Current treatment landscape in triple negative breast cancer: A systematic literature review

Abstract

Background: Triple negative breast cancer (TNBC) accounts for 15-20% of breast cancer diagnoses. As novel targets and therapies for TNBC emerge, a comprehensive overview of the current landscape of evidence on the approved or developing treatment options was needed Methods: We followed Cochrane guidelines for systematic literature reviews (SLR). Population of interest was adult female patients with TNBC receiving any pharmacological treatment. Studies of interest were randomized controlled trials (RCTs) or comparative non-randomized clinical trials (non-RCTs). Outcomes included survival, disease and pathological response, and adverse events. A search from January 2003 to July 2018 was performed on MEDLINE , Embase, the Cochrane Central Database of Controlled Trials, and the US and European clinical trials registries. Conference proceedings from ASCO, ESMO, and SABCS covering the period from 2016 to end of 2018 were also reviewed. Result(s): Eighty-nine publications corresponding to 77 unique trials met the eligibility criteria for this review. The 72 RCTs and 5 comparative non-RCTs were predominantly open-label phase 2 or 3 trials. Immune checkpoint inhibitors, including nivolumab, atezolizumab, durvalumab, and pembrolizumab, were evaluated in 5 trials. Targeted therapies, primarily VEGF inhibitors (n=12) and PARP inhibitors (n=7), were evaluated in 40 trials. Thirty-two trials evaluated chemotherapy alone, with the majority assessing chemotherapy combinations of 2 or more subclasses. Thirty-five trials reported treatments on metastatic or advanced TNBC, 31 on neoadjuvant and 11 on adjuvant therapies. Overall survival (n=32) and progression-free survival (n=30) were the most commonly reported efficacy outcomes. Safety outcomes were reported in 39 trials. Conclusion(s): Targeted therapies, followed by chemotherapy in forms of combinations of 2 or more subclasses, composed most trials in TNBC, with immunotherapy being rarely used thus far. The trials were mainly conducted in metastatic or advanced setting, followed by neoadjuvant and adjuvant settings. Comparison across different TNBC treatment options warrants further investigation as the growing evidence base evolves.