The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer – a systematic review

Abstract

IntroductionThis study aimed at evaluating the overall survival (OS) gain associated with human epidermal growth factor receptor 2 (HER2)-directed therapies in patients with metastatic breast cancer (mBC).MethodsA bibliographic search was conducted in PubMed and Cochrane databases. Only phase III randomized controlled trials (RCTs) including HER2-positive (HER2+) mBC patients were included in this review. OS was defined as time from randomization until the occurrence of death from any cause. Studies have been grouped according to the line of treatment, i.e., first-line or second-line or beyond.ResultsNineteen RCTs were eligible for inclusion, of which 12 assessed therapies targeting HER2+ mBC in the first-line setting. OS improved from 20.3 months in the first RCT (standard chemotherapy; Slamon et al. (N Engl J Med 344:783–92, 2001)) evaluating HER2-targeting therapies to 48 months in the study of Swain et al. (Lancet Oncol 14:461–71, 2013), with triple combination of pertuzumab, trastuzumab and docetaxel. Seven RCTs evaluated the OS of HER2-targeting therapies in the second-line setting and beyond. The OS in second-line setting improved from 15.3 months (capecitabine; Cameron et al. (Breast Cancer Res Treat 112:533–43, 2008)) to 30.7 months (trastuzumab emtansine; Verma et al. (N Engl J Med 367:1783–91, 2012)). In the third-line setting, the association of lapatinib and trastuzumab has demonstrated to improve OS to 4.5 months compared with lapatinib alone (14 months vs. 9.5 months; Blackwell et al. (J Clin Oncol 30:2585–92, 2012)).ConclusionsHER2-directed therapies had an undeniable beneficial impact on the OS of patients with HER2+ mBC. The triple combination of docetaxel, pertuzumab and trastuzumab is associated with a survival extent of more than 4.5 years, compared with a life expectancy of 1.5 years achieved 14 years ago.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0648-2) contains supplementary material, which is available to authorized users.

An Anti-GDNF Family Receptor Alpha 1 (GFRA1) Antibody–Drug Conjugate for the Treatment of Hormone Receptor–Positive Breast Cancer

“…One to 4 days before inoculation of the MCF7 or MCF7-neo/HER2 cells, mice were implanted subcutaneously with a 0.36 mg, 60-day sustained release 17b estradiol pellet (Innovative Research of America). Once tumors reached a mean volume of 195-350 mm 3 , mice with similarly sized tumors were randomized into treatment groups (n ¼ 8-10/group) and an intravenous dose of vehicle (20 mmol/L Histidine-Acetate Buffer), mu control ADC (mu-gp120-ADC), mu-anti-GFRA1 ADCs, hu-control ADC (hu-gD-ADC), or hu-anti-GFRA1 ADCs were administered. Length (l) and width (w) of each tumor were measured using digital calipers (Fred V. Fowler Company, Inc.) and tumor volumes were calculated (V ¼ lw 2 Â 0.5).…”

“…In addition to hormone therapy, there are several targeted therapeutic treatment options that can either inhibit the hormone receptor signaling or lower hormone receptors levels. The HER2-enriched subgroup representing 4% of all breast cancers, is the most aggressive cancer, but with several HER2-targeted treatment options (3). Luminal B constitutes 10% of cases and can either be treated using luminal A cancer treatment options or available HER2-targeted therapies.…”

Combination therapy approaches to target insulin-like growth factor receptor signaling in breast cancer

“…doxorubicin, 5-fluorouracil and docetaxel), which is not reflective of the intrinsic molecular profiles of these cancers (Pal et al 2011). For HER2-amplified breast cancers, a number of HER2-directed therapies, including the monoclonal antibodies (mAbs) trastuzumab and pertuzumab, which inhibit HER2/HER3 dimerization and activity, the dual tyrosine kinase inhibitor -lapatinib -which inhibits HER2 and EGFR activity and T-DMI (an antibody drug-conjugate of the mAb, trastuzumab and the chemotherapy drug DMI (emtansine)) (Verma et al 2012, Mendes et al 2015, have been developed and are clinically used. Currently, there are no targeted therapies for TNBC, which are widely used although many drugs designed to inhibit the emerging pathways are in clinical development (Kalimutho et al 2015).…”

131I-labeled Anti-HER2 Camelid sdAb as a Theranostic Tool in Cancer Treatment

“…Treatment goals are mainly focused on prolonging overall survival (OS) and progression free survival (PFS). Therapies targeting HER2 can significantly impact the outcome of HER2 + metastatic BC (4): since the introduction of anti-HER2 drugs to the standard of care, OS has increased significantly. However, emerging resistance to trastuzumab and the kinase-inhibitor lapatinib are frequently observed.…”