Abstract P6-07-01: A translational and five-year clinical update in patients treated with neoadjuvant chemotherapy randomized to bevacizumab or control in HER2 negative breast cancer
Authors: Gythfeldt HvdL , Engebråten O , Naume B , Wist E , Borgen E , Lien T , Lindgjærde OC , Garred O , Schlichting E , Silwal-Pandit L , Borresen-Dale AL 
Published: May 2019

Abstract
Background: Bevacizumab added to conventional neoadjuvant chemotherapy increase the proportion of patients achieving a pathological complete response (pCR). Identifying patients responding to antiangiogenic therapy have been challenging. The primary objective of this study was to determine the molecular characteristics and treatment induced changes of the primary tumors with reference to treatment response. Clinical outcome measurements according to treatment were exploratory endpoints. Recent updated clinical results, in addition to extended molecular analyses are presented.
Methods: A phase II randomized clinical trial of HER2 negative primary tumors of ≥25 mm (n=132) was conducted, treated with neoadjuvant chemotherapy (4xFEC100 followed by taxane-based therapy) with or without the addition of bevacizumab. Biopsies were obtained at the time of diagnosis, after 12 weeks of treatment, and after 25 weeks at surgery. The response was evaluated using the criteria for determining the residual cancer burden (RCB). We derived a mean immune score per patient by calculating the average score from the 770 genes in the nCounter PanCancer immune panel to detect an association between immune activity and response to antiangiogenic therapy. In addition, the median five-year follow-up for disease recurrence are reported.
Results: The addition of bevacizumab increased the RCB class 0 (pCR) rate in the study population from 12% to 17% and the rate of “good responders” (RCB class 0 and 1) from 24% to 33%, without reaching statistical significance. A pronounced effect of bevacizumab combination therapy was observed in the hormone receptor (HR) positive tumors, were the percentage of patients achieving RCB class 0 increased from 5% to 20% (Fisher's Exact test, p=0.02). More HR positive patients achieved a good response and fewer patients were poor responders (RCB class 3) in the combination treatment arm (Wilcoxon, p=0.035). Previously, our unsupervised analyses demonstrated an enrichment of immune related genes in pretreatment samples from patients responding to combination therapy. A significantly higher mean immune score (p&lt;0.001) was detected among the HR positive patients who received bevacizumab and achieved RCB class 0 after neoadjuvant treatment (n=11, 20%) . Five-year follow-up data revealed a total of 21 events in the study population; 9 relapses in patients treated with combination therapy, and 12 relapses in patients treated with chemotherapy only. DFS was not statistically different between the treatment groups (log rank, p=0.4257). However, among the patients achieving a good response an improved DFS was observed for those treated with combination therapy (1/22 vs. 5/16, log rank, p=0.0254).
Conclusion: Among locally advanced HER2-negative HR positive breast cancer patients, the addition of bevacizumab to neoadjuvant chemotherapy increased the rate of good responders and improved the DFS among these patients. An increased primary tumor immune score may predict good response to neoadjuvant antiangiogenic therapy in HR positive disease. Further studies are needed to validate the use of such immune panels for selection of patients most likely to benefit from antiangiogenic therapy.
Citation Format: Gythfeldt HvdL, Engebråten O, Naume B, Wist E, Borgen E, Lien T, Lindgjærde OC, Garred O, Schlichting E, Silwal-Pandit L, Borresen-Dale AL. A translational and five-year clinical update in patients treated with neoadjuvant chemotherapy randomized to bevacizumab or control in HER2 negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-07-01.