A phase II open-label study of ganetespib, a novel heat shock protein 90 inhibitor for patients with Metastatic breast cancer

Komal Jhaveri, Sarat Chandarlapaty, Diana Lake, Teresa Gilewski, Mark Robson, Shari Goldfarb, Pamela Drullinsky, Steven Sugarman, Carolyn Wasserheit-Leiblich, Julie Fasano, Mary Ellen Moynahan, Gabriella D'Andrea, Kristina Lim, Laura Reddington, Sofia Haque, Sujata Patil, Lynne Bauman, Vojo Vukovic, Iman El-Hariry, Clifford HudisShanu Modi

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77 Scopus citations

Abstract

Background Ganetespib is a small molecule, nongeldanamycin HSP90 inhibitor with potent inhibitory effects on HSP90-dependent oncoproteins of relevance to breast cancer pathogenesis. We therefore tested ganetespib in an unselected cohort of patients with MBC. Patients and Methods Patients were treated with single agent ganetespib at 200 mg/m2 once weekly for 3 weeks, on a 28-day cycle. Therapy was continued until disease progression. The primary end point was ORR using Reponse Evaluation Criteria in Solid Tumors version 1.1. Results Twenty-two patients were enrolled with a median age of 51(range, 38-70) years and a median Eastern Cooperative Oncology Group performance status of 0 (range, 0-1). Most patients had at least 2 previous lines of chemotherapy in the metastatic setting. Most common toxicities, largely grade 1/2, were diarrhea, fatigue, nausea, and hypersensitivity reaction. The ORR in this unselected population was 9%, with all responses coming from the subset of patients with HER2-positive MBC (2/13; 15%). One patient with TNBC had objective tumor regression in the lung metastases. The clinical benefit rate (complete response + partial response + stable disease > 6 months) was 9%, median progression-free survival was 7 weeks (95% confidence interval [CI], 7-19), and median overall survival was 46 weeks (95% CI, 27-not applicable). Conclusion The study did not meet the prespecified criteria for ORR in the first stage of the Simon 2-stage model in this heavily pretreated unselected population of MBC. However, activity was observed in trastuzumab-refractory HER2-positive and TNBC. Ganetespib was well tolerated and responses in more targeted populations harboring specific HSP90-dependent oncoproteins justifies its further study, particularly as part of rational combinations.

Original languageEnglish
Pages (from-to)154-160
Number of pages7
JournalClinical Breast Cancer
Volume14
Issue number3
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • Breast cancer
  • Ganetespib
  • HER2
  • HSP90
  • Monotherapy

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