Phase IV study of gefitinib used as first-line treatment in Caucasian patients with epidermal growth factor receptor (EGFR) mutation-positive locally advanced/metastatic non-small cell lung cancer (NSCLC) indicate the treatment is effective and well tolerated.

The findings were presented by Dr Jean-Yves Douillard, professor of medical oncology at University of Nantes and Department of Medical Oncology, Institut de Cancérologie de l’Ouest - René Gauducheau, St Herblain, France on behalf of multinational investigators team at the European Multidisciplinary Conference in Thoracic Oncology (EMCTO).

Gefitinib is a tyrosine kinase inhibitor (TKI) of EGFR that originally showed superior efficacy in trials conducted with non-selected Asian patients. Later, molecular selection was used to enrol EGFR mutated patients in trials and reports began to appear that gefitinib was effective in patients with NSCLC of all races who had mutated EGFR.

This prospective multinational study (NCT01203917) characterises the efficacy and safety/tolerability of gefitinib for first-line treatment of Caucasian patients with EGFR mutation-positive locally advanced/metastatic NSCLC. To be eligible for this study patients were required to be Caucasian, 18 years of age or older, with a performance status 0-2 and have histologically confirmed, previously untreated stage IIIA/B/IV EGFR mutation-positive NSCLC. It was required to provide tumour tissue and matched plasma samples. Patients received gefitinib at 250 mg once daily until disease progression, which was assessed every six weeks using RECIST 1.1 criteria.

The primary endpoint of the study was objective response rate (ORR) by investigator assessment of the full analysis set (FAS). Secondary endpoints included disease control rate (DCR), defined as complete/partial response or stable disease lasting six or more weeks, progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objectives included comparison of EGFR mutation status between matched tumour and plasma samples.

In all, 1060 patients from 13 countries were screened between September 2010 and February 2012 which yielded in the FAS 106 patients with EGFR mutation-positive NSCLC.

The patients were 71% female, 97% had adenocarcinoma and the majority (64%) were never smokers.

Baseline analysis determined 31% of patients with L858R mutation, 65% of patients had exon 19 deletions and 4% of patients harboured other mutations.

At data cut off on 15 August, 2012, the primary endpoint ORR in the FAS was 70% and the DCR was 91%. Patients achieved median PFS of 9.7 months and median OS was 19 months (95%CI 17-not calculable, 27% maturity).

Analysis of evaluable samples showed a post treatment mutation rate of 13.7% in tumour and 10.5% in plasma samples. The concordance rate regarding EGFR mutation status between tumour and plasma was 94%.

Gefitinib was well tolerated overall: 8% of patients discontinued treatment due to adverse events. Incidence of serious adverse events was 19%; grades 3/4 adverse events were seen in 15% of patients. The most common adverse events of any grade included rash and diarrhoea which were seen in 45% and 31% of patients, respectively.

From these results, the authors concluded that gefitinib was effective and well tolerated as first-line treatment in Caucasian patients with EGFR mutation-positive NSCLC, as assessed by the study primary endpoint.

The study discussant, Dr Elisabeth Quoix, said that the EGFR mutation rate in Caucasian populations seems to be around 11% to 18% versus 50% in Asian populations with lung adenocarcinoma. Besides lower mutation rate compared to Asian patients there are some similarities, e.g. predominance of exon 19 deletions over exon 21 L858R substitutions, possibly better results in case of exon 19 deletions, overall response rate is around 70% and progression-free survival around 9.2 months in both populations. The current study examined mutation rate and studied gefitinib in broader European population than the study of erlotinib by Rosell and colleagues, which results have been published last year.

Dr Douillard disclosed receiving principal investigator compensation from AstraZeneca for protocol revision, he also participates in AstraZeneca Advisory Board and meeting symposia. The study co-authors McCormack, Webster and Lilenkova are employees and shareholders of AstraZeneca. All other authors have declared no conflicts of interest. Editorial assistance was provided and funded by AstraZeneca.

Source: ESMO