Activity of IPI-504, a Novel Heat-Shock Protein 90 Inhibitor, in Patients With Molecularly Defined Non-Small-Cell Lung Cancer

作者：Sequist Lecia V^*; Gettinger Scott; Senzer Neil N; Martins Renato G; Jaenne Pasi A; Lilenbaum Rogerio; Gray Jhanelle E; Iafrate A John; Katayama Ryohei; Hafeez Nafeeza; Sweeney Jennifer; Walker John R; Fritz Christian; Ross Robert W; Grayzel David; Engelman Jeffrey A; Borger Darrell R; Paez Guillermo; Natale Ronald

来源：Journal of Clinical Oncology, 2010, 28(33): 4953-4960.

DOI：10.1200/JCO.2010.30.8338

Purpose IPI-504 is a novel, water-soluble, potent inhibitor of heat-shock protein 90 (Hsp90). Its potential anticancer activity has been validated in preclinical in vitro and in vivo models. We studied the activity of IPI-504 after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in patients with advanced, molecularly defined non-small-cell lung cancer (NSCLC).
Patients and Methods Patients with advanced NSCLC, prior treatment with EGFR TKIs, and tumor tissue available for molecular genotyping were enrolled in this prospective, nonrandomized, multicenter, phase II study of IPI-504 monotherapy. The primary outcome was objective response rate (ORR). Secondary aims included safety, progression-free survival (PFS), and analysis of activity by molecular subtypes.
Results Seventy-six patients were enrolled between December 2007 and May 2009 from 10 United States cancer centers. An ORR of 7% (five of 76) was observed in the overall study population, 10% (four of 40) in patients who were EGFR wild-type, and 4% (one of 28) in those with EGFR mutations. Although both EGFR groups were below the target ORR of 20%, among the three patients with an ALK gene rearrangement, two had partial responses and the third had prolonged stable disease (7.2 months, 24% reduction in tumor size). The most common adverse events included grades 1 and 2 fatigue, nausea, and diarrhea. Grade 3 or higher liver function abnormalities were observed in nine patients (11.8%).
Conclusion IPI-504 has clinical activity in patients with NSCLC, particularly among patients with ALK rearrangements. J Clin Oncol 28:4953-4960.

• 出版日期2010-11-20