RESUMO
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). 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.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Genes erbB-1 , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Quinazolinas/uso terapêutico , População Branca/genética , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Progressão da Doença , Intervalo Livre de Doença , Receptores ErbB/sangue , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Vandetanib (ZACTIMA; ZD6474) is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The safety and tolerability of vandetanib plus pemetrexed was assessed in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with previously treated NSCLC (stage IIIB/IV) received once-daily oral vandetanib (100 or 300 mg) with pemetrexed (500 mg/m(2) i.v. infusion every 21 days). RESULTS: Patients received vandetanib 100 mg + pemetrexed (n=10) or vandetanib 300 mg + pemetrexed (n=11). The protocol definition of a tolerable dose [vandetanib-related dose-limiting toxicity (DLT) in less than 2 patients] was met in both dose cohorts, with one DLT reported in each: asymptomatic QTc prolongation (>100 ms increase from baseline, but absolute QTc<500 ms) in the 100 mg cohort and interstitial lung disease, which resolved after steroid therapy, in the 300 mg cohort. The most common adverse events were rash, anorexia, fatigue and diarrhea (all n=10). CONCLUSION: Vandetanib and pemetrexed in combination were generally well tolerated in patients with advanced NSCLC.
