Systemic treatment in advanced soft tissue sarcoma: what is standard, what is new

Anna Maria Frezza, Silvia Stacchiotti, Alessandro Gronchi, Anna Maria Frezza, Silvia Stacchiotti, Alessandro Gronchi

Abstract

For metastatic soft tissue sarcoma (STS) patients not eligible for surgery, systemic treatments, including standard chemotherapy and newer biological compounds, still play the most relevant role in the management of the disease. An anthracycline and alkylating agent combination has formed the cornerstone of chemotherapy in STS for more than 30 years, with its value over that of administration of anthracycline as a single agent still being debated. Efforts have been made to improve the activity and minimise the toxicity of the combination, as well as to explore the upfront efficacy of agents known to be active in sarcoma and to develop new biological compounds. Nevertheless, beyond the first line, evidence for medical treatment in STS is less robust and all the more driven by histology. Thus, the introduction of kinases and small molecule inhibitors in the treatment armamentarium for STS is a major achievement in this setting. Preliminary data on immunotherapy are also available and discussed in this review.

Keywords: Advanced sarcoma; Chemotherapy; Immunotherapy; Metastatic sarcoma; Sarcoma; Survival; Tyrosine kinase inhibitors; VEGF inhibitors.

References

    1. Fletcher CD, Hogendoorn PC, Mertens F, Bridge J. WHO Classification of Tumours of Soft Tissue and Bone. 4. Lyon: IARC press; 2013.
    1. Judson I, Verweij J, Gelderblom H, Hartmann JT, Schoffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15:415–23. doi: 10.1016/S1470-2045(14)70063-4.
    1. Ryan CW, Merimsky O, Agulnik M, Blay JY, Schuetze SM, Van Tine BA, Jones RL, Elias AD, Choy E, Alcindor T, et al. PICASSO III: A phase III, placebo-controlled study of doxorubicin with or without palifosfamide in patients with metastatic soft tissue sarcoma. J Clin Oncol. 2016;34:3898-3905.
    1. Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;388:488–97. doi: 10.1016/S0140-6736(16)30587-6.
    1. Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, et al. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007;25:3144–50. doi: 10.1200/JCO.2006.09.7717.
    1. Chawla SP, Papai Z, Mukhametshina G, Sankhala K, Vasylyev L, Fedenko A, Khamly K, Ganjoo K, Nagarkar R, Wieland S, Levitt DJ. First-line aldoxorubicin vs doxorubicin in metastatic or locally advanced unresectable soft-tissue sarcoma: a phase 2b randomized clinical trial. JAMA Oncol. 2015;1:1272–80. doi: 10.1001/jamaoncol.2015.3101.
    1. Salvatorelli E, Menna P, Gonzalez Paz O, Surapaneni S, Aukerman SL, Chello M, Covino E, Sung V, Minotti G. Pharmacokinetic characterization of amrubicin cardiac safety in an ex vivo human myocardial strip model. II. Amrubicin shows metabolic advantages over doxorubicin and epirubicin. J Pharmacol Exper Ther. 2012;341:474–83. doi: 10.1124/jpet.111.190264.
    1. Noguchi T, Ichii S, Morisada S, Yamaoka T, Yanagi Y. Tumor-selective distribution of an active metabolite of the 9-aminoanthracycline amrubicin. Jpn J Cancer Res. 1998;89:1061–6. doi: 10.1111/j.1349-7006.1998.tb00497.x.
    1. Gupta S, Gouw L, Wright J, Chawla S, Pitt D, Wade M, Boucher K, Sharma S. Phase II study of amrubicin (SM-5887), a synthetic 9-aminoanthracycline, as first line treatment in patients with metastatic or unresectable soft tissue sarcoma: durable response in myxoid liposarcoma with TLS-CHOP translocation. Invest New Drugs. 2016;34:243–52. doi: 10.1007/s10637-016-0333-z.
