Apatinib for Advanced Osteosarcoma After Failure of Standard Multimodal Therapy

Summary

After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades.Thus, the investigators explored apatinib activity in patients with relapsed and unresectable osteosarcoma after the failure of first-line or second-line chemotherapy. Patients \>16 years, progressing after standard treatment, were eligible to receive 500 mg or 750 mg of apatinib once daily until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) at 4 months and objective response rate (ORR). Secondary objectives were PFS, overall survival (OS), clinical benefit rate (CBR), defined as no progression at 6 months and safety.

Timeline

Start

2016-03

Primary completion

2017-12-30

Completion

2018-01-08

Publications

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• Background Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. doi: 10.1056/NEJMoa050753.
• Background Sleijfer S, Ray-Coquard I, Papai Z, Le Cesne A, Scurr M, Schoffski P, Collin F, Pandite L, Marreaud S, De Brauwer A, van Glabbeke M, Verweij J, Blay JY. 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). J Clin Oncol. 2009 Jul 1;27(19):3126-32. doi: 10.1200/JCO.2008.21.3223. Epub 2009 May 18.
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• Background Grignani G, Palmerini E, Dileo P, Asaftei SD, D'Ambrosio L, Pignochino Y, Mercuri M, Picci P, Fagioli F, Casali PG, Ferrari S, Aglietta M. A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study. Ann Oncol. 2012 Feb;23(2):508-16. doi: 10.1093/annonc/mdr151. Epub 2011 Apr 28.
• Background Yoo C, Lee J, Rha SY, Park KH, Kim TM, Kim YJ, Lee HJ, Lee KH, Ahn JH. Multicenter phase II study of everolimus in patients with metastatic or recurrent bone and soft-tissue sarcomas after failure of anthracycline and ifosfamide. Invest New Drugs. 2013 Dec;31(6):1602-8. doi: 10.1007/s10637-013-0028-7. Epub 2013 Sep 14.
• Background Grignani G, Palmerini E, Ferraresi V, D'Ambrosio L, Bertulli R, Asaftei SD, Tamburini A, Pignochino Y, Sangiolo D, Marchesi E, Capozzi F, Biagini R, Gambarotti M, Fagioli F, Casali PG, Picci P, Ferrari S, Aglietta M; Italian Sarcoma Group. Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial. Lancet Oncol. 2015 Jan;16(1):98-107. doi: 10.1016/S1470-2045(14)71136-2. Epub 2014 Dec 11.
• Background Lammli J, Fan M, Rosenthal HG, Patni M, Rinehart E, Vergara G, Ablah E, Wooley PH, Lucas G, Yang SY. Expression of Vascular Endothelial Growth Factor correlates with the advance of clinical osteosarcoma. Int Orthop. 2012 Nov;36(11):2307-13. doi: 10.1007/s00264-012-1629-z. Epub 2012 Aug 2.
• Background Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5.
• Background Aras M, Erdil TY, Dane F, Gungor S, Ones T, Dede F, Inanir S, Turoglu HT. Comparison of WHO, RECIST 1.1, EORTC, and PERCIST criteria in the evaluation of treatment response in malignant solid tumors. Nucl Med Commun. 2016 Jan;37(1):9-15. doi: 10.1097/MNM.0000000000000401.
• Background Semiglazov V. RECIST for Response (Clinical and Imaging) in Neoadjuvant Clinical Trials in Operable Breast Cancer. J Natl Cancer Inst Monogr. 2015 May;2015(51):21-3. doi: 10.1093/jncimonographs/lgv021.
• Background Young J, Badgery-Parker T, Dobbins T, Jorgensen M, Gibbs P, Faragher I, Jones I, Currow D. Comparison of ECOG/WHO performance status and ASA score as a measure of functional status. J Pain Symptom Manage. 2015 Feb;49(2):258-64. doi: 10.1016/j.jpainsymman.2014.06.006. Epub 2014 Jul 1.
• Background Broderick JM, Hussey J, Kennedy MJ, O' Donnell DM. Patients over 65 years are assigned lower ECOG PS scores than younger patients, although objectively measured physical activity is no different. J Geriatr Oncol. 2014 Jan;5(1):49-56. doi: 10.1016/j.jgo.2013.07.010. Epub 2013 Sep 5.

Drugs

Indications