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Clin Cancer Res. 2013 Jun 1;19(11):3068-77. doi: 10.1158/1078-0432.CCR-12-3381. Epub 2013 Apr 3.

A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer.

Author information

  • 1University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA. socinskima@upmc.edu

Abstract

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).

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.

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-naïve 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.

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.

©2013 AACR

PMID:
23553849
[PubMed - indexed for MEDLINE]
PMCID:
PMC3874465
Free PMC Article
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