Dataset Information

A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer.

ABSTRACT: BACKGROUND:ASP8273, a novel, small molecule, irreversible tyrosine kinase inhibitor (TKI) specifically inhibits the epidermal growth factor receptor (EGFR) in patients with activating mutations or EGFR T790M resistance mutations. The current study examines the efficacy, safety, and tolerability of ASP8273 versus erlotinib or gefitinib in patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations not previously treated with an EGFR inhibitor. PATIENTS AND METHODS:This global, phase III, open-label, randomized study evaluated ASP8273 versus erlotinib/gefitinib in patients with locally advanced, metastatic, or unresectable stage IIIB/IV NSCLC with activating EGFR mutations. They were ineligible if they received prior chemotherapy for metastatic disease. The primary end point was progression-free survival (PFS), and secondary end points included overall survival, investigator-assessed PFS, best overall response rate (ORR), disease control rate, duration of response (DoR), and the safety/tolerability profile. RESULTS:Patients (n?=?530) were randomized 1 : 1 to receive ASP8273 (n?=?267) or erlotinib/gefitinib (n?=?263). Patient demographics between both treatment groups were generally balanced. Median PFS was 9.3?months (95% CI 5.6-11.1?months) for patients receiving ASP8273 and 9.6?months (95% CI 8.8-NE) for the erlotinib/gefitinib group, with a hazard ratio of 1.611 (P?=?0.992). The ORR in the ASP8273 group was 33% (95% CI 27.4-39.0) versus 47.9% (95% CI 41.7-54.1) in the erlotinib/gefitinib group. Median DoR was similar for both groups (9.2?months for ASP8273 versus 9.0?months for erlotinib/gefitinib). More grade ?3 treatment-emergent adverse events (TEAEs) occurred in patients receiving ASP8273 than in those receiving erlotinib/gefitinib (54.7% versus 43.5%). An independent data monitoring committee carried out an interim safety analysis and recommended discontinuing the study due to toxicity and limited predicted efficacy of ASP8273 relative to erlotinib/gefitinib. CONCLUSIONS:First-line ASP8273 did not show improved PFS or equivalent toxicities versus erlotinib/gefitinib. CLINICALTRIAL.GOV NUMBER:NCT02588261.

SUBMITTER: Kelly RJ

PROVIDER: S-EPMC6736319 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer.

Kelly R J RJ Shepherd F A FA Krivoshik A A Jie F F Horn L L

Annals of oncology : official journal of the European Society for Medical Oncology 20190701 7

<h4>Background</h4>ASP8273, a novel, small molecule, irreversible tyrosine kinase inhibitor (TKI) specifically inhibits the epidermal growth factor receptor (EGFR) in patients with activating mutations or EGFR T790M resistance mutations. The current study examines the efficacy, safety, and tolerability of ASP8273 versus erlotinib or gefitinib in patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations not previously treated with an EGFR inhibitor.<h4>Patients and methods</ ...[more]

PMID: 31070709

Similar Datasets

Project description:BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), gefitinib and erlotinib have been tested as maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC). The studies are quite heterogenous regarding study size and populations, and a synopsis of these data could give some more insight in the role of maintenance therapy with TKI.MethodsIn September 2012 we performed a search in the pubmed, EMBASE and Cochrane library databases for randomized phase III trials exploring the role of gefitinib or erlotinib in advanced non-small cell lung cancer. Through a rigorous selection process with specific criteria, five trials (n = 2436 patients) were included for analysis. Standard statistical methods for meta-analysis were applied.ResultsTKIs (gefitinib and erlotinib) significantly increased progression-free survival (PFS) [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.50-0.76, I(2) = 78.1%] and overall survival (HR 0.84, 95% CI 0.76-0.93, I(2) = 0.0%) compared with placebo or observation. The PFS benefit was consistent in all subgroups including stage, sex, ethnicity, performance status, smoking status, histology, EGFR mutation status, and previous response to chemotherapy. Patients with clinical features such as female, never smoker, adenocarcinoma, Asian ethnicity and EGFR mutation positive had more pronounced PFS benefit. Overall survival benefit was observed in patients with clinical features such as female, non-smoker, smoker, adenocarcinoma, and previous stable to induction chemotherapy. Severe adverse events were not frequent. Main limitations of this analysis are that it is not based on individual patient data, and not all studies provided detailed subgroups analysis.ConclusionsThe results show that maintenance therapy with erlotinib or gefitinib produces a significant PFS and OS benefit for unselected patients with advanced NSCLC compared with placebo or observation. Given the less toxicity of TKIs than chemotherapy and simple oral administration, this treatment strategy seems to be of important clinical value.

Dataset Information

A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer.

Publications

A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets