Yang, James Chih-Hsin; Kang, Jin Hyoung; Mok, Tony; Ahn, Myung-Ju; Srimuninnimit, Vichien; Lin, Chia-Chi; Kim, Dong-Wan; Tsai, Chun-Ming; Barraclough, Helen; Altug, Sedat; Orlando, Mauro; Park, Keunchil
European journal of cancer (Oxford, England : 1990)
2014Sep ; 50 ( 13 ) :2219-30.
PMID : 24953333
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Yang, James Chih-Hsin - National Taiwan University Hospital, Taipei, Taiwan.
Kang, Jin Hyoung - The Catholic University of Korea, St. Mary's Hospital, Seoul, Republic of Korea.
Mok, Tony - State Key Laboratory of South China, Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong.
Ahn, Myung-Ju - Samsung Medical Center, Seoul, Republic of Korea.
Srimuninnimit, Vichien - Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Lin, Chia-Chi - National Taiwan University Hospital, Taipei, Taiwan.
Kim, Dong-Wan - Seoul National University Hospital, Seoul, Republic of Korea.
Tsai, Chun-Ming - Taipei Veterans General Hospital, Taipei, Taiwan.
Barraclough, Helen - Eli Lilly and Company Australia, Australia.
Altug, Sedat - Eli Lilly and Company Turkey, Turkey.
Orlando, Mauro - Eli Lilly and Company Interamerica, Argentina.
Park, Keunchil - Samsung Medical Center, Seoul, Republic of Korea. Electronic address keunchil.park@samsung.com.
ABSTRACT
BACKGROUND: In the Iressa Pan-ASia Study (IPASS), gefitinib claimed improved progression-free survival (PFS) versus carboplatin-paclitaxel in clinically selected lung cancer patients. The primary objective of this study was to assess the PFS of pemetrexed-cisplatin (PC) followed by gefitinib maintenance versus gefitinib monotherapy in an IPASS-like population.
METHODS: In this open-label, randomised, phase 3 trial, eligible patients were ?18 years, chemonaive, East Asian, light ex-smokers/never-smokers with advanced non-squamous non-small cell lung cancer, an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and unknown epidermal growth factor receptor (EGFR) mutation status who enrolled at 12 sites in Asia. Patients randomly received (1:1) pemetrexed (500 mg/m(2)) plus cisplatin (75mg/m(2)) for six 21-day cycles, followed by gefitinib maintenance or gefitinib monotherapy (250 mg/day). Patient tissue was retrospectively analysed for EGFR mutations. This study is registered with ClinicalTrials.gov, NCT01017874. FINDINGS: Between 23rd November 2009 and 27th April 2012, 253 patients entered, and 236 patients were randomly assigned to and treated with PC therapy (N=114) and gefitinib monotherapy (N=118). Between-arm baseline characteristics were balanced. PFS was not significantly different between treatment arms (p=0.217). The unadjusted hazard ratio (HR) was 0.85 (95% confidence interval (CI) 0.63-1.13). The HR should be cautiously interpreted as it was not constant. EGFR mutation status was determined for 74 tissue samples; 50 (67.6%) had mutations. In a pre-specified subgroup analysis, only the treatment-by-EGFR mutation interaction was significant (p=0.008) for PFS. For the entire treatment period, a higher proportion of patients in the PC/gefitinib arm versus gefitinib experienced possibly drug-related grade 3-4 treatment-emergent adverse events (39 of 114 [34%] versus 19 of 118 [16%]; p=0.002). INTERPRETATION: In the intention-to-treat (ITT) population, PFS was not significantly different. In the biomarker-assessable population, front-line EGFR tyrosine kinase inhibitor monotherapy was not efficacious in patients with wild-type EGFR. Identification of EGFR mutation status is key in the management of advanced non-squamous non-small cell lung cancer. FUNDING: Eli Lilly and Company. CI - Copyright ??2014 Elsevier Ltd. All rights reserved.
keyword
Cisplatin; East Asian patients; Gefitinib; Non-squamous non-small cell lung cancer; Pemetrexed
MESH
Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Asian Continental Ancestry Group/genetics, Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology, Cisplatin/administration & dosage, Disease-Free Survival, Female, Glutamates/administration & dosage, Guanine/administration & dosage/analogs & derivatives, Humans, Lung Neoplasms/*drug therapy/pathology, Male, Middle Aged, Pemetrexed, Protein Kinase Inhibitors/administration & dosage/therapeutic use, Quinazolines/administration & dosage/*therapeutic use, Young Adult
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