    1. Verschraegen CF, Chawla SP, Mita MM, Ryan CW, Blakely L, Keedy VL, Santoro A, Buck JY, Maki RG, Lewis JJ, PICASSO Study Investigators A phase II, randomized, controlled trial of palifosfamide plus doxorubicin versus doxorubicin in patients with soft tissue sarcoma (PICASSO) J Clin Oncol. 2010;28:15s. doi: 10.1200/jco.2010.28.15_suppl.10004.
    1. Tap W, Papai Z, van Tine B, Attia S, Ganjoo K, Jones RL, Schuetze S, Reed D, Chawla SP, Riedel R, Krarup-Hansen A, Italiano A, Hohenberger P, Grignani G, Cranmer L, Alcindor T, Lopez-Pousa A, Pearce T, Kroll S, Schoffski P. Randomized phase 3, multicenter, open-label study comparing evofosfamide (Evo) in combination with doxorubicin (D) vs. D alone in patients (pts) with advanced soft tissue sarcoma (STS): Study TH-CR-406/SARC021. Ann Oncol. 2016;27(Suppl_6):1395O. doi: 10.1093/annonc/mdw388.01.
    1. Seddon B, Whelan J, Strauss S, Leahy M, Woll P, Cowie F, Rothermundt C, Wood Z, Forsyth S, Khan I, et al. GeDDiS: A prospective randomised controlled phase III trial of gemcitabine and docetaxel compared with doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft tissue sarcomas (EudraCT 2009-014907-29). J Clin Oncol. 2015;33:(Suppl; abstr 10500).
    1. Bui-Nguyen B, Butrynski JE, Penel N, Blay JY, Isambert N, Milhem M, Kerst JM, Reyners AK, Litiere S, Marreaud S, et al. A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: the TRUSTS trial. Eur J Cancer. 2015;51:1312–20. doi: 10.1016/j.ejca.2015.03.023.
    1. Martin-Broto J, Pousa AL, de Las PR, Garcia Del Muro X, Gutierrez A, Martinez-Trufero J, Cruz J, Alvarez R, Cubedo R, Redondo A, et al. Randomized phase II study of trabectedin and doxorubicin compared with doxorubicin alone as first-line treatment in patients with advanced soft tissue sarcomas: a Spanish group for research on sarcoma study. J Clin Oncol. 2016;34:2294–302. doi: 10.1200/JCO.2015.65.3329.
    1. Gelderblom H, Blay JY, Seddon BM, Leahy M, Ray-Coquard I, Sleijfer S, Kerst JM, Rutkowski P, Bauer S, Ouali M, et al. Brostallicin versus doxorubicin as first-line chemotherapy in patients with advanced or metastatic soft tissue sarcoma: an European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group randomised phase II and pharmacogenetic study. Eur J Cancer. 2014;50:388–96. doi: 10.1016/j.ejca.2013.10.002.
    1. Loizos N, Xu Y, Huber J, Liu M, Lu D, Finnerty B, Rolser R, Malikzay A, Persaud A, Corcoran E, et al. Targeting the platelet-derived growth factor receptor alpha with a neutralizing human monoclonal antibody inhibits the growth of tumor xenografts: implications as a potential therapeutic target. Mol Cancer Ther. 2005;4:369–79.
    1. Simon MP, Pedeutour F, Sirvent N, Grosgeorge J, Minoletti F, Coindre JM, Terrier-Lacombe MJ, Mandahl N, Craver RD, Blin N, et al. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nat Genet. 1997;15:95–8. doi: 10.1038/ng0197-95.
    1. Greco A, Fusetti L, Villa R, Sozzi G, Minoletti F, Mauri P, Pierotti MA. Transforming activity of the chimeric sequence formed by the fusion of collagen gene COL1A1 and the platelet derived growth factor b-chain gene in dermatofibrosarcoma protuberans. Oncogene. 1998;17:1313–9. doi: 10.1038/sj.onc.1202051.
