Preliminary data of nilotinib in the first-line treatment of patients with metastatic or unresectable gastrointestinal stromal tumors (GIST).
Authors: P. G. Casali, H. Joensuu, J. Martin Broto, X. Garcia del Muro, J. Blay, C. May, A. Pustowka, P. Reichardt
Journal: Journal of Clinical Oncology (2010)

TPS332^ Background: Nilotinib (N) is a novel tyrosine kinase inhibitor (TKI) of KIT, PDGFRA, and BCR-AbL that has been shown to inhibit the proliferation of imatinib (I)-resistant GIST cell lines. Preliminary studies with N have shown that it can provide clinical activity in patients (pts) who have failed first- and second-line therapies and is safe in pts with advanced GIST. This Phase II study was conducted to investigate the efficacy of N as first-line treatment. Methods: The multicenter, single-arm trial evaluated the efficacy of N in newly diagnosed pts with unresectable or metastatic GIST or with recurrent GIST post adjuvant treatment. Pts were given N 400 mg bid until disease progression, unacceptable toxicity, or discontinuation for another reason. Primary endpoint was PFS at 6 months determined by RECIST; secondary endpoints included objective tumor response (RECIST), time to overall response, duration of response, progression-free survival, overall survival, and safety. Results: As of December 2009, a total of 21 pts were enrolled, 14 of whom had completed 6 months of treatment and were included in the efficacy analysis. Median follow-up was 176 days (range: 1–367). The study included 19 pts with metastatic GIST; there were 11 male and 8 female pts, with median age 60 years(range: 35–78). Best overall response included 6 pts with partial responses (42.9%), 6 with stable disease (42.9%), and 2 with progressive disease (14.3%). Rate of progression-free pts at 6 mo is 85.7%. Adverse events (AEs) were experienced by 57.9% of pts, including gastrointestinal disorders such as nausea, vomiting, diarrhea (42.1%) and eyelid edema (10.5%). Most AEs were grade 1 or 2 (CTCEAv3.0). No deaths occurred during the study period. Mutational data will be presented. Conclusions: In the early analysis of this pilot study, N displayed substantial clinical benefit and a favorable safety profile in the first-line treatment of patients with metastatic or unresectable GIST. Updated data will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis ARIAD, GlaxoSmithKline,Infinity, Merck, Novartis, Pfizer, PharmaMar, sanofi-aventis Novartis, Pfizer, PharmaMar Amgen, ARIAD, GlaxoSmithKline, Infinity, Johnson & Johnson, Lilly, Merck, Novartis, Pfizer, PharmaMar, sanofi-aventis, Schering-Plough Novartis, PharmaMar In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.