Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer
Journal
Lung Cancer
Journal Volume
77
Journal Issue
2
Pages
346-352
Date Issued
2012
Author(s)
Abstract
Introduction: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors or chemotherapy have shown improved survival outcomes in East Asian, never-smoker patients with non-small cell lung cancer (NSCLC). However, treatment sequence has not been optimized in patients with unknown EGFR mutation status. This trial compared first-line chemotherapy with pemetrexed (P)-cisplatin (C), followed by either gefitinib (G) or P maintenance. Methods: East Asian, never-smoker, chemo-na?ve patients with stage IIIB/IV NSCLC, performance status ?1 and unknown EGFR mutation status were randomized 1:1 to receive 4 cycles of pemetrexed [500mg/m 2]+cisplatin [75mg/m 2] q3 weeks, followed by maintenance with either gefitinib [250mg/d] (PC/G) or pemetrexed [500mg/m 2] q3 weeks and ?2 optional cycles of cisplatin (PC/P). The primary endpoint, progression-free survival (PFS), was calculated from randomization date. Results: Between Feb and Nov 2007, 70 patients from China, Korea, and Taiwan were randomized and treated, among whom 59 patients (84.3%) had non-squamous NSCLC. Forty-nine patients (70.0%) completed the full sequential treatment (n= 25 G; n= 24 P). Median PFS was numerically longer for patients on PC/G (9.95 months) than those on PC/P (6.83. months; hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.27, 1.04). In contrast, median overall survival was numerically higher for patients on PC/P (HR = 2.15, 95% CI = 0.83, 5.60), though there was a high censoring rate. Response rate was similar in both arms. Treatment arms were similar for grade 3/4/5 toxicities. Conclusions: East Asian never-smoker patients with advanced NSCLC and unknown EGFR mutation status had improved PFS following treatment with first-line PC and sequential G. Irrespective of subsequent maintenance treatment, induction PC was safe and efficacious, leading to prolonged OS in the Asian patient population. ? 2012 Elsevier Ireland Ltd.
Subjects
Gefitinib; Maintenance therapy; Never-smoker; Non-small cell lung cancer; Pemetrexed; Unknown EGFR mutation status
SDGs
Other Subjects
cisplatin; cyanocobalamin; dexamethasone; epidermal growth factor receptor; folic acid; gefitinib; pemetrexed; adult; advanced cancer; aged; alanine aminotransferase blood level; anorexia; article; Asian; blood toxicity; cancer combination chemotherapy; cancer patient; chemotherapy induced emesis; China; controlled study; disease severity; drug efficacy; drug eruption; drug fatality; drug safety; drug tolerability; drug withdrawal; dyspnea; fatigue; female; gene expression; gene mutation; granulocytopenia; hazard ratio; histopathology; human; hypokalemia; hyponatremia; Korea; lung adenocarcinoma; lung non small cell cancer; major clinical study; male; metabolic disorder; multicenter study; multiple cycle treatment; nausea; neurologic disease; neutropenia; overall survival; phase 2 clinical trial; pneumonia; priority journal; progression free survival; randomized controlled trial; side effect; sudden death; Taiwan; thrombocytopenia; treatment duration; treatment outcome; treatment response; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asian Continental Ancestry Group; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Quinazolines; Treatment Outcome
Type
journal article