    1. Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, et al. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol. 2010;28:1772–9. doi: 10.1200/JCO.2009.25.7899.
    1. Stacchiotti S, Pantaleo MA, Negri T, Astolfi A, Tazzari M, Dagrada GP, Urbini M, Indio V, Maestro R, Gronchi A, et al. Efficacy and biological activity of imatinib in metastatic dermatofibrosarcoma protuberans (DFSP) Clin Cancer Res. 2016;22:837–46. doi: 10.1158/1078-0432.CCR-15-1243.
    1. Reichardt P, Lindner T, Pink D, Thuss-Patience PC, Kretzschmar A, Dorken B. Chemotherapy in alveolar soft part sarcomas. What do we know? Eur J Cancer. 2003;39:1511–6. doi: 10.1016/S0959-8049(03)00264-8.
    1. Stacchiotti S, Libertini M, Negri T, Palassini E, Gronchi A, Fatigoni S, Poletti P, Vincenzi B, Dei Tos AP, Mariani L, et al. Response to chemotherapy of solitary fibrous tumour: a retrospective study. Eur J Cancer. 2013;49:2376–83. doi: 10.1016/j.ejca.2013.03.017.
    1. Stacchiotti S, Palassini E, Sanfilippo R, Vincenzi B, Arena MG, Bochicchio AM, De Rosa P, Nuzzo A, Turano S, Morosi C, et al. Gemcitabine in advanced angiosarcoma: a retrospective case series analysis from the Italian Rare Cancer Network. Ann Oncol. 2012;23:501–8. doi: 10.1093/annonc/mdr066.
    1. Duffaud F, Pautier P, Bui B, Hensley ML, Rey A, Penel N, Reinke D, Le Cesne A, Blay JY, Maki RG. A pooled analysis of the final results of the two randomized phase II studies comparing Gemcitabine (G) vs Gemcitabine + Docetaxel (G + D) in patients (pts) with metastatic/relapsed leiomyosarcoma (LMS) Milan: European Society for Medical Oncology; 2010.
    1. Maki RG, Wathen JK, Patel SR, Priebat DA, Okuno SH, Samuels B, Fanucchi M, Harmon DC, Schuetze SM, Reinke D, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected] J Clin Oncol. 2007;25:2755–63. doi: 10.1200/JCO.2006.10.4117.
    1. Dileo P, Morgan JA, Zahrieh D, Desai J, Salesi JM, Harmon DC, Quigley MT, Polson K, Demetri GD, George S. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007;109:1863–9. doi: 10.1002/cncr.22609.
    1. Garcia-Del-Muro X, Lopez-Pousa A, Maurel J, Martin J, Martinez-Trufero J, Casado A, Gomez-Espana A, Fra J, Cruz J, Poveda A, et al. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011;29:2528–33. doi: 10.1200/JCO.2010.33.6107.
    1. Stiles JM, Amaya C, Rains S, Diaz D, Pham R, Battiste J, Modiano JF, Kokta V, Boucheron LE, Mitchell DC, Bryan BA. Targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma. PLoS One. 2013;8 doi: 10.1371/journal.pone.0060021.
    1. Banavali S, Pasquier E, Andre N. Targeted therapy with propranolol and metronomic chemotherapy combination: sustained complete response of a relapsing metastatic angiosarcoma. Ecancermedicalscience. 2015;9:499. doi: 10.3332/ecancer.2015.499.
    1. Chow W, Amaya CN, Rains S, Chow M, Dickerson EB, Bryan BA. Growth attenuation of cutaneous angiosarcoma with propranolol-mediated beta-blockade. JAMA Dermatol. 2015;151:1226–9. doi: 10.1001/jamadermatol.2015.2554.
    1. Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S, Kerbrat P, Fournier C, Taieb S, Jimenez M, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clinical Oncol. 2008;26:5269–74. doi: 10.1200/JCO.2008.17.3146.
