Trastuzumab-emtansine versus other anti-HER2 regimens in early or unresectable or metastatic HER2 positive breast cancer: systematic review and network meta-analysis

Authors

DOI:

https://doi.org/10.17843/rpmesp.2024.411.13351

Keywords:

HER2 Genes, Breast Cancer, Network Meta-Analysis, Systematic Review, Trastuzumab Emtansine

Abstract

Objective. We aimed to study the efficacy and safety of trastuzumab-emtansine (T-DM1) versus other anti-HER2
therapies in HER2+ breast cancer (BC). Materials and Methods. We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs). Our study focused on patients undergoing treatment for unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (mBC), which included regimens involving trastuzumab and taxanes. Additionally, we considered cases within the first 6 months of treatment for HER2+ early breast cancer (EBC). Results. A total of 23 RCTs and 41 reports were included in our analysis. LABC and mBC showed no statistically significant difference in any of the comparisons of T-DM1 versus the other anti-HER2+ therapies. When assessing progression-free survival (PFS), trastuzumab-deruxtecan (T-DXd) and PyroCap demonstrated greater efficacy compared to other treatments (Hazard Ratio [HR]: 3.57; 95% confidence interval [CI]: 2.75-4.63 and HR: 1.82; 95% CI: 1.35-2.44;
respectively), while T-DM1 alone exhibited superior effectiveness compared to LapCap (HR: 0.65; 95% CI: 0.55-0.77), TrasCap (HR: 0.65; 95% CI: 0.46-0.91), LapCapCitu (HR: 0.60; 95% CI: 0.33-1.10), Nera (HR: 0.55; 95% CI: 0.39-0.77), and Cap (HR: 0.37; 95% CI: 0.28-0.49). Conclusions. NMA allows a ranking based on the comparative efficacy and safety among the interventions available. Although superior to other schemes, T-DM1 showed a lower efficacy performance
in PFS and overall response rate and a trend towards worse overall survival than T-DXd.

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References

International Agency for Research on Cancer. World Health Organization [Internet]. [citado el 10 de febrero de 2023]. Global Cancer

Observatory. Globocan. Disponible en: https://gco.iarc.fr/

Wolff AC, Hammond MEH, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth

factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice

guideline update. J Clin Oncol. 2013;31(31):3997-4013. doi: 10.1200/JCO.2013.50.9984.

Ross JS, Fletcher JA. The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Semin Cancer Biol. 1999;9(2):125-38. doi: 10.1006/scbi.1998.0083. PMID: 10202134.

Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Redmond C, et al. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol. 1990;8(1):103-12. doi: 10.1200/JCO.1990.8.1.103.

Kallioniemi OP, Holli K, Visakorpi T, Koivula T, Helin HH, Isola JJ. Association of c-erbB-2 protein over-expression with high rate of cell

proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer. 1991;49(5):650-5. doi: 10.1002/ijc.2910490504. PMID: 1682277.

Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17(9):2639-48. doi: 10.1200/JCO.1999.17.9.2639.

Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-92. doi: 10.1056/NEJM200103153441101.

Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, et al. Randomized phase II trial of the efficacy and safety

of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer

administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005;23(19):4265-74. doi: 10.1200/JCO.2005.04.173.

Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable

HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-84. doi: 10.1056/NEJMoa052122.

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy

in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659-72. doi: 10.1056/NEJMoa052306.

Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer.

N Engl J Med. 2012;367(19):1783-91. doi: 10.1056/NEJMoa1209124.

von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617-628. doi: 10.1056/NEJMoa1814017.

Roche_Pharma_AG (2018) Perjeta® summary of product characteristics [Internet]. [citado el 1 de abril de 2019]. Disponible en:

https://www.ema.europa.eu/en/documents/product-information/perjeta-epar-product-information_en.pdf

Genentech_Inc. (2012) PERJETA prescribing information [Internet]. [citado el 1 de abril de 2019]. Disponible en: https ://www.acces sdata .fda.gov/drugs atfda docs/label /2012/12540 9lbl.pdf.

Novartis_Europharm_Ltd (2019) Tyverb summary of product characteristics [Internet]. [citado el 1 de abril de 2019]. Disponible en:

https ://www.ema.europ a.eu/en/docum ents/product-infor matio n/tyver b-epar-produ ct-infor matio n_en.pdf.

GlaxoSmithKline (2007) TYKERB prescribing information [Internet]. [citado el 1 de abril de 2019]. Disponible en: https://www.accesdata.fda.gov/drugs atfda docs/label /2010/022059s007 lbl.pdf.

Puma_Biotechnology_Inc. (2017) NERLYNX prescribing information [Internet]. [citado el 1 de abril de 2019]. Disponible en: https://www.acces sdata .fda.gov/drugs atfda docs/label2017/20805 1s000 lbl.pdf.

