Abstract LB-225: Phase 2 Trial of nab-paclitaxel plus carboplatin for advanced NSCLC in patients at risk of bleeding from VEGF directed therapies
Authors: Bertino Erin M. , Villalona-Calero Miguel A. , Nana-Sinkam Patrick , Cantrel Sarah , Rahmani Meliha , Symmes Carrie , Phillips Gary S. , Otterson Gregory A. 
Published: August 2012

Abstract
Background: The addition of bevacizumab (Bev) to platinum based chemotherapy results in higher response rate (RR), progression-free survival (PFS), and overall survival (OS) in advanced non-small cell lung cancer (NSCLC). However, Bev is not indicated in patients (pts) with squamous histology or with hemoptysis due to bleeding risk. Nab-paclitaxel is a novel formulation of paclitaxel with higher dose tolerance and potentially improved efficacy. A previous study of nab-paclitaxel/Carboplatin (using an alternative schedule) showed a higher response rate in patients with squamous histology (Socinski, et al, ASCO 2010, LBA7511). We hypothesized that in pts with NSCLC ineligible for Bev therapy the combination of nab-paclitaxel and carboplatin (Cb) would be superior to alternative doublets. Methods: We conducted a single-arm, single-institution phase 2 trial (NCT00729612) to evaluate RR (primary endpoint), safety/toxicity, and survival (OS, PFS - secondary endpoints) in patients treated with nab-paclitaxel and carboplatin (Cb). Eligible pts included: squamous histology, history of hemoptysis, requirement for anticoagulation. Correlative studies included blood microRNA profiles pre-treatment. Treatment was administered every 21 days, initially at 300 mg/m2/AUC=6, but then adjusted to 260 mg/m2/AUC6 due to excess neuropathy. Results: 63 pts (21 female, 42 male) with median age 63 yrs (range 36-82) were enrolled. Pts had an average 50 pk-yrs tobacco use. The most common histology was squamous cell carcinoma (48 pts/76%), followed by adenocarcinoma (9 pts/14%), NSCLC NOS (4 pts/6%) and adenosquamous (2 pts/3%). In non-squamous pts, eligibility criteria included hemoptysis (11 pts), thrombosis (2 pts), and therapeutic anticoagulation (1 pt). Grade 3-4 toxicities seen in more than 10% of pts included hematologic toxicity (36 pts/57%), febrile neutropenia (9/14%), infection (15/24%), sensory neuropathy (17/27%), dyspnea (10/16%) and dehydration (8/13%). Four deaths_including 1 sudden death and 1 death due to respiratory failure_were reported on study as grade 5 toxicity. ORR was 41% (22 PR/0 CR) in the 53 pts evaluable to date with 39% (21 pts) stable disease and 19% (10 pts) progressive disease. PFS/OS data is not yet available. Conclusions: The combination of Cb and nab-paclitaxel demonstrates promising efficacy with tolerable toxicity in NSCLC pts ineligible for Bev therapy. Further study in the squamous cell population is warranted. Correlative studies of microRNA profiles and survival data (OS and PFS) is maturing and will be available in the near future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-225. doi:1538-7445.AM2012-LB-225