Phase 3 (C)
-|[[#Lutetium_Lu_177_dotatate_.26_Octreotide_LAR|Lutetium Lu 177 dotatate & Octreotide LAR]]
+|[[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
-|style="background-color:#d73027"|Inferior PFS
+| style="background-color:#fc8d59" |Seems to have inferior PFS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
-*[[Octreotide LAR (Sandostatin LAR)]] 60 mg IM once on day 1
+*[[Letrozole (Femara)]] 2.5 mg PO once per day
 '''28-day cycles'''
 </div></div>
 ===References===
-# '''Review:''' Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, Ruszniewski P, Woltering EA, Wiedenmann B. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004 Jun;15(6):966-73. [https://doi.org/10.1093/annonc/mdh216 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15151956 PubMed]
+# '''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. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786658 PubMed] NCT00073528
-# '''PROMID:''' Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Bläker M, Harder J, Arnold C, Gress T, Arnold R; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009 Oct 1;27(28):4656-63. Epub 2009 Aug 24. [https://doi.org/10.1200/jco.2009.22.8510 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19704057 PubMed] NCT00171873
+==Letrozole & Trastuzumab {{#subobject:8ugz41|Regimen=1}}==
-# '''RADIANT-2:''' Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011 Dec 10;378(9808):2005-12. Epub 2011 Nov 25. [https://doi.org/10.1016/S0140-6736(11)61742-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22119496 PubMed] NCT00412061
-## '''Update:''' Pavel ME, Baudin E, Öberg KE, Hainsworth JD, Voi M, Rouyrre N, Peeters M, Gross DJ, Yao JC. Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study. Ann Oncol. 2017 Jul 1;28(7):1569-1575. [https://doi.org/10.1093/annonc/mdx193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28444114 PubMed]
-# '''CSOM230C2303:''' Wolin EM, Jarzab B, Eriksson B, Walter T, Toumpanakis C, Morse MA, Tomassetti P, Weber MM, Fogelman DR, Ramage J, Poon D, Gadbaw B, Li J, Pasieka JL, Mahamat A, Swahn F, Newell-Price J, Mansoor W, Öberg K. Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. Drug Des Devel Ther. 2015 Sep 3;9:5075-86. [https://www.dovepress.com/phase-iii-study-of-pasireotide-long-acting-release-in-patients-with-me-peer-reviewed-article-DDDT link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562767/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26366058 PubMed] NCT00690430
-# '''NETTER-1:''' Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 trial of (177)Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. [https://doi.org/10.1056/NEJMoa1607427 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895095/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28076709 PubMed] NCT01578239
-## '''Update:''' Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP; NETTER-1 investigators. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1752-1763. Epub 2021 Nov 15. [https://doi.org/10.1016/s1470-2045(21)00572-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34793718/ PubMed]
-==Octreotide & Interferon alfa {{#subobject:dea906|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:b5051e|Variant=1}}===
+===Regimen {{#subobject:6cq284|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 464: / Line 439: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1002/bjs.4149 Kölby et al. 2003]
+|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)]
-|1991-1998
+|rowspan=2|2011-2016
-|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
-|[[#Octreotide_monotherapy|Octreotide LAR]]
+|1. [[#Anastrozole_.26_Lapatinib_99|Anastrozole & Lapatinib]]<br> 2. [[#Exemestane_.26_Lapatinib_99|Exemestane & Lapatinib]]<br>3. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]]
-|style="background-color:#1a9850"|Superior TTP
+| style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455764/ Yao et al. 2017 (SWOG S0518)]
+|4. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br> 5. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br> 6. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]]
-|2007-2012
+| style="background-color:#d73027" |Inferior PFS
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Octreotide_.26_Bevacizumab_99|Octreotide & Bevacizumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
-|}
+|[https://doi.org/10.1158/1078-0432.ccr-21-3435 Hua et al. 2022 (SYSUCC-002)]
-''Kölby et al. 2003 did not specifically say whether [[Interferon alfa-2b (Intron-A)]] or [[Interferon alfa-2a (Roferon-A)]] was used.''
+|2013-2019
-====Endocrine therapy====
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
-*[[Octreotide (Sandostatin)]] 0.1 mg SC twice per day
+|1. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_88|TH (Paclitaxel)]]<br>2. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>3. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; IV<br>4. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_88|VH]]; PO<br>5. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]]
-**Patients with persistent carcinoid symptoms could receive increased doses up to 0.2 mg SC three times per day
+| style="background-color:#eeee01" |Non-Inferior PFS<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09)
-====Immunotherapy====
-*[[Interferon alfa-2b (Intron-A)]] 3,000,000 units (route not specified) once per day, 3 days per week
-**Increased as needed based on symptoms up to 5,000,000 units (route not specified) once per day, 5 days per week
-</div></div>
-===References===
-# Janson ET, Oberg K. Long-term management of the carcinoid syndrome: treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol. 1993;32(2):225-9. [https://doi.org/10.3109/02841869309083916 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7686765 PubMed]
-# Kölby L, Persson G, Franzén S, Ahrén B. Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg. 2003 Jun;90(6):687-93. [https://doi.org/10.1002/bjs.4149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12808615 PubMed]
-# '''SWOG S0518:''' Yao JC, Guthrie KA, Moran C, Strosberg JR, Kulke MH, Chan JA, LoConte N, McWilliams RR, Wolin EM, Mattar B, McDonough S, Chen H, Blanke CD, Hochster HS. Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518. J Clin Oncol. 2017 May 20;35(15):1695-1703. Epub 2017 Apr 6. [https://doi.org/10.1200/JCO.2016.70.4072 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455764/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28384065 PubMed] NCT00569127
-==Temozolomide monotherapy {{#subobject:5db4de|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:7e3904|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[http://clincancerres.aacrjournals.org/content/13/10/2986.long Ekeblad et al. 2007]
-| style="background-color:#ffffbe" |Retrospective
 |-
 |}
+''Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. does not contain dosing instructions for letrozole.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Targeted therapy====
-*[[Temozolomide (Temodar)]] as follows:
+*[[Trastuzumab (Herceptin)]] as follows:
-**Cycle 1: 100 or 150 mg/m<sup>2</sup> PO once per day on days 1 to 5
+**Cycle 1: 8 mg/kg IV once on day 1
-**Cycle 2 onwards: increased as tolerated up to 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
-====Supportive therapy====
+====Endocrine therapy====
-*[[Tropisetron (Navoban)]] (dose/route/schedule not specified) routinely used as an antiemetic
+*[[Letrozole (Femara)]] 2.5 mg PO once per day
-'''28-day cycles'''
+'''21-day cycles'''
 </div></div>
 ===References===
-# '''Retrospective:''' Ekeblad S, Sundin A, Janson ET, Welin S, Granberg D, Kindmark H, Dunder K, Kozlovacki G, Orlefors H, Sigurd M, Oberg K, Eriksson B, Skogseid B. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res. 2007 May 15;13(10):2986-91. [http://clincancerres.aacrjournals.org/content/13/10/2986.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17505000 PubMed]
+<!--- # '''RETRACTED:''' 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: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528 PubMed] -->
-[[Category:Neuroendocrine tumor regimens]]
+# '''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. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287 PubMed] NCT01160211
-[[Category:Disease-specific pages]]
+# '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] NCT01950182
-[[Category:Endocrine cancers]]
+[[Category:Breast cancer regimens]]
+[[Category:Biomarker-specific pages]]
+[[Category:Malignant breast neoplasm]]

