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Lung Cancer. 2017 Feb;104:119-125. doi: 10.1016/j.lungcan.2016.11.022. Epub 2016 Nov 30.

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.

Author information

1
Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou 510080, China. Electronic address: syylwu@live.cn.
2
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.
3
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.
4
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.
5
Department of Respiratory Disease, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China. Electronic address: xkyyhan@gmail.com.
6
Jl. Mayjend Prof. Dr. Moestopo No. 6-8 Surabaya, Jawa Timur 60285, Indonesia. Electronic address: bmargono@yahoo.com.
7
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.
8
Songklanagarind Hospital, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla 90110, Thailand. Electronic address: sunpawep@myumanitoba.ca.
9
Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chou-ku, Tokyo 104-0045, Japan. Electronic address: yohe@ncc.go.jp.
10
National Hospital Organization Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka 811-1395, Japan. Electronic address: ichinose.yukito@gmail.com.
11
Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou 510080, China. Electronic address: yangjinji2003@163.com.
12
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.
13
(Formerly of) AstraZeneca, 310 Cambridge Science Park, Milton Road, Cambridge, Cambridgeshire, CB4 0FZ, United Kingdom. Electronic address: hhyoung@btinternet.com.
14
AstraZeneca, Da Vinci Building, Melbourn Science Park, Cambridge Road, Melbourn, Royston, Hertfordshire, SG8 6HB, United Kingdom. Electronic address: vincent.haddad@astrazeneca.com.
15
AstraZeneca, Mereside, Alderley Park, Macclesfield, SK10 4TG, United Kingdom. Electronic address: yuri.rukazenkov@astrazeneca.com.
16
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.

Abstract

OBJECTIVE:

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.

PATIENTS AND METHODS:

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).

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

Epidermal growth factor receptor tyrosine kinase inhibitor; Epidermal growth factor receptor-mutation positive; IPASS study; Non-small-cell lung cancer

PMID:
28212993
DOI:
10.1016/j.lungcan.2016.11.022
[Indexed for MEDLINE]
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