A Phase 2 Study of the Hsp90 Inhibitor AUY922 as Treatment for Patients with Refractory Gastrointestinal Stromal Tumors

Cancer Investigation

Volumn 34, Issue 6, 2016, Pages 265-270

  Bendell, Johanna C ^a,b   Bauer, Todd M ^a,b   Lamar, Ruth ^a,b   Joseph, Mathew ^a,b   Penley, William ^a,b   Thompson, Dana S ^a,b   Spigel, David R ^a,b   Owera, Rami ^c   Lane, Cassie M ^a   Earwood, Chris ^a   Burris, Howard A ^a,b  

^a SARAH CANNON RESEARCH INSTITUTE   (United States)

^b PLLC   (United States)

^c Woodlands Medical Specialists   (United States)

Author keywords

AUY922; GIST; Heat shock protein 90; Hsp90

Indexed keywords

ALKALINE PHOSPHATASE; ANTINEOPLASTIC AGENT; IMATINIB; LUMINESPIB; SUNITINIB; 5-(2,4-DIHYDROXY-5-ISOPROPYLPHENYL)-4-(4-MORPHOLIN-4-YLMETHYLPHENYL)ISOXAZOLE-3-CARBOXYLIC ACID ETHYLAMIDE; HEAT SHOCK PROTEIN 90; ISOXAZOLE DERIVATIVE; RESORCINOL DERIVATIVE;

ABDOMINAL PAIN; ADULT; ALKALINE PHOSPHATASE BLOOD LEVEL; ANEMIA; ANOREXIA; ARTICLE; ASTHENIA; BLURRED VISION; CLINICAL ARTICLE; CONSTIPATION; CONTINUOUS INFUSION; DARK ADAPTATION; DEHYDRATION; DIARRHEA; DISEASE COURSE; DRUG DEGRADATION; DRUG DOSE REDUCTION; DRUG SAFETY; DYSGEUSIA; EYE TOXICITY; FATIGUE; FEMALE; GASTROINTESTINAL STROMAL TUMOR; HEADACHE; HUMAN; LEUKOPENIA; LIGHT ADAPTATION; MALE; MIDDLE AGED; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NIGHT BLINDNESS; OVERALL SURVIVAL; PAIN; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; QTC INTERVAL; REFRACTORY GASTROINTESTINAL STROMAL TUMOR; SIDE EFFECT; THROMBOCYTOPENIA; TREATMENT RESPONSE; TUMOR GROWTH; VOMITING; AGED; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DRUG RESISTANCE; FOLLOW UP; GASTROINTESTINAL STROMAL TUMORS; GENETICS; MORTALITY; MULTIMODALITY CANCER THERAPY; MUTATION; PATHOLOGY; RETREATMENT; TREATMENT OUTCOME; YOUNG ADULT;

ADULT; AGED; ANTINEOPLASTIC AGENTS; COMBINED MODALITY THERAPY; DISEASE-FREE SURVIVAL; DRUG RESISTANCE, NEOPLASM; FEMALE; FOLLOW-UP STUDIES; GASTROINTESTINAL STROMAL TUMORS; HSP90 HEAT-SHOCK PROTEINS; HUMANS; ISOXAZOLES; MALE; MIDDLE AGED; MUTATION; RESORCINOLS; RETREATMENT; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84978612222     PISSN: 07357907     EISSN: 15324192     Source Type: Journal    
DOI: 10.1080/07357907.2016.1193746     Document Type: Article

References (18)

1. G.D.Demetri, von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw 2010;8(Suppl 2):S1–41; quiz S42–44.
2. H.Joensuu. Adjuvant treatment of GIST: patient selection and treatment strategies. Nat Rev Clin Oncol 2012;9(6):351–358.
3. G.D.Demetri, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347(7):472–480.
4. J.Verweij, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004;364(9440):1127–1134.
5. R.P.DeMatteo, Ballman KV, Antonescu CR, Corless C, Kolesnikova V, von Mehren M, et al. Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial. Ann Surg 2013;258(3):422–429.
6. C.R.Antonescu, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 2005;11(11):4182–4190.
7. M.V.Caram, S.M.Schuetze. Advanced or metastatic gastrointestinal stromal tumors: systemic treatment options. J Surg Oncol 2011;104(8):888–895.
8. G.D.Demetri, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006;368(9544):1329–1338.
9. G.Floris, Debiec-Rychter M, Wozniak A, Stefan C, Normant E, Faa G, et al. The heat shock protein 90 inhibitor IPI-504 induces KIT degradation, tumor shrinkage, and cell proliferation arrest in xenograft models of gastrointestinal stromal tumors. Mol Cancer Ther 2011;10(10):1897–1908.
10. S.Bauer, Yu LK, Demetri GD, Fletcher JA. Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor. Cancer Res 2006;66(18):9153–9161.
11. A.J.Wagner, Chugh R, Rosen LS, Morgan JA, George S, Gordon M, et al. A phase I study of the HSP90 inhibitor retaspimycin hydrochloride (IPI-504) in patients with gastrointestinal stromal tumors or soft-tissue sarcomas. Clin Cancer Res 2013;19(21):6020–6029.
12. C.Sessa, Shapiro GI, Bhalla KN, Britten C, Jacks KS, Mita M, et al. First-in-human phase I dose-escalation study of the HSP90 inhibitor AUY922 in patients with advanced solid tumors. Clin Cancer Res 2013;19(13):3671–3680.
13. E.Eisenhauer, Therasse P, Bogarts J, Schwartz L, Sargent D, Ford R, et al. New Response Evaluation Criteria in Solid Tumors: Revised RECIST Guideline (version 1.1). Eur J Cancer 2009;45:228–247.
14. E.Kaplan, P.Meier. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–481.
15. J.-Y.Blay, Molimard M, Cropet C, Domont J, Toulmonde M, Bompas E, et al. Final results of the multicenter randomized phase II PAZOGIST trial evaluating the efficacy of pazopanib (P) plus best supportive care (BSC) vs BSC alone in resistant unresectable metastatic and/or locally advanced gastrointestinal stromal tumors (GIST). ASCO Meeting Abstracts 2015;33(15_suppl):10506.
16. M.C.Heinrich, von Mehren M, Demetri GD, Fletcher JA, Sun JG, Kerstein D, et al. Ponatinib efficacy and safety in patients (pts) with advanced gastrointestinal stromal tumors (GIST) after tyrosine kinase inhibitor (TKI) failure: Results from a phase 2 study. ASCO Meeting Abstracts 2015;33(15_suppl):10535.
17. A.J.Wagner, Chugh R, Rosen LS, Morgan JA, George S, Gordon M, et al. A phase 1 study of the heat shock protein 90 inhibitor retaspimycin hydrochloride (IPI-504) in patients with gastrointestinal stromal tumors or soft tissue sarcomas. Clin Cancer Res 2013;19(21):6020–6029.
18. M.L.Johnson, Yu HA, Hart EM, Weitner BB, Rademaker AW, Patel JD, et al. Phase I/II Study of HSP90 Inhibitor AUY922 and Erlotinib for EGFR-Mutant Lung Cancer With Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. J Clin Oncol 2015;33(15):1666–1673.