Abstract P4-22-11: 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
Authors: 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 
Published: March 2017

Abstract
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.