Association between anaplastic lymphoma kinase rearrangements (rALK) and the clinical activity of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in patients with non-small cell lung cancer (NSCLC).
2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2010.28.15_suppl.7517
ISSN1527-7755
AutoresLecia V. Sequist, Ronald B. Natale, Neil Senzer, R. G. Martins, Rogério Lilenbaum, Jhanelle E. Gray, Darrell R. Borger, Guillermo Paez, David Grayzel, Scott Gettinger,
Tópico(s)Cancer Treatment and Pharmacology
Resumo7517 Background: Oncogenic ALK gene rearrangements (rALK) recently have been identified in approximately 3-5% of all NSCLC, particularly in non-smoking patients (pts) with epidermal growth factor receptor (EGFR) wild-type tumors. IPI-504 is a potent, water-soluble heat shock protein 90 (Hsp90) inhibitor that is being evaluated in a clinical study of patients with NSCLC, stratified by EGFR status. In preclinical models, ALK is a client protein of the Hsp90 chaperone; therefore, a retrospective analysis of the ALK status of pts in this trial was conducted. Methods: A nonrandomized phase II trial investigating the safety and antitumor activity of IPI-504 as a single agent was performed. Eligible pts had advanced NSCLC that progressed after treatment with at least one tyrosine kinase inhibitor. The primary endpoint was response rate, assessed via central, independent radiology review. rALK was assessed centrally with a fluorescent in situ hybridization (FISH) break-apart assay. Results: 76 pts were enrolled. 15 pts had tissue available for analysis of the ALK gene. See Table below. Conclusions: rALK may be a useful biomarker predicting response to therapy with IPI-504. These clinical data are the first to suggest that NSCLC pts with rALK may preferentially respond to Hsp90 inhibition. Validation is ongoing in a prospective extension of this clinical trial. Clinical activity based on molecular characterization N ORR CBR Overall 76 5 (6.6%) 20 (26.3%) EGFR mutant 24 1 (4.2%) 8 (33.4%) EGFR wild type 42 4 (9.5%) 12 (28.5%) EGFR unknown 10 0 0 Known ALK fusion status 15 3 (20%) 6 (40%) rALK positive 3 2 (66.7%) 3 (100%) rALK negative 12 1 (8.3%) 3 (25%) Abbreviations: ORR, overall response rate (all partial responses); CBR, clinical benefit rate (partial response or stable disease maintained for at least 12 weeks). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Infinity Infinity Infinity
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