The efficacy of HER2-targeted agents in metastatic breast cancer: a meta-analysis.
BACKGROUND
The addition of HER2-targeted agents to standard treatment has been shown to improve outcomes for HER2 positive metastatic breast cancer patients. We undertook a meta-analysis to evaluate the efficacy of HER2-targeted therapy in addition to standard treatment in metastatic breast cancer patients.


METHODS
Eligible trials were randomised controlled trials (RCTs) comparing the addition of HER2 therapy to standard treatment (hormone or chemotherapy) reporting overall survival (OS), time to progression (TTP), progression-free survival (PFS) and/or response rates.


RESULTS
Eight trials comprising 1848 patients were eligible for inclusion. HER2-targeted agents were trastuzumab and lapatinib and therapeutic partners were taxanes (4 RCTs), anthracyclines (1), capecitabine (2), anastrozole (1) and letrozole (1). The addition of HER2-targeted agents improved OS [hazard ratios (HR) 0.78; 95% confidence interval (CI) 0.67-0.91], TTP (HR 0.56; 95% CI 0.48-0.64), PFS (HR 0.63; 95% CI 0.53-0.74) and overall response rate (relative risk 1.67; 95% CI 1.46-1.90).


CONCLUSIONS
Our meta-analysis confirms the benefit of adding HER2-targeted therapy to standard treatment in HER2 positive metastatic breast cancer. Compared with OS, TTP, PFS and ORR overestimate treatment benefit. Trials in our meta-analysis differed in terms of partner drug or HER2 agents, yet delivered comparable outcomes.
Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
C A
CA
Harris
Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
R L
RL
Ward
Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
T A
TA
Dobbins
Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
A K
AK
Drew
Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. Electronic address: sallie.pearson@unsw.edu.au.
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Pearson
D000077384:Anastrozole; D018943:Anthracyclines / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000077341:Lapatinib; D000077289:Letrozole; D009362:Neoplasm Metastasis; D009570:Nitriles / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D043823:Taxoids / Q000627:therapeutic use; D000068878:Trastuzumab; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use
D000077384:Anastrozole; D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D000077289:Letrozole; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; D014230:Triazoles; C508053:ERBB2 protein, human