title: An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer.
abstract: The combination of necitumumab with gemcitabine-cisplatin significantly improved overall survival (OS) in patients with stage IV squamous non-small-cell lung cancer (NSCLC), in the phase III SQUamous NSCLC treatment with the Inhibitor of EGF REceptor (SQUIRE) trial. Paclitaxel-carboplatin was selected as an alternative standard of care in the current phase II study.
  
  
  
  Patients were randomized (stratified according to Eastern Cooperative Oncology Group performance status and sex) 2:1 to ≤ six 3-week cycles (Q3W) of paclitaxel and carboplatin with or without necitumumab. Chemotherapy was paclitaxel 200 mg/m2on day 1 Q3W and carboplatin area under the curve 6 on day 1 Q3W. Necitumumab 800 mg, on days 1 and 8, was continued until disease progression or intolerable toxicity occurred. The primary end point was objective response rate (ORR) on the basis of Response Evaluation Criteria In Solid Tumors version 1.1.
  
  
  
  One hundred sixty-seven patients were randomized to the necitumumab-containing arm (n = 110) or the chemotherapy-only arm (n = 57). The combination of necitumumab with chemotherapy resulted in an ORR of 48.9% versus 40.0%. Median progression-free survival and OS were 5.4 versus 5.6 months (hazard ratio [HR], 1.0) and 13.2 versus 11.2 months (HR, 0.83; P = .379) in each treatment arm, respectively. Disease control rate was 87.2% versus 84.0%. Grade ≥ 3 adverse events typically associated with epidermal growth factor receptor (EGFR) monoclonal antibodies showing a > 2% increase were hypomagnesemia (5.7% vs. 0) and rash (2.8% vs. 0). Any Grade thromboembolic events occurred in < 4% of patients in either arm.
  
  
  
  The results of our study support previously reported results that the combination of necitumumab with chemotherapy improves survival in patients with advanced squamous NSCLC and shows a safety profile consistent with that of EGFR monoclonal antibodies.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN. Electronic address: dspigel@tnonc.com.
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.affiliation: Leningrad Regional Clinical Hospital, St Petersburg, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Luft
authors.affiliation: Lilly Deutschland, Bad Homburg, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Depenbrock
authors.affiliation: Department of Oncology, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.affiliation: Clopton Clinic, Jonesboro, AR.
authors.forename: Mazen
authors.initials: M
authors.lastname: Khalil
authors.affiliation: CHA Bundang Medical Center, CHA University, Gyeonggi-do, Korea.
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Eli Lilly and Company, Bridgewater, NJ.
authors.forename: Carlos
authors.initials: C
authors.lastname: Mayo
authors.affiliation: Eli Lilly and Company, Bridgewater, NJ.
authors.forename: Grace Yi
authors.initials: GY
authors.lastname: Chao
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Coleman
authors.initials: C
authors.lastname: Obasaju
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Natale
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D066066:Response Evaluation Criteria in Solid Tumors; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C527969:necitumumab; D016190:Carboplatin; D017239:Paclitaxel
keywords: Anti-EGFR; Efficacy; Monoclonal antibody; Safety; Targeted therapy