Rathi N Pillai1, Dean A Fennell2, Vladimir Kovcin3, Tudor-Eliade Ciuleanu4, Rodryg Ramlau5, Dariusz Kowalski6, Michael Schenker7, Ilker Yalcin8, Florentina Teofilovici8, Vojo M Vukovic8, Suresh S Ramalingam1. 1. Winship Cancer Institute, Emory University, Atlanta, GA. 2. University of Leicester, Leicester, United Kingdom. 3. Clinical Hospital Centre Bežanijska Beograd, Belgrade, Serbia. 4. Prof Dr Ion Chiricuţă Institute of Oncology and Universitatea de Medicină şi Farmacie Iuliu Hatiegan, Cluj-Napoca, Romania. 5. Poznan University of Medical Sciences, Poznan, Poland. 6. Medical University of Warsaw, Warsaw, Poland. 7. University of Medicine and Pharmacy Craiova, Craiova, Romania. 8. Synta Pharmaceuticals, West Conshohocken, PA.
Abstract
PURPOSE:Ganetespib, a highly potent heat shock protein 90 inhibitor, blocks multiple oncogenic pathways, resulting in antitumor activity. We evaluated the combination of ganetespib and docetaxel for second-line therapy of patients with advanced adenocarcinoma of the lung. PATIENTS AND METHODS: In this international phase III trial, patients with stage IIIB or IV adenocarcinoma diagnosed > 6 months before study entry and 1 prior systemic therapy were randomly assigned (1:1) to ganetespib 150 mg/m2 on days 1 and 15 with docetaxel 75 mg/m2 on day 1 of a 21-day cycle or to docetaxel alone. The primary end point was overall survival (OS). RESULTS: Of 677 enrolled patients, 335 were randomly assigned toganetespib and docetaxel and 337 were assigned to docetaxel. The trial was stopped early as a result of futility at a planned interim analysis. The median OS time was 10.9 months (95% CI, 9.0 to 12.3 months) in the ganetespib and docetaxel arm compared with 10.5 months (95% CI, 8.6 to 12.2 months) in docetaxel arm (hazard ratio [HR], 1.11; 95% CI, 0.899 to 1.372; P = .329). Median progression-free survival was 4.2 months in the ganetespib and docetaxel arm and 4.3 months in the docetaxel arm (HR, 1.16; 95% CI, 0.96 to 1.403; P = .119). The addition of ganetespib did not improve outcomes compared with docetaxel alone for any secondary end point, including survival in the elevated lactate dehydrogenase or EGFR and ALK wild-type populations. The most common grade 3 or 4 adverse event in both arms was neutropenia (30.9% with ganetespib and docetaxel v 25% with docetaxel). CONCLUSION: The addition of ganetespib to docetaxel did not result in improved survival for salvage therapy of patients with advanced-stage lung adenocarcinoma.
RCT Entities:
PURPOSE:Ganetespib, a highly potent heat shock protein 90 inhibitor, blocks multiple oncogenic pathways, resulting in antitumor activity. We evaluated the combination of ganetespib and docetaxel for second-line therapy of patients with advanced adenocarcinoma of the lung. PATIENTS AND METHODS: In this international phase III trial, patients with stage IIIB or IV adenocarcinoma diagnosed > 6 months before study entry and 1 prior systemic therapy were randomly assigned (1:1) to ganetespib 150 mg/m2 on days 1 and 15 with docetaxel 75 mg/m2 on day 1 of a 21-day cycle or to docetaxel alone. The primary end point was overall survival (OS). RESULTS: Of 677 enrolled patients, 335 were randomly assigned to ganetespib and docetaxel and 337 were assigned to docetaxel. The trial was stopped early as a result of futility at a planned interim analysis. The median OS time was 10.9 months (95% CI, 9.0 to 12.3 months) in the ganetespib and docetaxel arm compared with 10.5 months (95% CI, 8.6 to 12.2 months) in docetaxel arm (hazard ratio [HR], 1.11; 95% CI, 0.899 to 1.372; P = .329). Median progression-free survival was 4.2 months in the ganetespib and docetaxel arm and 4.3 months in the docetaxel arm (HR, 1.16; 95% CI, 0.96 to 1.403; P = .119). The addition of ganetespib did not improve outcomes compared with docetaxel alone for any secondary end point, including survival in the elevated lactate dehydrogenase or EGFR and ALK wild-type populations. The most common grade 3 or 4 adverse event in both arms was neutropenia (30.9% with ganetespib and docetaxel v 25% with docetaxel). CONCLUSION: The addition of ganetespib to docetaxel did not result in improved survival for salvage therapy of patients with advanced-stage lung adenocarcinoma.
Authors: Xiaoqian Li; Xuesong Tong; Bin Liu; Zeng Li; Jing Ding; Jiang Li; Min Zheng; Yuke Tian; Siyou Yan; Meiling Huang; Jun Ge Journal: J Int Med Res Date: 2021-12 Impact factor: 1.671