First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study.

Abstract

BACKGROUND:

The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS:

Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.

RESULTS:

A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.

CONCLUSION:

These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

• Authors: Y-L Wu, C Zhou, C-K Liam, G Wu, X Liu, Z Zhong, S Lu, Y Cheng, B Han, L Chen, C Huang, S Qin, Y Zhu, H Pan, H Liang, E Li, G Jiang, S H How, M C L Fernando, Y Zhang, F Xia, Y Zuo
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 26 Issue 9 Pg. 1883-1889 (Sep 2015) ISSN: 1569-8041 [Electronic] England
• PMID: 26105600 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Deoxycytidine
• Carboplatin
• Erlotinib Hydrochloride
• EGFR protein, human
• ErbB Receptors
• Gemcitabine

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Asian People
• Carboplatin (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, mortality)
• Deoxycytidine (adverse effects, analogs & derivatives, therapeutic use)
• Disease-Free Survival
• ErbB Receptors (antagonists & inhibitors, genetics)
• Erlotinib Hydrochloride (adverse effects, therapeutic use)
• Female
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, genetics, mortality)
• Male
• Middle Aged
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Survival Analysis
• Treatment Outcome
• Gemcitabine