A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non-Small Cell Lung Cancer

作者：Socinski Mark A^*; Goldman Jonathan; El Hariry Iman; Koczywas Marianna; Vukovic Vojo; Horn Leora; Paschold Eugene; Salgia Ravi; West Howard; Sequist Lecia V; Bonomi Philip; Brahmer Julie; Chen Lin Chi; Sandler Alan; Belani Chandra P; Webb Timothy; Harper Harry; Huberman Mark; Ramalingam Suresh; Wong Kwok Kin; Teofilovici Florentina; Guo Wei; Shapiro Geoffrey I

来源：Clinical Cancer Research, 2013, 19(11): 3068-3077.

DOI：10.1158/1078-0432.CCR-12-3381

Purpose: Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated patients with non-small cell lung cancer (NSCLC). %26lt;br%26gt;Experimental Design: Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m(2) ganetespib by intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until disease progression. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies. %26lt;br%26gt;Results: Ninety-nine patients with a median of 2 prior systemic therapies were enrolled; 98 were assigned to cohort A (n = 15), B (n = 17), or C (n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively. Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n 1) or PCR-based assays (n = 3), in crizotinib-naive patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The most common AEs were diarrhea, fatigue, nausea, and anorexia. %26lt;br%26gt;Conclusions: Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement.

• 出版日期2013-6-1