title: Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Figitumumab (CP-751,871), a fully human immunoglobulin G2 monoclonal antibody, inhibits the insulin-like growth factor 1 receptor (IGF-1R). Our multicenter, randomized, phase III study compared figitumumab plus chemotherapy with chemotherapy alone as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with stage IIIB/IV or recurrent NSCLC disease with nonadenocarcinoma histology received open-label figitumumab (20 mg/kg) plus paclitaxel (200 mg/m(2)) and carboplatin (area under the concentration-time curve, 6 mg · min/mL) or paclitaxel and carboplatin alone once every 3 weeks for up to six cycles. The primary end point was overall survival (OS).
  
  
  RESULTS
  Of 681 randomly assigned patients, 671 received treatment. The study was closed early by an independent Data Safety Monitoring Committee because of futility and an increased incidence of serious adverse events (SAEs) and treatment-related deaths with figitumumab. Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively. The respective rates of all-causality SAEs were 66% and 51%; P < .01). Treatment-related grade 5 adverse events were also more common with figitumumab (5% v 1%; P < .01).
  
  
  CONCLUSIONS
  Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC. Further clinical development of figitumumab is not being pursued.
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China. corey.langer@uphs.upenn.edu.
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Langer
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Karp
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Benner
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Scranton
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Olszanski
authors.affiliation: Corey J. Langer, University of Pennsylvania; Anthony J. Olszanski, Fox Chase Cancer Center, Philadelphia, PA; Daniel D. Karp, MD Anderson Center, Houston, TX; Rebecca J. Benner, Judith R. Scranton, Pfizer Oncology, Groton, CT; Silvia Novello, University of Turin, Orbassano, Italy; Keunchil Park, Sungkyunkwan University School of Medicine, Seoul, Korea; Maciej Krzakowski, The Maria Sklodowska-Curie Institute of Oncology, Warsaw; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Tony Mok, Chinese University, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D016190:Carboplatin; D006442:Glycated Hemoglobin; D007334:Insulin-Like Growth Factor I; D017239:Paclitaxel; C517652:hemoglobin A1c protein, human; C525021:figitumumab