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.

Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study

“…Over the past 2 decades, the availability of human epidermal growth factor receptor 2 (HER2)-targeted therapies has significantly improved clinical outcomes for patients with HER2-positive breast cancer, 1 , 2 defined as tumors with high levels of HER2 protein expression as assessed by immunohistochemistry (IHC) and/or are HER2 amplified as assessed by in situ hybridization (ISH). 3 , 4 However, between 40% and 50% of patients with breast cancer have tumors with low HER2 expression (defined as IHC 1+ or IHC 2+ and ISH−), which is a heterogeneous population including both luminal-type hormone receptor (HR)-positive and triple-negative breast cancers.…”

Molecular imaging with positron emission tomography and computed tomography (PET/CT) for selecting first-line targeted treatment in metastatic breast cancer: a cost-effectiveness study

“…The distribution of the locations of MBC was obtained from a cohort of patients diagnosed with primary disease and subsequently developed MBC within a 5-year follow-up [ 25 ]. The overall survival estimates were based on meta-analyses and RCTs of receptor positive MBC patients treated with targeted, hormonal and chemo- therapies [ 5 , 26 – 30 ]. The inconclusive rate of pathology and the rate of unobtainable pathology samples were based on previous publications [ 9 – 11 , 16 ].…”

“…Life years gained were modeled by assigning survival periods to the different health states. These survival periods were obtained from meta-analyses and RCTs which estimated overall survival of MBC patients treated with targeted, hormonal and chemo- therapies [ 5 , 26 – 30 ].…”

“…Patients with negative receptor status (HER2- and HR-negative) of the metastatic disease do not respond to targeted therapy in general, therefore, chemotherapy remains as a treatment option [ 3 , 4 ]. Targeted therapy for MBC can potentially prolong the survival of MBC patients [ 5 ], but can also be costly and may bring adverse effects. New targeted therapies regularly become available (e.g.…”

“…palbociclib, pertuzumab) and a prior selection of patients is crucial to optimize outcomes of targeted therapy at acceptable costs. Moreover, this may also improve progression-free and overall survival [ 5 ], and further minimize adverse effects and avoid unnecessary harms and associated costs for those who do not respond.…”