S Ramalingam1, G Goss2, R Rosell3, G Schmid-Bindert4, B Zaric5, Z Andric6, I Bondarenko7, D Komov8, T Ceric9, F Khuri10, M Samarzija11, E Felip12, T Ciuleanu13, V Hirsh14, T Wehler15, J Spicer16, R Salgia17, G Shapiro18, E Sheldon19, F Teofilovici19, V Vukovic19, D Fennell20. 1. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, USA ssramal@emory.edu. 2. Division of Medical Oncology, University of Ottawa, Ottawa, Canada. 3. Medical Oncology Service, Catalan Institute of Oncology, Badalona, Spain. 4. Department of Surgery, University Medical Center Mannheim, Mannheim, Germany. 5. Institute for Pulmonary Diseases of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad. 6. Clinic for Oncology, Medical Center Bezanijska Kosa, Belgrade, Serbia. 7. Department of Oncology, Multiple-Discipline Clinical Hospital #4, Dnipropetrovsk, Ukraine. 8. Surgical Department of Tumor Diagnostics, Russian Academy of Medical Science, Moscow, Russia. 9. Oncology Clinic, University of Sarajevo Clinics Center, Sarajevo, Bosnia. 10. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, USA. 11. Department for Respiratory Diseases Jordanovac, University of Zagreb, Zagreb, Croatia. 12. Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. 13. Department of Medical Oncology, Oncological Institute Ion Chiricuta, Cluj-Napoca, Romania. 14. Department of Medical Oncology, McGill University Health Centre, Montreal, Canada. 15. Third Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Mainz, Germany. 16. Department of Research Oncology, King's College London, London, UK. 17. Department of Medicine, University of Chicago, Chicago. 18. Department of Medical Oncology, Dana Farber Cancer Institute, Boston. 19. Department of Clinical Research, Synta Pharmaceuticals Corp., Lexington, USA. 20. Department of Cancer Studies, University of Leicester, Leicester, UK.
Abstract
BACKGROUND: This trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely to benefit from the combination. PATIENTS AND METHODS: Patients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m(2) on day 1) was administered alone or with ganetespib (150 mg/m(2) on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS). RESULTS: Of 385 patients enrolled, 381 were treated. Early in the trial, increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma histology were subsequently enrolled. Neutropenia was the most common grade ≥3 adverse event: 41% in the combination arm versus 42% in docetaxel alone. There was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P = 0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P = 0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease >6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS (adjusted HR = 0.69, P = 0.0191). CONCLUSION:Advanced lung adenocarcinoma patients treated withganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients >6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.
RCT Entities:
BACKGROUND: This trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely to benefit from the combination. PATIENTS AND METHODS: Patients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m(2) on day 1) was administered alone or with ganetespib (150 mg/m(2) on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS). RESULTS: Of 385 patients enrolled, 381 were treated. Early in the trial, increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma histology were subsequently enrolled. Neutropenia was the most common grade ≥3 adverse event: 41% in the combination arm versus 42% in docetaxel alone. There was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P = 0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P = 0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinomapatients diagnosed with advanced disease >6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS (adjusted HR = 0.69, P = 0.0191). CONCLUSION: Advanced lung adenocarcinomapatients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients >6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.
Authors: Yifan Wang; Hui Liu; Lixia Diao; Adam Potter; Jianhu Zhang; Yawei Qiao; Jing Wang; David A Proia; Ramesh Tailor; Ritsuko Komaki; Steven H Lin Journal: Clin Cancer Res Date: 2016-06-28 Impact factor: 12.531
Authors: Roland Walter; Kuan-Ting Pan; Carmen Doebele; Federico Comoglio; Katarzyna Tomska; Hanibal Bohnenberger; Ryan M Young; Laura Jacobs; Ulrich Keller; Halvard Bönig; Michael Engelke; Andreas Rosenwald; Henning Urlaub; Louis M Staudt; Hubert Serve; Thorsten Zenz; Thomas Oellerich Journal: Blood Date: 2016-11-15 Impact factor: 22.113