#6006 Background: We are enrolling patients with locally-advanced (LABC) or inflammatory breast cancer on a phase II trial of neoadjuvant sunitinib and metronomic chemotherapy. The addition of sunitinib is hypothesized to increase rate of pathologic complete response (pCR) via its effect on tumor vasculature. Measurement of FDG PET and MRI parameters of metabolism and blood flow (BF) after a one week run-in of sunitinib alone provides an opportunity to evaluate in vivo pharmacodynamics of sunitinib which may be predictive of response and provide insight into mechanism of sunitinib activity. Materials and Methods: Patients with HER2 negative LABC participated in an imaging trial with pre-therapy [18F]-FDG PET and DCE-MRI (T0) followed by a one-week run-in of sunitinib 37.5 mg orally daily with a second PET and MRI on day 7 (T1). FDG metabolic rate (MRFDG), transport (FDG K1) and MR indices of tumor perfusion (peak enhancement (PE), signal enhancement ratio (SER), and washout volume(WV)) were assessed. Results: Metabolism and perfusion parameters are available for the first 3 patients treated on this trial. All patients presented with grade 3, HER2 negative LABC. DCI-MRI (left) and PET images (right) pre-therapy (T0, top) and after one week sunitinib (T1, bottom) are illustrated in Figure 1. DCE-MRI studies show gray-scale images with color-coded regional perfusion (SER) superimposed; red indicates high levels of perfusion and blue lower levels. Three different responses were observed and expressed as percent change T0 to T1: patient 1 had no significant change in metabolism (MRFDG) or perfusion (K1,SER, PE); patient 2 showed a decline in perfusion with decreases in K1 (-55%), SER (-19%), PE (-10%), and WV (-56%), but minimal change in MRFDG (+ 5.9%); while patient 3 had marked declines in perfusion K1 (-41%), SER (-25%), WV (-78%) and MRFDG (-59%). Discussion: These early data demonstrate the ability to measure changes in tumor metabolism and blood flow by PET and MRI and illustrate heterogeneity in tumor response to sunitinib. As patients complete neoadjuvant chemotherapy (NC), metabolism and perfusion parameters from mid-therapy (T2) and end-therapy (T3) imaging will be evaluated in the context of pCR versus other with the goal of exploiting functional imaging parameters to predict response to NC and elucidate mechanism of response to sunitinib and metronomic chemotherapy. Supported by grant from NCCN, SI11.
 
 Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6006.
Background: Chemotherapy remains the mainstay of therapy for patients with metastatic triple negative breast cancer (TNBC). We hypothesized that the addition of biologic agents targeting key pathways (bevacizumab targeting angiogenesis and erlotinib directed against EGFR) may prolong progression free survival (PFS) and offer a novel treatment strategy free from chemotherapy for patients with metastatic TNBC. Methods: Patients with TNBC receiving initial therapy for metastatic disease were eligible for this multicenter phase II trial (NCT00733408) conducted at an academic center and affiliated, community practice sites. Induction therapy included nab-paclitaxel 100 mg/m2 IV Qweek (wk) and Bevacizumab 10 mg/kg IV Q2wks x 24 weeks. Patients free of progression at 24 wks began maintenance therapy with bevacizumab 10 mg/kg IV Q2wks and erlotinib 150 mg po daily until progression with radiographic assessment every 8 wks. Primary objective was PFS with secondary objectives of response rate, overall survival (OS) and safety. All eligible patients were included in the analysis of PFS and OS. Response was evaluated among patients with measurable disease by RECIST 1.1 with central review. Patients with inadequate disease assessments were coded as non-responders. Kaplan-Meier method was used to estimate PFS and OS with patients censored at date of last tumor assessment (PFS) or date of last follow up (OS). Results: From April 2009 – December 2015, 58 patients (median age 54, range 33-83) were enrolled; 56 (97%) had measurable disease, and all had metastatic TNBC by local assessment. 33 (57%) patients completed induction; 22 (38%) came off study during induction; 3 (5%) continue on maintenance therapy. 4 patients discontinued therapy prior to first assessment. As of June 8, 2016, 53 patients (91%) have progressed. Median follow up for surviving patients is 14.5 months (range 4.1-65.4). Median PFS is 7.7 months (95% CI 5.7, 9.5). Of 56 patients with measurable disease, 38 (66%) had partial response (PR); 10 (17%) with stable disease for clinical benefit rate (CBR) of 86%. Median OS is 18.2 months (95% CI 16.3, 24.5). Most common grade 3-4 toxicities during induction were neutropenia [17 (29%), 1 grade 4], fatigue [13 (22%), all grade 3], leukopenia [7 (12%), all grade 3], and neuropathy [7 (12%), all grade 3]. Rash was most common ≥ grade 3 toxicity during maintenance [4 (7%), grade 3]. One patient experienced clinical CHF during maintenance month 16 requiring bevacizumab discontinuation. Conclusions: Nab-paclitaxel and bevacizumab followed by maintenance targeted therapy with bevacizumab and erlotinib was well tolerated. While the observed PFS did not meet pre-specified criteria of interest, the majority of patients experienced clinical benefit (86%) with 30 (57%) receiving maintenance targeted therapy. Correlative studies are ongoing. Supported by Genentech (OSI4266s), Celegene (AX-CL-BRST-PI-003828) and Janssen. Citation Format: Specht JM, Gadi VK, Gralow JR, Korde LA, Linden HM, Salazar LG, Rodler ET, Cundy A, Buening BJ, Baker KK, Redman MW, Kurland BF, Garrison MA, Smith JC, vanHaelst C, Anderson JE. Combined targeted therapies for advanced triple negative breast cancer: A phase II trial of nab-paclitaxel and bevacizumab followed by maintenance targeted therapy with bevacizumab and erlotinib [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-11.
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