Difference between revisions of "Staging page"

Revision as of 16:56, 15 October 2022

Neoadjuvant chemotherapy

Trastuzumab emtansine monotherapy

Regimen

Antibody-drug conjugate therapy

Subsequent treatment

References

T-DM1 & ET

Regimen

Antibody-drug conjugate therapy

Endocrine therapy

Subsequent treatment

References

Trastuzumab & ET

Regimen

Targeted therapy

Endocrine therapy

Subsequent treatment

References

Adjuvant therapy

Anastrozole monotherapy

Regimen

Preceding treatment

Endocrine therapy

References

Metastatic disease, first-line therapy

Anastrozole monotherapy

Regimen

Endocrine therapy

References

Anastrozole & Trastuzumab

Regimen variant #1, weekly trastuzumab

Endocrine therapy

Targeted therapy

Regimen variant #2, q3wk trastuzumab

Targeted therapy

Endocrine therapy

References

Anastrozole, Lapatinib, Trastuzumab

Regimen

Targeted therapy

Endocrine therapy

References

Exemestane & Trastuzumab

Regimen

Targeted therapy

Endocrine therapy

References

Exemestane, Lapatinib, Trastuzumab

Regimen

Targeted therapy

Endocrine therapy

References

Lapatinib & Letrozole

Regimen

Targeted therapy

Endocrine therapy

References

Lapatinib, Letrozole, Trastuzumab

Regimen

Targeted therapy

Endocrine therapy

References

Letrozole monotherapy

Regimen

Endocrine therapy

References

Letrozole & Trastuzumab

Regimen

Targeted therapy

Endocrine therapy

References

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