title: Stromal Caveolin-1 Is Associated With Response and Survival in a Phase II Trial of nab-Paclitaxel With Carboplatin for Advanced NSCLC Patients.
abstract: In this phase II trial, carboplatin with nanoparticle albumin-bound (nab)-paclitaxel as first-line therapy for advanced non-small-cell lung cancer (NSCLC) was evaluated. Most patients had squamous cell histology. Tumor-associated stromal caveolin-1 (Cav-1) expression was correlated with improved response rate and survival in NSCLC patients who received nab-paclitaxel in this phase II trial. These results suggest Cav-1 might serve as a potential biomarker in this patient population.
  
  
  BACKGROUND
  The combination of bevacizumab with platinum-based chemotherapy results in greater response rate (RR) and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). Bevacizumab is contraindicated in patients with squamous histology or hemoptysis. Nanoparticle albumin-bound (nab)-paclitaxel is a novel formulation of paclitaxel with greater dose tolerance and improved efficacy. We hypothesized that nab-paclitaxel and carboplatin would be superior to alternative doublets in advanced NSCLC patients ineligible for bevacizumab.
  
  
  METHODS
  We conducted a single-arm phase II trial (NCT00729612) with carboplatin and nab-paclitaxel on day 1 of a 21-day cycle to evaluate RR (primary end point), safety, toxicity, and OS. Eligibility included: squamous histology, hemoptysis, or ongoing anticoagulation. Correlative studies included immunohistochemistry for secreted protein acid rich in cysteine (SPARC) and caveolin-1 (Cav-1).
  
  
  RESULTS
  Sixty-three patients were enrolled. Most patients had squamous cell carcinoma (n = 48); other reasons for eligibility included hemoptysis (n = 11) and anticoagulation (n = 2). Toxicity Grade ≥ 3/4 included neuropathy, cytopenias, and fatigue. RR was 38% (24 partial response/0 complete response); 20 patients had stable disease (32%). Median progression-free survival was 5 months and median OS was 9.7 months. Immunohistochemistry for SPARC and Cav-1 was performed in 38 and 37 patients respectively. Although no association was found for SPARC expression in tumor or stroma with RR or OS, we found that higher Cav-1 levels in tumor-associated stroma was associated with improved RR and OS.
  
  
  CONCLUSIONS
  Carboplatin and nab-paclitaxel every 21 days demonstrated promising efficacy with tolerable toxicity in NSCLC patients ineligible for bevacizumab therapy. Further analysis and validation of Cav-1 and SPARC expression in tumor and stromal compartments as prognostic and/or predictive biomarkers of NSCLC or nab-paclitaxel treatment is warranted.
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Columbus, OH.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Bertino
authors.affiliation: Department of Radiation Oncology, The Ohio State University, Columbus, OH.
authors.forename: Terence M
authors.initials: TM
authors.lastname: Williams
authors.affiliation: Department of Internal Medicine, Division of Pulmonology/Critical Care, The Ohio State University, Columbus, OH.
authors.forename: S Patrick
authors.initials: SP
authors.lastname: Nana-Sinkam
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shilo
authors.affiliation: Department of Radiation Oncology, The Ohio State University, Columbus, OH.
authors.forename: Moumita
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
authors.forename: Meliha
authors.initials: M
authors.lastname: Rahmani
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Phillips
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Columbus, OH.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Villalona-Calero
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Columbus, OH. Electronic address: greg.otterson@osumc.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000737:chemistry; D000068258:Bevacizumab; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D051242:Caveolin 1 / Q000378:metabolism*; D000075202:Contraindications; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D009367:Neoplasm Staging; D009422:Nervous System Diseases / Q000209:etiology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D017154:Stromal Cells / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D000418:Albumins; D054316:Biomarkers, Pharmacological; D051242:Caveolin 1; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel
keywords: Caveolin-1; Clinical Trial; SPARC; Sensory neuropathy; nab-paclitaxel