Puma_Biotechnology_Inc. (2018) Nerlynx® summary of product characteristics [Internet]. [citado el 1 de abril de 2019]. Disponible

en: https://www.ema.europ a.eu/en/docum ents/product-infor mation/nerly nx-epar-produ ct-infor matio n_en.pdf.

Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive

Metastatic Breast Cancer. N Engl J Med. 2020;382(7):597-609. doi: 10.1056/NEJMoa1914609.

Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022;386(12):1143-1154. doi: 10.1056/NEJMoa2115022.

Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, et al. CEREBEL (EGF111438): A Phase III, Randomized,

Open-Label Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth

Factor Receptor 2-Positive Metastatic Breast Cancer. J Clin Oncol. 2015;33(14):1564-73. doi: 10.1200/JCO.2014.57.1794.

Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, et al. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007;110(5):965-72. doi: 10.1002/cncr.22885.

Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, et al. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015;16(7):816-29. doi: 10.1016/S1470-2045(15)00051-0.

Paracha N, Reyes A, Diéras V, Krop I, Pivot X, Urruticoechea A. Evaluating the clinical effectiveness and safety of various HER2-targeted regimens after prior taxane/trastuzumab in patients with previously treated, unresectable, or metastatic HER2-positive breast cancer: a systematic review and network meta-analysis. Breast Cancer Res Treat. 2020;180(3):597-609. doi: 10.1007/s10549-020-05577-7.

Chen F, Chen N, Lv Z, Li L, Cui J. Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis. J Cancer. 2021;12(6):1687-1697. doi: 10.7150/jca.51845.

Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane Handbook for Systematic Reviews of Interventions.

Wiley-Interscience; Wiley-Blackwell; 2019. 728 p.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71.

Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162(11):777-84. doi: 10.7326/M14-2385.

Babineau J. Product Review: Covidence (Systematic Review Software). J Can Health Libr Assoc. 2014 Aug 1;35(2):68–71.

Covidence systematic review software. Veritas Health Innovation [Internet]. [citado el 1 de abril de 2019]. Disponible en: www.covidence.org

Higgins JPT, Savović J, Page MJ, Elbers RG, Sterne JAC. Assessing risk of bias in a randomized trial [Internet]. Cochrane Handbook for

Systematic Reviews of Interventions. Wiley; 2019. p. 205–28. [citado el 1 de abril de 2019]. Disponible en: https://onlinelibrary.wiley.com/

doi: 10.1002/9781119536604.ch8

Higgins JPT, Jackson D, Barrett JK, Lu G, Ades AE, White IR. Consistency and inconsistency in network meta-analysis: concepts and

models for multi-arm studies. Res Synth Methods. 2012;3(2):98-110. doi: 10.1002/jrsm.1044.

Puhan MA, Schünemann HJ, Murad MH, Li T, Brignardello-Petersen R, Singh JA, et al. A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ. 2014;349:g5630. doi: 10.1136/bmj.g5630.

Brignardello-Petersen R, Murad MH, Walter SD, McLeod S, Carrasco-Labra A, Rochwerg B, et al. GRADE approach to rate the certainty

from a network meta-analysis: addressing incoherence. J Clin Epidemiol. 2019;108:77-85. doi: 10.1016/j.jclinepi.2018.11.025.

Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of

HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol.

;22(3):351-360. doi: 10.1016/S1470-2045(20)30702-6.

Jiang Z, Yan M, Hu X, Zhang Q, Ouyang Q, Feng J, et al. Pyrotinib combined with capecitabine in women with HER2+ metastatic breast

cancer previously treated with trastuzumab and taxanes: A randomized phase III study. J Clin Orthod. 2019 May 20;37(15_suppl):1001–1001. doi: 10.1200/JCO.2019.37.15_suppl.1001.

Sim SH, Park IH, Jung KH, Kim SB, Ahn JH, Lee KH, et al. Abstract P6-17-23: Randomized phase II study of lapatinib plus vinorelbine

versus vinorelbine in patients with HER2 positive metastatic breast cancer progressed after lapatinib and trastuzumab treatment. Cancer Res. 2019 Feb 15;79(4_Supplement):P6–17 – 23–P6 – 17–23.

Ma F, Ouyang Q, Li W, Jiang Z, Tong Z, Liu Y, et al. Pyrotinib or Lapatinib Combined With Capecitabine in HER2–Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/ or Trastuzumab: A Randomized, Phase II Study. JCO. 2019;37:2610-2619. doi: doi:

1200/JCO.19.00108.

Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Lang I, Tomasello G, et al. Randomized Phase III Trial of Trastuzumab Plus Capecitabine With or Without Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Who Experienced Disease Progression During or After Trastuzumab-Based Therapy. J Clin Oncol. 2017;35(26):3030-3038. doi: 10.1200/JCO.2016.70.6267.

