First-line pemetrexed plus cisplatin followed by gefitinib maintenance therapy versus gefitinib monotherapy in East Asian patients with locally advanced or metastatic non-squamous non-small cell lung cancer: A randomised, phase 3 trial
Journal
European Journal of Cancer
Journal Volume
50
Journal Issue
13
Pages
2219-2230
Date Issued
2014
Author(s)
Kang J.H.
Mok T.
Ahn M.-J.
Srimuninnimit V.
Kim D.-W.
Tsai C.-M.
Barraclough H.
Altug S.
Orlando M.
Park K.
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, chemona?ve, 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/m2) plus cisplatin (75 mg/m2) 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. ? 2014 Elsevier Ltd. All rights reserved.
SDGs
Other Subjects
antineoplastic agent; cisplatin; gefitinib; glutamic acid derivative; guanine; pemetrexed; protein kinase inhibitor; quinazoline derivative; adult; aged; analogs and derivatives; Asian continental ancestry group; Carcinoma, Non-Small-Cell Lung; clinical trial; controlled study; disease free survival; female; genetics; human; Lung Neoplasms; male; middle aged; multicenter study; pathology; phase 3 clinical trial; randomized controlled trial; very elderly; young adult; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Asian Continental Ancestry Group; Carcinoma, Non-Small-Cell Lung; Cisplatin; Disease-Free Survival; Female; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Quinazolines; Young Adult
Publisher
Elsevier Ltd
Type
journal article