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

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...

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Bibliographic Details
Published in:Breast cancer research and treatment Vol. 180; no. 3; pp. 597 - 609
Main Authors: Paracha, Noman, Reyes, Adriana, Diéras, Véronique, Krop, Ian, Pivot, Xavier, Urruticoechea, Ander
Format: Journal Article
Language:English
Published: New York Springer US 01.04.2020
Springer
Springer Nature B.V
Subjects:
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Bridged-Ring Compounds - administration & dosage
Cancer research
Care and treatment
Clinical trials
ErbB-2 protein
Female
Humans
Immunotherapy
Inhibitor drugs
Medicine
Medicine & Public Health
Meta-analysis
Metastases
Metastasis
Molecular Targeted Therapy
Monoclonal antibodies
Oncology
Pertuzumab
Receptor, ErbB-2 - antagonists & inhibitors
Review
Survival
Targeted cancer therapy
Taxoids - administration & dosage
Thrombocytopenia
Trastuzumab
Trastuzumab - administration & dosage
Treatment Outcome
Trastuzumab emtansine
Lapatinib
Pertuzumab
Capecitabine
Neratinib
Locally advanced
ISSN:0167-6806, 1573-7217, 1573-7217
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Summary: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.
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ISSN:0167-6806
1573-7217
1573-7217
DOI:10.1007/s10549-020-05577-7