Yi-Long Wu1, Nagahiro Saijo2, Sumitra Thongprasert3, J C-H Yang4, Baohui Han5, Benjamin Margono6, Busayamas Chewaskulyong7, Patrapim Sunpaweravong8, Yuichiro Ohe9, Yukito Ichinose10, Jin-Ji Yang11, Tony S K Mok12, Helen Young13, Vincent Haddad14, Yuri Rukazenkov15, Masahiro Fukuoka16. 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/IVadenocarcinoma 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. Copyright Â
RCT Entities:
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. Copyright Â
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