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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Komal
authors: K
authors: Jhaveri
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Sarat
authors: S
authors: Chandarlapaty
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Diana
authors: D
authors: Lake
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Teresa
authors: T
authors: Gilewski
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Mark
authors: M
authors: Robson
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Shari
authors: S
authors: Goldfarb
authors: Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Pamela
authors: P
authors: Drullinsky
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Steven
authors: S
authors: Sugarman
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Carolyn
authors: C
authors: Wasserheit-Leiblich
authors: Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Julie
authors: J
authors: Fasano
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Mary Ellen
authors: ME
authors: Moynahan
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Gabriella
authors: G
authors: D'Andrea
authors: Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Kristina
authors: K
authors: Lim
authors: Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Laura
authors: L
authors: Reddington
authors: Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Sofia
authors: S
authors: Haque
authors: Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Sujata
authors: S
authors: Patil
authors: Synta Pharmaceuticals Inc, Lexington, MA.
authors: Lynne
authors: L
authors: Bauman
authors: Synta Pharmaceuticals Inc, Lexington, MA.
authors: Vojo
authors: V
authors: Vukovic
authors: Synta Pharmaceuticals Inc, Lexington, MA.
authors: Iman
authors: I
authors: El-Hariry
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College.
authors: Clifford
authors: C
authors: Hudis
authors: Memorial Sloan-Kettering Cancer Center, New York, NY; Weil Cornell Medical College. Electronic address: modis@mskcc.org.
authors: Shanu
authors: S
authors: Modi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; C533237:STA 9090; D014230:Triazoles
keywords: Breast cancer; Ganetespib; HER2; HSP90; Monotherapy