Journal ArticleDOI
Pazopanib, a Multikinase Angiogenesis Inhibitor, in Patients With Relapsed or Refractory Advanced Soft Tissue Sarcoma: A Phase II Study From the European Organisation for Research and Treatment of Cancer―Soft Tissue and Bone Sarcoma Group (EORTC Study 62043)
Stefan Sleijfer,Isabelle Ray-Coquard,Zsuzsa Papai,Axel Le Cesne,Michelle Scurr,Patrick Schöffski,F. Collin,Lini Pandite,Sandrine Marreaud,Annick De Brauwer,Martine Van Glabbeke,Jaap Verweij,Jean-Yves Blay +12 more
TLDR
Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patientswith leiomyosarcoma, synovial sarcomas, and other STS types.Abstract:
PURPOSE Given the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS. PATIENTS AND METHODS Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR(12 weeks)). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; alpha = beta = .1) for each stratum. Results One hundred forty-two patients were enrolled. The adipocytic STS stratum was closed after the first stage, given insufficient activity (PFR(12 weeks), five [26%] of19). PFR(12 weeks) was 18 (44%) of 41 patients in the leiomyosarcoma cohort, 18 (49%) of 37 in the synovial sarcomas, and 16 (39%) of 41 in the other STS types. Compared with historical controls who were treated with second-line chemotherapy, progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached. The most frequent drug-related toxicities were hypertension, fatigue, hypopigmentation, and nausea. Other toxicities included liver enzyme elevations, myelosuppression, and proteinuria, all of which were mostly grades 1 to 2. The most frequent grades 3 to 4 toxicities were hyperbilirubinemia (6.3%), hypertension (7.7%), and fatigue (7.7%). CONCLUSION Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas, synovial sarcomas, and other STS types.read more
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Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial
Winette T. A. van der Graaf,Jean-Yves Blay,Sant P. Chawla,Dong Wan Kim,B. Bui-Nguyen,Paolo G. Casali,Patrick Schöffski,Massimo Aglietta,Arthur P. Staddon,Yasuo Beppu,Axel Le Cesne,Hans Gelderblom,Ian Judson,Nobuhito Araki,M. Ouali,Sandrine Marreaud,Rachel Hodge,Mohammed R. Dewji,Corneel Coens,George D. Demetri,Christopher D.M. Fletcher,Angelo Paolo Dei Tos,Peter Hohenberger +22 more
TL;DR: This phase 3 study investigated the effect of pazopanib on progression-free survival in patients with metastatic non-adipocytic soft-tissue sarcoma after failure of standard chemotherapy.
Journal ArticleDOI
Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial
George D. Demetri,Margaret von Mehren,Robin L. Jones,Martee L. Hensley,Scott M. Schuetze,Arthur P. Staddon,Mohammed M. Milhem,Anthony D. Elias,Kristen N. Ganjoo,Hussein Tawbi,Brian A. Van Tine,Alexander I. Spira,Andrew Dean,Nushmia Z. Khokhar,Youn C. Park,Roland Elmar Knoblauch,Trilok V. Parekh,Robert G. Maki,Shreyaskumar Patel +18 more
TL;DR: Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies.
Journal ArticleDOI
Advances in sarcoma genomics and new therapeutic targets
Barry S. Taylor,Jordi Barretina,Jordi Barretina,Robert G. Maki,Cristina R. Antonescu,Samuel Singer,Marc Ladanyi +6 more
TL;DR: The core molecular determinants of sarcomagenesis are discussed and the emerging genomic and functional genetic approaches that, coupled with novel therapeutic strategies, have the potential to transform the care of patients with sarcoma are emphasized.
Journal ArticleDOI
Anti-angiogenesis therapy in cancer: Current challenges and future perspectives
TL;DR: It has been nearly 9years since the first anti-angiogenic drug was approved for treatment of metastatic colorectal cancer and continued clinical and preclinical investigations have identified major drawbacks associated with the application of this class of agents, including inherent/acquired resistance and induction of tumor invasiveness.
Journal ArticleDOI
A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study
Giovanni Grignani,Emanuela Palmerini,Palma Dileo,Sebastian Dorin Asaftei,Lorenzo D'Ambrosio,Ymera Pignochino,Mario Mercuri,Piero Picci,Franca Fagioli,Paolo G. Casali,Stefano Ferrari,Massimo Aglietta +11 more
TL;DR: Sorafenib demonstrated activity as a second- or third-line treatment in terms of progression-free survival at 4 months with some unprecedented long-lasting responses, and deserves further investigations.
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Robert G. Maki,J. Kyle Wathen,Shreyaskumar Patel,Dennis A. Priebat,Scott H. Okuno,Brian L. Samuels,Michael P. Fanucchi,David C. Harmon,Scott M. Schuetze,Denise Reinke,Peter F. Thall,Robert S. Benjamin,Laurence H. Baker,Martee L. Hensley +13 more
TL;DR: Gem citabine as a single agent and the combination of gemcitabine and docetaxel have activity in patients with metastatic soft tissue sarcoma are found to have activity.
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