A phase II open-label study of ganetespib, a novel heat shock protein 90 inhibitor for patients with metastatic breast cancer.
Publication/Presentation Date
6-1-2014
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/m(2) 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.
Volume
14
Issue
3
First Page
154
Last Page
160
ISSN
1938-0666
Published In/Presented At
Jhaveri, K., Chandarlapaty, S., Lake, D., Gilewski, T., Robson, M., Goldfarb, S., Drullinsky, P., Sugarman, S., Wasserheit-Leiblich, C., Fasano, J., Moynahan, M. E., D'Andrea, G., Lim, K., Reddington, L., Haque, S., Patil, S., Bauman, L., Vukovic, V., El-Hariry, I., Hudis, C., … Modi, S. (2014). A phase II open-label study of ganetespib, a novel heat shock protein 90 inhibitor for patients with metastatic breast cancer. Clinical breast cancer, 14(3), 154–160. https://doi.org/10.1016/j.clbc.2013.12.012
Disciplines
Medicine and Health Sciences
PubMedID
24512858
Department(s)
Department of Medicine
Document Type
Article