ArticlesGefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial
Introduction
National and international treatment guidelines for unselected patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) recommend four to six cycles of first-line platinum-based doublet chemotherapy.1, 2 However, about only 20–35% of patients respond, and median overall survival is roughly 10 months.3, 4 Second-line therapy is recommended only once a patient has progressive disease.1, 2 However, a substantial proportion of patients might not be suitable to receive further treatment, and results of studies5, 6, 7 show that only 50–70% of patients get second-line treatment.
Investigations have established the role of maintenance therapy in patients who attained tumour control with first-line chemotherapy. Ciuleanu and co-workers' study6 of maintenance pemetrexed reported improvements in progression-free and overall survival compared with placebo, mainly in patients with tumours of non-squamous histology.6 Cappuzzo and colleagues' SATURN study similarly showed a significant prolongation of progression-free survival with maintenance erlotinib compared with placebo.8 As a result of these and other findings, pemetrexed (for patients with tumours of non-squamous histology) and erlotinib (for patients with stable disease) are now licensed for maintenance treatment of advanced NSCLC in Europe and the USA.1, 2
Gefitinib, an EGFR–tyrosine-kinase inhibitor (TKI), is a standard first-line treatment for patients with advanced NSCLC whose tumours have activating EGFR mutations and has been associated with prolonged progression-free survival and improved tolerability and health-related quality of life compared with platinum-based doublet chemotherapy.9, 10, 11, 12 Gefitinib is therefore a good candidate for maintenance treatment of advanced NSCLC, as suggested by previous exploratory findings.13, 14
We postulated that maintenance therapy with gefitinib would improve progression-free survival compared with placebo for patients with advanced NSCLC who had achieved disease control after first-line platinum-based doublet chemotherapy. We aimed to establish the efficacy and tolerability of maintenance gefitinib in patients from east Asia with advanced NSCLC. Subgroup analyses in patients tested for EGFR mutations were also done.
Section snippets
Study design and patients
The Iressa in NSCLC FOR Maintenance (INFORM; Chinese Thoracic ONcology Group C-TONG 0804) study was a double-blind, randomised, placebo-controlled study of gefitinib (250 mg per day) as maintenance treatment in patients from China with locally advanced or metastatic NSCLC who had achieved disease control after first-line platinum-based doublet chemotherapy. The trial was done in 27 centres across China. Eligible patients were 18 years or older and had a life expectancy of more than 12 weeks,
Results
Between Sept 28, 2008, and Aug 11, 2009, 296 patients from 27 centres across China were randomly assigned to receive either gefitinib or placebo (ITT; n=148 both groups) (figure 1). Baseline demographic and patient characteristics were balanced between the two treatment groups (table 1). Among the 296 enrolled patients, 160 (54%) were never-smokers, 209 (71%) had adenocarcinoma histology, and 121 (41%) were female. In total, 126 (43%) patients had received taxane-based first-line chemotherapy
Discussion
The results of our investigation showed significant prolongation of progression-free survival and improvement in the proportion of patients with objective responses or disease control, and symptom control with maintenance gefitinib compared with placebo in east Asian patients with NSCLC (panel). Adverse events with gefitinib were consistent with the drug's known safety profile. Our study confirms the suggestive findings of previously published EGFR–TKI maintenance studies in patients with
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The Pharmacokinetics of Gefitinib in a Chinese Cancer Population Group: A Virtual Clinical Trials Population Study
2021, Journal of Pharmaceutical SciencesCitation Excerpt :Whilst this may be beneficial for therapy, NSCLC patients with activating epidermal growth factor receptor (EGFR) mutants tend to be highly responsive for gefitinib,54,71 and potentially up to 50 times as sensitive.72 Furthermore, a common adverse reaction is a gefitinib-induced rash which can occur at frequency of between 30% - 87%, with a severe form having an incidence of 7−22%, and which can result in treatment cessation.71,73 For PM subjects, at such increased trough gefitinib plasma concentrations, the incidence of skin rashes may be high,15 albeit it with a lower risk within the Chinese population due to low frequencies of the PM phenotype.
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For all investigators see appendix