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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.

Original publication




Journal article


Cancer Treat Rev

Publication Date





16 - 25


Breast neoplasm, Estrogen receptors, Human epidermal growth factor receptor 2, Molecular targeted therapy, Progesterone receptors, Survival analysis, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Bevacizumab, Breast Neoplasms, Disease-Free Survival, Everolimus, Female, Humans, Lapatinib, Life Expectancy, Molecular Targeted Therapy, Neoplasm Metastasis, Piperazines, Pyridines, Quinazolines, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Survival Rate, Trastuzumab