A randomized study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel versus docetaxel alone for second-line therapy of lung adenocarcinoma (GALAXY-1).

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Oral Abstract Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr CRA8007)
Suresh S. Ramalingam, Glenwood D. Goss, Zoran Gojko Andric, Igor Bondarenko, Bojan Zaric, Timur Ceric, Elena Vladimir Poddubskaya, Tudor-Eliade Ciuleanu, James F. Spicer, Enriqueta Felip, Vera Hirsh, Christian Manegold, Rafael Rosell, Fadlo Raja Khuri, Vojislav M. Vukovic, Florentina Teofilovici, Iman El-Hariry, Wei Guo, Safi R. Bahcall, Dean Fennell; The Winship Cancer Institute of Emory University, Atlanta, GA; The Ottawa Hospital Cancer Center, Ottawa, ON, Canada; Clinical Hospital Centre Bezanijska Kosa, Beograd, Serbia; Municipal Institution Dnipropetrov, Dnipropetrovsk, Ukraine; University of Novi Sad, Institute for Pulmonary Diseases of Vojvodina, Novi Sad, Serbia; Clinical Center University of Sarajevo, Sarajevo, Bosnia; Unit of Russian Academy of Medical Sciences, Moscow, Russia; Prof. Dr. Ion Chiricuta Institute of Oncology, Department of Medical Oncology, Cluj-Napoca, Romania; King’s College London, Guy’s Hospital, London, United Kingdom; Thoracic Tumors Group, Vall d’Hebron Institute of Oncology, Barcelona, Spain; McGill University Health Centre, Montreal, QC, Canada; University Medical Center, Mannheim, Germany; Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Pangaea Biotech, Cancer Therapeutics Innovation Group, USP Institut Universitari Dexeus, Barcelona, Spain; Synta Pharmaceuticals, Inc., Lexington, MA; University of Leicester, Leicester, United Kingdom

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Heat shock protein 90 chaperone function is critical for the biological effects of several oncoproteins. Ganetespib (G) is a highly potent 2nd-generation Hsp90 inhibitor with a favorable safety profile and single-agent clinical activity. Methods: Based on synergistic preclinical interactions between docetaxel (D) and G, we conducted a randomized (1:1), international open-label study of D with or without G. Patients with advanced lung adenocarcinoma, one prior systemic therapy, and ECOG PS 0/1 were included. D was given at 75 mg/m2 on day 1 of a three-week cycle. In the experimental arm, D was given on day 1 and G at 150 mg/m2 on days 1 and 15. The co-primary endpoints were PFS in patients with elevated LDH (eLDH) levels, or tumors harboring KRAS mutations. Key secondary endpoints were OS and PFS in all adenocarcinoma patients. Target enrollment was 240 adenocarcinoma, 120 eLDH, and 80 mKRAS patients. Statistical tests are 1-sided. Results: Enrollment of 255 adenocarcinoma patients completed in November 2012; results are reported for this population. Patient characteristics were balanced (median age 60 years, males ~60%, PS 0 ~40% and never-smoker ~25%). For D+G vs. D the median number of cycles delivered was 5 vs. 4; the grade 3/4 adverse events were neutropenia 38% vs. 37%; fatigue 4% vs. 3%; anemia 7% vs. 6%; diarrhea 3% vs. 0; fever with neutropenia 8% vs. 2%. At the time of abstract submission OS HR was 0.69 (90% CI 0.48 to 0.99, p=0.093), the PFS HR was 0.70 (90% CI 0.53 to 0.94, p=0.012), and the ORR was 15% vs 11%, favoring D+G. For patients that were enrolled >6 months after diagnosis of advanced NSCLC (N=175; 69%), a prespecified stratification factor, the OS HR was 0.41 (90% CI 0.25 to 0.67, p=0.0009), the PFS HR was 0.47 (90% CI 0.32 to 0.69, p=0.0005), and the ORR was 16% vs 12%. Updated results for both populations above, as well as for the eLDH and mKRAS subsets, will be presented. Conclusions: D+G demonstrated improvement in OS, PFS, and ORR over D alone for second-line therapy of lung adenocarcinoma. A phase III study in second-line advanced adenocarcinoma patients (> 6 months from diagnosis) is ongoing (GALAXY-2). Clinical trial information: NCT01348126.