A phase II open-label study of ganetespib, a novel heat shock protein 90 inhibitor for patients with Metastatic breast cancer Journal Article
| Authors: | 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. |
| Article Title: | A phase II open-label study of ganetespib, a novel heat shock protein 90 inhibitor for patients with Metastatic breast cancer |
| 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. © 2014 Elsevier Inc. All rights reserved. |
| Keywords: | monotherapy; breast cancer; her2; hsp90; ganetespib |
| Journal Title: | Clinical Breast Cancer |
| Volume: | 14 |
| Issue: | 3 |
| ISSN: | 1526-8209 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2014-06-01 |
| Start Page: | 154 |
| End Page: | 160 |
| Language: | English |
| DOI: | 10.1016/j.clbc.2013.12.012 |
| PROVIDER: | scopus |
| PUBMED: | 24512858 |
| DOI/URL: | |
| Notes: | Clin. Breast Cancer -- Export Date: 2 June 2014 -- CODEN: CBCLB -- Source: Scopus |
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