Oct 4, 2018 09:12PM Lumpie wrote:Paclitaxel With Inhibitor of Apoptosis Antagonist LCL161 for Localized Triple-Negative Breast Cancer
- Journal of Clinical Oncology
- Women with localized triple-negative breast cancer (T2/N0–2/M0) were prospectively stratified by a tumor necrosis factor-α (TNFα)–based gene expression signature (GS) and randomly assigned to receive oral LCL161 (inhibitor of apoptosis antagonist) and intravenous paclitaxel or paclitaxel alone for 12 weeks, followed by surgery. Those in the GS-positive group experienced improved pathologic complete response with combination therapy relative to paclitaxel alone (38.2% vs 17.2%). For patients in the GS-negative group, pathologic complete response was inferior with combination therapy relative to paclitaxel alone (5.6% vs 16.4%). Patients receiving combination therapy experienced higher rates of adverse events such as neutropenia (24.5%) and diarrhea (5.7%) and were more likely to discontinue treatment due to adverse events than were patients receiving paclitaxel alone (18.1% vs 4.9%).
- The study authors conclude that the biomarker-driven targeted therapy approach shows promise in terms of efficacy; however, elevate rates of adverse events must be taken into consideration.
- This neoadjuvant trial provides evidence supporting a biomarker-driven targeted therapy approach for selected patients with GS-positive TNBC and demonstrates the utility of a neoadjuvant trial for biomarker validation and drug development, but also highlights toxicity risk. Future neoadjuvant clinical trials should carefully weigh these considerations for targeted therapy development in biomarker-defined TNBC.
DOI: 10.1200/JCO.2017.74.8392 Journal of Clinical Oncology