@article{ac5959eb1c9d41879ba1b4ad562eea40,
title = "A phase II study of pazopanib as front-line therapy in patients with non-resectable or metastatic soft-tissue sarcomas who are not candidates for chemotherapy",
abstract = "Background: Cytotoxic chemotherapy remains the standard of care first-line treatment for advanced and metastatic soft-tissue sarcomas (STSs). Certain patients may not be chemotherapy candidates based upon age or co-morbidities, leaving limited treatment options. Pazopanib is a multi-targeted tyrosine kinase inhibitor that is FDA-approved for metastatic STS after the first line. We proposed a phase II study evaluating pazopanib as a first-line agent in patients with advanced disease who are deemed not to be candidates for chemotherapy. Methods: Eligible patients were at least 18 years old, not candidates for chemotherapyand were treatment naive. Pazopanib was titrated from 200 mg twice daily to a goal of 800 mg daily. The primary end point was the clinical benefit rate (CBR) (CBR = completed response + partial response + stable disease per Response Evaluation Criteria in Solid Tumours [RECIST 1.1]) at 16 weeks. The sample size of 56 evaluable patients was calculated to provide 80% power to test a hypothesised CBR of ≥35% against an unfavourable CBR of ≤20%. If ≥ 17 patients achieved benefit, the null CBR of 20% would be rejected at a nominal 5% alpha level. Secondary end points included progression-free survival (PFS), overall survival (OS), quality of life and serum biomarkers. Findings: Fifty-six patients were enrolled from May 2015 to February 2019 and are included in the intention-to-treat analysis. Median PFS was 3.67 (2.62–7.25) months. Median OS was 14.16 (95% confidence interval [CI]: 8.4-NR) months, CBR = 39.29% (22/56) (CI = 0.265–0.533, p = 0.0007). No new or unexpected adverse events were seen. The most common grade I–II events were diarrhoea, nausea and fatigue. The most common grade III–IV events were hypertension and liver function test abnormalities. Interpretation: These data suggest that there is a benefit to front-line pazopanib in patients with STS who are not candidates for cytotoxic chemotherapy.",
keywords = "Clinical benefit rate, Elderly, Elderly patients, Pazopanib, Phase II, Sarcoma, Soft-tissue sarcoma",
author = "Hirbe, {Angela C.} and Vanessa Eulo and Moon, {Chang I.} and Jingqin Luo and Stephanie Myles and Mahesh Seetharam and Jacqui Toeniskoetter and Tammy Kershner and Sasha Haarberg and Mark Agulnik and Varun Monga and Mohammad Milhem and Amanda Parkes and Steven Robinson and Scott Okuno and Steven Attia and {Van Tine}, {Brian A.}",
note = "Funding Information: This study was funded by Novartis . The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: M.A. reports receiving consultation fees from Novartis, Lilly, Immune Design, Bayer; Speaker Bureau: Janssen, Eisai, BMS, Bayer. V.M. reports receiving travel funding from Deciphera; has received research funding from Immunocellular and Orbus Therapeutics . M.M. reports being a member of the consultant/advisory boards with Amgen, Trieza, Biontech, Blueprint Medicine, Immunocore, Array BioPharma, INC. S.R. reports receiving research support from TRACON Pharmaceutical; has been a member of the advisory boards with BTG International and the Society of Interventional Radiology Foundation; has received honoraria to institution; all outside the submitted work. S.A. has received research funding from Desmoid Tumor Research Foundation ; has also received research funding to Institution from AB Science , TRACON Pharma , CytRx Corporation , Bayer , Novartis , Daiichi Sankyo , Lilly , Immune Design , Karyopharm Therapeutics , Epizyme , Blueprint Medicines , Genmab , CBA Pharma , Merck , Philogen , Gradalis , Deciphera , Takeda , Incyte , Springworks , Adaptimmune , Advenchen Laboratories , Bavarian Nordic , BTG , PTC Therapeutics , GlaxoSmithKline , FORMA Therapeutics ; has received travel fees, accommodation expenses and general expenses from Immune Design. B.V.T. has received Basic Science Grant Funding from Pfizer , Tracon and Merck ; has received consulting fees from Epizyme, Lilly, CytRx, Janssen, Immune Design, Daiichi Sankyo, Plexxikon and Adaptimmune; has received speaking fees from Caris, Janseen and Lilly; and has received travel support from Adaptimmune and Lilly. All the authors have no conflict of interests to disclose. Funding Information: This study was funded by Novartis. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.M.A. reports receiving consultation fees from Novartis, Lilly, Immune Design, Bayer; Speaker Bureau: Janssen, Eisai, BMS, Bayer. V.M. reports receiving travel funding from Deciphera; has received research funding from Immunocellular and Orbus Therapeutics. M.M. reports being a member of the consultant/advisory boards with Amgen, Trieza, Biontech, Blueprint Medicine, Immunocore, Array BioPharma, INC. S.R. reports receiving research support from TRACON Pharmaceutical; has been a member of the advisory boards with BTG International and the Society of Interventional Radiology Foundation; has received honoraria to institution; all outside the submitted work. S.A. has received research funding from Desmoid Tumor Research Foundation; has also received research funding to Institution from AB Science, TRACON Pharma, CytRx Corporation, Bayer, Novartis, Daiichi Sankyo, Lilly, Immune Design, Karyopharm Therapeutics, Epizyme, Blueprint Medicines, Genmab, CBA Pharma, Merck, Philogen, Gradalis, Deciphera, Takeda, Incyte, Springworks, Adaptimmune, Advenchen Laboratories, Bavarian Nordic, BTG, PTC Therapeutics, GlaxoSmithKline, FORMA Therapeutics; has received travel fees, accommodation expenses and general expenses from Immune Design. B.V.T. has received Basic Science Grant Funding from Pfizer, Tracon and Merck; has received consulting fees from Epizyme, Lilly, CytRx, Janssen, Immune Design, Daiichi Sankyo, Plexxikon and Adaptimmune; has received speaking fees from Caris, Janseen and Lilly; and has received travel support from Adaptimmune and Lilly. All the authors have no conflict of interests to disclose. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = sep,
doi = "10.1016/j.ejca.2020.06.016",
language = "English (US)",
volume = "137",
pages = "1--9",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
}