title: Efficacy according to blind independent central review: Post-hoc analyses from the phase III, randomized, multicenter, IPASS study of first-line gefitinib versus carboplatin/paclitaxel in Asian patients with EGFR mutation-positive advanced NSCLC.
abstract: The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR mutation-negative NSCLC. We report post-hoc analyses of IPASS data by blind independent central review (BICR), performed at the request of the US FDA, in a subset of patients with EGFR mutation-positive NSCLC.
  
  
  
  Eligible patients (aged ≥18 years; histologically/cytologically confirmed Stage IIB/IV adenocarcinoma NSCLC; non- or former light-smokers; treatment-naïve) were randomly assigned 1:1 to gefitinib (250mg/day) or carboplatin (dose calculated to produce an area under the curve of 5 or 6 mg/mL/minute)/paclitaxel (200mg/m2). Primary endpoint: PFS. BICR analyses included PFS, ORR, and duration of response (DoR).
  
  
  
  Scans from 186 IPASS patients (gefitinib n=88, carboplatin/paclitaxel n=98) with EGFR mutation-positive NSCLC were available for BICR. Consistent with investigator-assessed results, in patients with EGFR mutation-positive NSCLC: PFS (hazard ratio 0.54; 95% confidence interval [CI] 0.38, 0.79; p=0.0012) and ORR (odds ratio 3.00; 95% CI 1.63, 5.54; p=0.0004) were significantly longer with gefitinib versus carboplatin/paclitaxel. The median DoR by BICR was 9.6 months with gefitinib and 5.5 months with carboplatin/paclitaxel.
  
  
  
  BICR analysis of IPASS data support the original, investigator-assessed results. EGFR mutation-positive status remains a significant predictor of response to first-line TKI therapy.
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou 510080, China. Electronic address: syylwu@live.cn.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Medical Oncology Division, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka 589 8511, Japan. Electronic address: saijo@jsmo.or.jp.
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.affiliation: Medical Oncology Unit, Department of Medicine, Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University, 110 Intavaroros Road, Muang, Chiang Mai 50200, Thailand. Electronic address: sumitra95@gmail.com.
authors.forename: Sumitra
authors.initials: S
authors.lastname: Thongprasert
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. Electronic address: chihyang@ntu.edu.tw.
authors.forename: J C-H
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Department of Respiratory Disease, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China. Electronic address: xkyyhan@gmail.com.
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
authors.affiliation: Jl. Mayjend Prof. Dr. Moestopo No. 6-8 Surabaya, Jawa Timur 60285, Indonesia. Electronic address: bmargono@yahoo.com.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Margono
authors.affiliation: Medical Oncology Unit, Department of Medicine, Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University, 110 Intavaroros Road, Muang, Chiang Mai 50200, Thailand. Electronic address: bchewask@gmail.com.
authors.forename: Busayamas
authors.initials: B
authors.lastname: Chewaskulyong
authors.affiliation: Songklanagarind Hospital, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla 90110, Thailand. Electronic address: sunpawep@myumanitoba.ca.
authors.forename: Patrapim
authors.initials: P
authors.lastname: Sunpaweravong
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chou-ku, Tokyo 104-0045, Japan. Electronic address: yohe@ncc.go.jp.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.affiliation: National Hospital Organization Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka 811-1395, Japan. Electronic address: ichinose.yukito@gmail.com.
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou 510080, China. Electronic address: yangjinji2003@163.com.
authors.forename: Jin-Ji
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Sha Tin, New Territories, Hong Kong, China. Electronic address: tony@clo.cuhk.edu.hk.
authors.forename: Tony S K
authors.initials: TS
authors.lastname: Mok
authors.affiliation: (Formerly of) AstraZeneca, 310 Cambridge Science Park, Milton Road, Cambridge, Cambridgeshire, CB4 0FZ, United Kingdom. Electronic address: hhyoung@btinternet.com.
authors.forename: Helen
authors.initials: H
authors.lastname: Young
authors.affiliation: AstraZeneca, Da Vinci Building, Melbourn Science Park, Cambridge Road, Melbourn, Royston, Hertfordshire, SG8 6HB, United Kingdom. Electronic address: vincent.haddad@astrazeneca.com.
authors.forename: Vincent
authors.initials: V
authors.lastname: Haddad
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield, SK10 4TG, United Kingdom. Electronic address: yuri.rukazenkov@astrazeneca.com.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Rukazenkov
authors.affiliation: Medical Oncology Division, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka 589 8511, Japan. Electronic address: fukuoka@izumi-hp.com.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D012907:Smoking / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D016190:Carboplatin; D066246:ErbB Receptors; D017239:Paclitaxel; D000077156:Gefitinib
keywords: Epidermal growth factor receptor tyrosine kinase inhibitor; Epidermal growth factor receptor-mutation positive; IPASS study; Non-small-cell lung cancer