To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: BMS-690514 Demonstrates Disease Control in Patients With Non-Small-Cell Lung Cancer: Presented at EORTC-NCI-AACR URL: http://www.pslgroup.com/dg/23154A.htm Doctor's Guide October 24, 2008
By Chris Berrie GENEVA -- October 24, 2008 -- The ErbB/Her2/vascular endothelial growth-factor receptor (VEGFR) inhibitor BMS-690514 is generally well tolerated and shows encouraging evidence of antitumour activity and disease control in patients with non-small-cell lung cancer (NSCLC). An interim analysis of an early, ongoing study of BMS-690514 was presented here at the 20th International Symposium of the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI), and the American Association for Cancer Research (AACR). Recent clinical studies have shown benefit for patients with NSCLC through the simultaneous inhibition of VEGFR and epidermal growth-factor receptor (EGFR) signalling. In a presentation here on October 23, principal investigator Jean-Charles Soria, MD, PhD, Gustave Roussy Institute, Villejuif, France, noted, "This is a pan-Erb inhibitor that also has a VEGFR inhibition profile, so this is quite unique…. It is reversible, and it clearly hits both targets." The primary objectives of the trial were 2-fold: Part A was the identification of the maximum tolerated dose of BMS-690514 in patients with solid tumours, and part B was assessment of disease control in patients with erlotinib-naïve and erlotinib-resistant NSCLC, with exploration of biomarkers for sensitivity to BMS-690514. Secondary objectives examined safety and pharmacokinetics of BMS-690514 and looked to demonstrate pharmacodynamic inhibition of the EGFR and VEGFR. The main eligibility criteria for part A were for adult patients with advanced solid tumours and no brain metastasis; part B focused on adult patients with advanced NSCLC, with brain metastasis allowed. Eastern Cooperative Oncology Group performance status was set for 0 to 1 in all cases, with adequate renal and hepatic function. Individuals were excluded who had uncontrolled hypertension, significant cardiovascular disease, or grade 1 electrocardiogram changes. BMS-690514 treatment started with dose escalation from 40 mg to 300 mg daily, with patient expansion to part B set for 200 mg daily. This interim analysis included a total of 42 patients in part B: 17 as erlotinib-naïve (65% male, median age 63 years) and 25 patients as erlotinib-resistant (64% male, median age 59 years). These subjects mainly demonstrated an ECOG-PS of 1 (59% naïve vs 56% resistant), with <3 prior chemotherapy regimens in 77% and 32%, respectively. Only 18% and 8%, respectively, had used a prior VEGF inhibitor. Antitumour activity was apparent from 3 partial responses for 1 patient with metastatic oesophageal carcinoma and 2 with NSCLC; stable disease was seen in a further 6 patients with erlotinib-resistant NSCLC. Dr. Soria noted in particular that these last 6 patients included 2 individuals who showed the T790M EGFR mutation, which confers resistance to erlotinib treatment. A further 5 partial responses were seen in the naïve group with NSCLC. The adverse events for the overall safety in part B were predominantly mild to moderate, including diarrhoea, rash, and hypertension, with frequency of further adverse events as expected for VEGFR inhibition. Eight patients showed 12 treatment-related serious AEs, and Dr. Soria felt that "this toxicity profile is manageable." While reporting on the pharmacodynamics of the VEGFR and EGFR in this study, Dr. Soria again stressed the efficacy with the EGFR T790M mutation, adding, "This profile is done with the diagnostic material, so it might not reflect the true percentage of T790M mutations at entry in the trial, as there was no mandatory biopsy." Funding for this study was provided by Bristol-Myers Squibb. [Presentation title: Phase 1/2 Study of BMS-690514, an ErbB-VEGFR Inhibitor: Safety, Pharmacodynamic Effects and Early Clinical Activity in Patients With Advanced Solid Tumours and Non-Small-Cell Lung Carcinoma (NSCLC). Abstract 392] --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content. --------------------------------------------------------------------------------------------- This news story was printed from *Doctor's Guide to the Internet* located at http://www.docguide.com --------------------------------------------------------------------------------------- Return to News Story Page This site is maintained by webmaster@pslgroup.com Please contact us with any comments, problems or bugs. All contents Copyright (c) 1998 P\S\L Consulting Group Inc. All rights reserved.