Gefitinib (IRESSA) in Patients of Asian Origin with Refractory Advanced Non-small Cell Lung Cancer: Subset Analysis from the ISEL Study

Abstract

Introduction:The IRESSA Survival Evaluation in Lung Cancer (ISEL) phase III study compared the efficacy of gefitinib (IRESSA) versus placebo in patients with refractory advanced non-small cell lung cancer (NSCLC). Although a statistically significant difference in survival was not seen between gefitinib and placebo in the overall ISEL population, preplanned subset analyses demonstrated a significant survival benefit in patients who had never smoked and in patients of Asian origin. Methods: In ISEL, 1692 patients who were refractory to or intolerant of their latest chemotherapy were randomized to receive either gefitinib (250 mg/day) or placebo, plus best supportive care. Preplanned subgroup analyses included an assessment of patients who were of Asian origin (n ϭ 342). Results: Two hundred thirty-five patients of Asian origin received gefitinib, and 107 received placebo. In these patients, treatment with gefitinib significantly improved survival compared with placebo (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.48, 0.91; p ϭ 0.010; median survival, 9.5 versus 5.5 months). Patients of Asian origin also experienced statistically significant improvements in time to treatment failure with gefitinib compared with placebo (HR, 0.69; 95% CI, 0.52, 0.91; p ϭ 0.0084; 4.4 versus 2.2 months), and objective response rates were higher with gefitinib than with placebo (12 versus 2%). Gefitinib was generally well tolerated in patients of Asian origin, with rash and diarrhea being the most common adverse events. No unexpected adverse events were observed. Conclusions: Treatment with gefitinib was associated with a significant improvement in survival in a subgroup of patients of Asian origin with previously treated refractory advanced NSCLC.

Early radiographic response to epidermal growth factor receptor-tyrosine kinase inhibitor in non-small cell lung cancer patients with epidermal growth factor receptor mutations: A prospective study

“…Two drugs, erlotinib (Tarceva) and gefitinib (Iressa; AstraZeneca Inc., Menchester, UK), have been shown to have survival benefit in Caucasians and Asians, respectively, when compared to placebo in controlled, double-blinded, randomized phase III trials. [3,4] These two EGFR-TKIs disrupt EGFR signaling by competing with adenosine triphosphate (ATP) for the binding sites at tyrosine kinase domain, and result in inhibition of phosphorylation and the downstream signaling network. These EGFR-TKIs are only effective to a subgroup of NSCLC patients and act faster than conventional chemotherapy, but have relatively mild side effects.…”

10.5937/mckg48-2741 = New pharmacological strategies in the treatment of non-small cell lung cancer

“…Studija ISEL (Iressa Survival Evaluation in Lung cancer) bila je studija III faze kliničkog ispitivanja 250 mg gefitiniba primenjenog kao druga ili treća linija lečenja bolesnika sa lokalno uznapredovalim ili metastatskim NSCLC rezistentnim na prethodno primljenu standardnu hemioterapiju (9). Zaključci iz ovih studija bili su da najveću korist od gefitiniba (u standardnoj dozi od 250 mg dnevno) u odnosu na placebo, imaju nepušači, žene, oboleli od adenokarcinoma i bolesnici azijske populacije.…”

TPCA-1 Is a Direct Dual Inhibitor of STAT3 and NF-κB and Regresses Mutant EGFR-Associated Human Non–Small Cell Lung Cancers

“…In addition, TKIs responsive patients also showed different sensitivity to the treatment. These findings indicated that other causes might also contribute to the intrinsic resistance (8)(9)(10). Therefore, completely understanding of the causes for responsiveness to EGFR TKIs is worth pursuing to improve the clinical benefits of targeted therapies.…”