title: Increased life expectancy as a result of non-hormonal targeted therapies for HER2 or hormone receptor positive metastatic breast cancer: A systematic review and meta-analysis.
abstract: This article aimed to assess the clinical effectiveness of non-hormonal targeted therapies (TTs) in terms of increase of median progression-free survival (PFS) and overall survival (OS) in receptor-positive metastatic breast cancer (MBC) patients by performing a systematic review and meta-analysis. We systematically searched relevant randomized controlled trials and extracted data about number of patients on targeted and comparator therapy, receptor status, line of treatment, median PFS and OS, p values, hazard ratios (HRs) and 95% confidence intervals (CI). Inverse variance was used to estimate pooled HRs, chi-square test for heterogeneity and Jadad scale for quality were applied. Thirty-eight studies (n=17,192 patients) were eligible for inclusion. TTs added 3.3months to the median PFS [0.7-9.6; HRs 0.74, 95% CI 0.71-0.77] of receptor-positive MBC patients and prolonged their median OS with 3.5months [0-4.7; HRs 0.90, 95% CI 0.82-0.98]. The highest increase in median PFS of 3.6months was found in HER2-/hormone receptor(HR)+ patients, while the highest increase in median OS of 7.2months was observed in HER2+/HRmixed status patients. First-line TTs were most effective in increasing the median PFS in the HR+/HER2- group with 2.0months, and in the HER2+/HRmixed group by adding 4.7months to the median OS. Second-line TTs were most effective for HER2-/HR+ patients by adding 2.6months to their PFS, and for HER2+/HRmixed patients by adding 3.1months to their median OS. Albeit small, the gain in months of median PFS and median OS was significant. Importantly, the results reported show large variation, and thus routinely applying a personalized approach seems warranted.
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700RB Groningen, The Netherlands; Department of Primary Care and Public Health Sciences, Division of Health and Social Care Research, King's College London, Guy's, AH 3.2, SE1 1UL London, United Kingdom. Electronic address: r.koleva-kolarova@umcg.nl.
authors.forename: Rositsa G
authors.initials: RG
authors.lastname: Koleva-Kolarova
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700RB Groningen, The Netherlands. Electronic address: monikapury@gmail.com.
authors.forename: Monika P
authors.initials: MP
authors.lastname: Oktora
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700RB Groningen, The Netherlands. Electronic address: annelies.l.robijn@gmail.com.
authors.forename: Annelies L
authors.initials: AL
authors.lastname: Robijn
authors.affiliation: Department of Radiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700RB Groningen, The Netherlands. Electronic address: m.j.w.greuter@umcg.nl.
authors.forename: Marcel J W
authors.initials: MJW
authors.lastname: Greuter
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700RB Groningen, The Netherlands. Electronic address: a.k.l.reyners@umcg.nl.
authors.forename: Anna K L
authors.initials: AKL
authors.lastname: Reyners
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700RB Groningen, The Netherlands. Electronic address: e.buskens@umcg.nl.
authors.forename: Erik
authors.initials: E
authors.lastname: Buskens
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700RB Groningen, The Netherlands. Electronic address: g.h.de.bock@umcg.nl.
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D000068338:Everolimus / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008017:Life Expectancy; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015996:Survival Rate; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D000068338:Everolimus; D000077341:Lapatinib; D010879:Piperazines; D011725:Pyridines; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C500026:palbociclib; C485206:pertuzumab
keywords: Breast neoplasm; Estrogen receptors; Human epidermal growth factor receptor 2; Molecular targeted therapy; Progesterone receptors; Survival analysis