Urruticoechea A, Rizwanullah M, Im SA, Sánchez Ruiz AC, Lang I, Tomasello G, et al. Final overall survival (OS) analysis of PHEREXA:

A randomized phase III trial of trastuzumab (H) + capecitabine (X) ± pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) who experienced disease progression during or after H-based therapy. J Clin Orthod. 2018 May 20;36(15_suppl):1013–1013. doi:10.1200/JCO.2018.36.15_suppl.1013.

Bischoff J, Barinoff J, Mundhenke C, Bauerschlag DO, Costa SD, Herr D, et al. A randomized phase II study to determine the efficacy

and tolerability of two doses of eribulin plus lapatinib in trastuzumab-pretreated patients with HER-2-positive metastatic breast cancer

(E-VITA). Anticancer Drugs. 2019;30(4):394-401. doi: 10.1097/CAD.0000000000000722.

André F, O’Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, et al. Everolimus for women with trastuzumab-resistant, HER2-positive,

advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15(6):580-91.

doi: 10.1016/S1470-2045(14)70138-X.

Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, et al. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28(7):1124-30. doi:

1200/JCO.2008.21.4437.

Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, et al. 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.

;39(1):79-89. doi: 10.1200/JCO.20.01894.

Bian L, Xu BH, Di LJ, Wang T, Wang XJ, Jiao SC, et al. [Phase randomized controlled, multicenter, prospective study of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer: the HOPES Study]. Zhonghua Yi Xue Za Zhi. 2020;100(30):2351-2357. doi: 10.3760/cma.j.cn112137-20200116-00105.

Cortés J, Diéras V, Lorenzen S, Montemurro F, Riera-Knorrenschild J, Thuss-Patience P, et al. Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Phase 1 and Randomized Phase 2 Trial. JAMA Oncol. 2020;6(8):1203-1209. doi: 10.1001/jamaoncol.2020.1796.

Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, et al. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016;17(3):357-366. doi: 10.1016/S1470-2045(15)00540-9.

Takano T, Tsurutani J, Takahashi M, Yamanaka T, Sakai K, Ito Y, et al. A randomized phase II trial of trastuzumab plus capecitabine

versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and

taxanes: WJOG6110B/ELTOP. Breast. 2018;40:67-75. doi: 10.1016/j.breast.2018.04.010.

Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with

hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial. Lancet Oncol.

;21(6):763-775. doi: 10.1016/S1470-2045(20)30112-1.

Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732-742. doi: 10.1016/S1470-2045(17)30312-1.

Haddad TC, He J, O’Sullivan CC, Chen B, Northfelt D, Dueck AC, et al. Randomized Phase II Trial of Capecitabine and Lapatinib with or

without IMC-A12 (Cituxumumab) in Patients with HER2-Positive Advanced Breast Cancer Previously Treated with Trastuzumab and

Chemotherapy: NCCTG N0733 (Alliance). Breast Cancer Res Treat. 2021;188(2):477-487. doi: 10.1007/s10549-021-06221-8.

Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced

breast cancer: a multicentre study of Anatolian Society of Medical Oncology (ASMO). J Chemother. 2014;26(5):300-5. doi:

1179/1973947813Y.0000000147.

Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112(3):533-43. doi: 10.1007/s10549-007-9885-0.

von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, et al. Trastuzumab beyond progression in human epidermal

growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study. J Clin Oncol. 2009;27(12):1999-2006. doi: 10.1200/JCO.2008.19.6618.

Emens LA, Esteva FJ, Beresford M, Saura C, De Laurentiis M, Kim SB, et al. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol. 2020 Oct;21(10):1283-1295. doi: 10.1016/S1470-2045(20)30465-4.

Martin M, Bonneterre J, Geyer CE Jr, Ito Y, Ro J, Lang I, et al. A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer. Eur J Cancer. 2013;49(18):3763-72. doi: 10.1016/j.

ejca.2013.07.142.

Harbeck N, Im SA, Barrios CH, Bonnefoi HR, Gralow J, Toi M, et al. Primary analysis of KAITLIN: A phase III study of trastuzumab

emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk

HER2-positive early breast cancer (EBC). J Clin Orthod. 2020;38(15_suppl):500–500. doi:10.1200/JCO.2020.38.15_suppl.500.

Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724-34. doi: 10.1056/NEJMoa1413513.

Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, et al. Overall survival benefit with lapatinib in combination

with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the

EGF104900 Study. J Clin Oncol. 2012;30(21):2585-92. doi: 10.1200/JCO.2011.35.6725.

Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022;386(12):1143-1154. doi: 10.1056/NEJMoa2115022.

Published

2024-05-08

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1.
Ciapponi A, Bardach A, Colaci C, Rodríguez Cairoli F, Argento F, Korbenfeld E, et al. Trastuzumab-emtansine versus other anti-HER2 regimens in early or unresectable or metastatic HER2 positive breast cancer: systematic review and network meta-analysis. Rev Peru Med Exp Salud Publica [Internet]. 2024 May 8 [cited 2024 Dec. 23];41(1):7-18. Available from: https://rpmesp.ins.gob.pe/index.php/rpmesp/article/view/13351

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