First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study

Abstract

Background:Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).Methods:Treatment: gefitinib 250 mg day−1 until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples.Results:Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8% adenocarcinoma 97.2% never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5–77.7), DCR 90.6% (95% CI 83.5–94.8), median PFS 9.7 months (95% CI 8.5–11.0), median OS 19.2 months (95% CI 17.0–NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15% SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8–74.7).Conclusion:First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.

Tyrosine kinase inhibitors for EGFR- and ALK-mutated non-small cell lung cancer

“…The approval was based on a phase IV study of gefitinib for first-line treatment of Caucasian patients with exon 19 or L858R EGFR mutations. In the 106 patients in this study, the overall response rate was 69.8 % with a median PFS of 9.7 months and median OS of 19.2 months [5].…”

“…Grade 3 or 4 transaminitis occurs in up to 11 % of patients. Rare fatal hepatotoxicity and interstitial pneumonitis have occurred with gefitinib [59,60,63,64]. [56].…”

“…Protein kinase inhibitors that target these mutations improve response rates and survival compared to standard systemic chemotherapy. The most common clinically relevant "driver" mutations encountered are the epidermal growth factor receptor (EGFR) activating mutations, which are present in 30-40 % of Asian NSCLC patients and 10 % of Caucasian patients with NSCLC [4,5]. Rearrangements in the anaplastic lymphoma kinase (ALK) gene lead to fusion proteins, which drive cellular proliferation.…”

Favorable Response of Advanced Superior Sulcus Non-Small Cell Lung Carcinoma to Gefitinib for 11 years complicated by Interval Development of Small Cell Carcinoma of the Lung

“…The patients randomly assigned to receive gefitinib had better progression-free survival than patients receiving standard chemotherapy (such as four to six cycles of carboplatin/paclitaxel). 6 Thus, the current approval is for a patient population, notably EGFR mutation-positive patients who were previously untreated, which is different than that of the 2003 approval.…”

A potential new therapeutic option for patients with advanced EGFR mutation-positive non-small cell lung cancer in first-line setting

“…Gefitinib, an orally active, selective and reversible EGFR-TKI, had been largely studied and developed for treatment in first-line setting of patients with advanced EGFR mutation-positive NSCLC compared with chemotherapy (3,4) both in Caucasian and non-Caucasian patients (5)(6)(7).…”