Lee, Dae Ho; Lee, Jung Shin; Kim, Sang-We; Rodrigues-Pereira, Jose; Han, Baohui; Song, Xiang-Qun; Wang, Jie; Kim, Hoon-Kyo; Sahoo, Tarini Prasad; Digumarti, Raghunadharao; Wang, Xin; Altug, Sedat; Orlando, Mauro
European journal of cancer (Oxford, England : 1990)
2013Oct ; 49 ( 15 ) :3111-21.
PMID : 23890768
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Lee, Dae Ho -
Lee, Jung Shin -
Kim, Sang-We -
Rodrigues-Pereira, Jose -
Han, Baohui -
Song, Xiang-Qun -
Wang, Jie -
Kim, Hoon-Kyo -
Sahoo, Tarini Prasad -
Digumarti, Raghunadharao -
Wang, Xin -
Altug, Sedat -
Orlando, Mauro -
ABSTRACT
BACKGROUND: This randomised controlled phase 2 study compared pemetrexed and erlotinib in combination with either agent alone in terms of efficacy and safety as second-line treatment in a clinically selected population of never-smokers with non-squamous non-small cell lung cancer (NSCLC).
METHODS: Patients who had failed only one prior chemotherapy regimen and had Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ?? were randomised to either: pemetrexed 500 mg/m(2) on day 1 plus erlotinib 150 mg daily on days 2-14; erlotinib 150 mg daily; or pemetrexed 500 mg/m(2) on day 1 of a 21-day cycle until discontinuation criteria were met. The primary endpoint, progression-free survival (PFS), was analysed using a multivariate Cox model. Firstly, a global comparison across the three arms was performed. If the global null hypothesis was rejected at a two-sided 0.2 significance level, pairwise comparisons of pemetrexed-erlotinib versus erlotinib or pemetrexed were then conducted using the same model. Statistical significance was claimed only if both global and pairwise null hypotheses were rejected at a two-sided 0.05 significance level. FINDINGS: A total of 240 patients (male, 35%; East Asian, 55%; ECOG PS 0-1, 93%) were included. A statistically significant difference in PFS was found across the three arms (global p=0.003), with pemetrexed-erlotinib significantly better than either single agent: HR=0.57, 95% confidence interval (CI): 0.40-0.81, p=0.002 versus erlotinib; HR=0.58, 95% CI: 0.39-0.85, p=0.005 versus pemetrexed. Median PFS (95% CI) was 7.4 (4.4, 12.9) months in pemetrexed-erlotinib, 3.8 (2.7, 6.3) months in erlotinib and 4.4 (3.0, 6.0) months in pemetrexed. Safety analyses showed a higher incidence of drug-related grade 3/4 toxicity in pemetrexed-erlotinib (60.0%) than in pemetrexed (28.9%) or erlotinib (12.0%); the majority being neutropenia, anaemia, rash and diarrhoea. INTERPRETATION: Pemetrexed-erlotinib significantly improved PFS compared to either drug alone in this clinically selected population. The combination had more toxicity, but was clinically manageable. CI - Copyright ??2013 Elsevier Ltd. All rights reserved.
keyword
Erlotinib; Never smoker; Non-small cell lung cancer; Pemetrexed; Phase 2
MESH
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Carcinoma, Non-Small-Cell Lung/*drug therapy, Disease Progression, Disease-Free Survival, Erlotinib Hydrochloride, Female, Glutamates/administration & dosage/adverse effects/*therapeutic use, Guanine/administration & dosage/adverse effects/*analogs &, Humans, Lung Neoplasms/*drug therapy, Male, Middle Aged, Pemetrexed, Proportional Hazards Models, Quinazolines/administration & dosage/adverse effects/*therapeutic use
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