Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr;180(3):597-609.
doi: 10.1007/s10549-020-05577-7. Epub 2020 Feb 25.

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

Noman Paracha  1 , Adriana Reyes  2 , Véronique Diéras  3 , Ian Krop  4 , Xavier Pivot  5 , Ander Urruticoechea  6
Affiliations

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

Noman Paracha et al. Breast Cancer Res Treat. 2020 Apr.

Abstract

Purpose: In the absence of head-to-head trial data, network meta-analysis (NMA) was used to compare trastuzumab emtansine (T-DM1) with other approved treatments for previously treated patients with unresectable or metastatic HER2-positive breast cancer (BC).

Methods: Systematic reviews were conducted of published controlled trials of treatments for unresectable or metastatic HER2-positive BC with early relapse (≤ 6 months) following adjuvant therapy or progression after trastuzumab (Tras) + taxane published from January 1998 to January 2018. Random-effects NMA was conducted for overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety endpoints.

Results: The NMA included regimens from seven randomized controlled trials: T-DM1 and combinations of Tras, capecitabine (Cap), lapatinib (Lap), neratinib, or pertuzumab (Per; unapproved). OS results favored T-DM1 over approved comparators: hazard ratio (HR) (95% credible interval [95% CrI]) vs Cap 0.68 (0.39, 1.10), LapCap 0.76 (0.51, 1.07), TrasCap 0.78 (0.44, 1.19). PFS trends favored T-DM1 over all other treatments: HR (95% CrI) vs Cap 0.38 (0.19, 0.74), LapCap 0.65 (0.40, 1.10), TrasCap 0.62 (0.34, 1.18); ORR with T-DM1 was more favorable than with all approved treatments. In surface under cumulative ranking curve (SUCRA) analysis T-DM1 ranked highest for all efficacy outcomes. Discontinuation due to adverse events was less likely with T-DM1 than with all comparators except neratinib. In general, gastrointestinal side effects were less likely and elevated liver transaminases and thrombocytopenia more likely with T-DM1 than with comparators.

Conclusions: The efficacy and tolerability profiles of T-DM1 are generally favorable compared with other treatments for unresectable or metastatic HER2-positive BC.

Keywords: Capecitabine; Lapatinib; Locally advanced; Neratinib; Pertuzumab; Trastuzumab emtansine.

PubMed Disclaimer

Conflict of interest statement

NP is an employee of F. Hoffmann-La Roche AG and owns F. Hoffmann-La Roche AG stock. AR is an employee of F. Hoffmann-La Roche AG. VD Consultant/Advisory role: AbbVie, Astellas, AstraZeneca, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Nektar, Novartis, Odonate, Pfizer, Roche/Genentech, Seattle Genetics, Tesaro. IK Consultant/Advisory role: Bristol-Myers Squibb, Context Therapeutics, Daiichi Sankyo, MacroGenics, Merck, Novartis, Roche/Genentech, Seattle Genetics, Taiho Oncology. XP has nothing to declare. AU has received travel support from Roche.

Figures

Fig. 1
Fig. 1
PRISMA diagram of included and excluded studies (aRespectively, the record numbers shown are those from the initial SR covering 1 January 1998 to 2 July 2013, from the first update of the SR, covering 1 October 2012 to 30 June 2016, and from the second update of the SR, covering 1 January 2016 to 3 January 2018. bFor each clinical study only the primary references, and not conference abstracts, are cited in the text). A PRISMA checklist is provided in Online Resource 11. PRISMA Preferred Reporting Items for Systematic Reviews and Meta-analyses, SR systematic review
Fig. 2
Fig. 2
Treatment network plots for a OS, adjusted OS, PFS, and b ORR. Cap capecitabine, Lap lapatinib, ORR overall response rate, OS overall survival, Per pertuzumab, PFS progression-free survival, T-DM1 trastuzumab emtansine, Tras trastuzumab
Fig. 3
Fig. 3
Comparative effectiveness of T-DM1 on OS, adjusted OS, and PFS. Comparators are shown in order of SUCRA ranking, with treatments ranking highest after T-DM1 at the top of the plot. Cap capecitabine, CrI credible interval, HR hazard ratio, Lap lapatinib, OS overall survival, Per pertuzumab, PFS progression-free survival, SUCRA surface under cumulative ranking curve, T-DM1 trastuzumab emtansine, Tras trastuzumab
Fig. 4
Fig. 4
Comparative effectiveness of T-DM1 on ORR. Comparators are shown in order of SUCRA ranking, with treatments ranking highest after T-DM1 at the top of the plot. Cap capecitabine, CrI credible interval, Lap lapatinib, OR odds ratio, ORR overall response rate, Per pertuzumab, SUCRA surface under cumulative ranking curve, T-DM1 trastuzumab emtansine, Tras trastuzumab
Fig. 5
Fig. 5
Comparative effectiveness of T-DM1 on AEs: a SAEs and AEs leading to discontinuation; b AEs by preferred term. Comparators are shown in order of SUCRA ranking, with treatments ranking highest at the top of the plot. T-DM1 ranks: discontinuation (grade 3+), SAEs, diarrhea, nausea, fatigue, first; vomiting, second; neutropenia, third; increased ALT, fourth; increased AST, fifth. AE adverse event, ALT alanine aminotransferase, AST aspartate aminotransferase, Cap capecitabine, CrI credible interval, Lap lapatinib, OR odds ratio, Per pertuzumab, SAE serious adverse event, SUCRA surface under cumulative ranking curve, T-DM1 trastuzumab emtansine, Tras trastuzumab
See this image and copyright information in PMC

References

    1. Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26(45):6469–6487. doi: 10.1038/sj.onc.1210477. - DOI - PMC - PubMed
    1. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF, American Society of Clinical Oncology, College of American Physicians (2013) 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 31(31):3997–4013. 10.1200/JCO.2013.50.9984 - PubMed
    1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–182. doi: 10.1126/science.3798106. - DOI - PubMed
    1. Roche_Pharma_AG (2018) Herceptin® summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/herceptin-epa.... Accessed 01 Apr 2019
    1. Genentech_Inc (2010) HERCEPTIN prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103792s5250lbl.... Accessed 01 Apr 2019

Publication types

MeSH terms