    1. Rosen G, Forscher C, Lowenbraun S, Eilber F, Eckardt J, Holmes C, Fu YS. Synovial sarcoma. Uniform response of metastases to high dose ifosfamide. Cancer. 1994;73:2506–11. doi: 10.1002/1097-0142(19940515)73:10<2506::AID-CNCR2820731009>;2-S.
    1. Spurrell EL, Fisher C, Thomas JM, Judson IR. Prognostic factors in advanced synovial sarcoma: an analysis of 104 patients treated at the Royal Marsden Hospital. Ann Oncol. 2005;16:437–44. doi: 10.1093/annonc/mdi082.
    1. Le Cesne A, Blay JY, Judson I, Van Oosterom A, Verweij J, Radford J, Lorigan P, Rodenhuis S, Ray-Coquard I, Bonvalot S, et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol. 2005;23:576–84. doi: 10.1200/JCO.2005.01.180.
    1. Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009;27:4188–96. doi: 10.1200/JCO.2008.21.0088.
    1. Forni C, Minuzzo M, Virdis E, Tamborini E, Simone M, Tavecchio M, Erba E, Grosso F, Gronchi A, Aman P, et al. Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Molec Cancer Therapeut. 2009;8:449–57. doi: 10.1158/1535-7163.MCT-08-0848.
    1. Grosso F, Jones RL, Demetri GD, Judson IR, Blay JY, Le Cesne A, Sanfilippo R, Casieri P, Collini P, Dileo P, et al. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol. 2007;8:595–602. doi: 10.1016/S1470-2045(07)70175-4.
    1. Dybdal-Hargreaves NF, Risinger AL, Mooberry SL. Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent. Clin Cancer Res. 2015;21:2445–52. doi: 10.1158/1078-0432.CCR-14-3252.
    1. Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S, Uesugi M, Agoulnik S, Taylor N, Funahashi Y, Matsui J. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br J Cancer. 2014;110:1497–505. doi: 10.1038/bjc.2014.80.
    1. Schoffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016;387:1629–37. doi: 10.1016/S0140-6736(15)01283-0.
    1. Gronchi A, Miceli R, Colombo C, Collini P, Stacchiotti S, Olmi P, Mariani L, Bertulli R, Fiore M, Casali PG. Primary extremity soft tissue sarcomas: outcome improvement over time at a single institution. Ann Oncol. 2011;22:1675–81. doi: 10.1093/annonc/mdq643.
    1. Italiano A, Mathoulin-Pelissier S, Cesne AL, Terrier P, Bonvalot S, Collin F, Michels JJ, Blay JY, Coindre JM, Bui B. Trends in survival for patients with metastatic soft-tissue sarcoma. Cancer. 2011;117:1049–54. doi: 10.1002/cncr.25538.
    1. Savina M, Le Cesne A, Blay JY, Ray-Coquard I, Mir O, Toulmonde M, Cousin S, Terrier P, Ranchere-Vince D, Meeus P, Stoeckle E, Honoré C, Sargos P, Sunyach MP, Le Péchoux C, Giraud A, Bellera C, Le Loarer F, Italiano A. Patterns of care and outcomes of patients with METAstatic soft tissue SARComa ina real-life setting: the METASARC observational study. BMC Med. 2017;15:78. doi: 10.1186/s12916-017-0831-7.
    1. Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, Corless CL, Fletcher CD, Roberts PJ, Heinz D, et al. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol. 2008;26:620–5. doi: 10.1200/JCO.2007.13.4403.
    1. van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schoffski P, Aglietta M, Staddon AP, Beppu Y, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379:1879–86. doi: 10.1016/S0140-6736(12)60651-5.
    1. Sleijfer S, Ray-Coquard I, Papai Z, Le Cesne A, Scurr M, Schoffski P, Collin F, Pandite L, Marreaud S, De Brauwer A, et al. 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;27:3126–32. doi: 10.1200/JCO.2008.21.3223.
    1. Kollar A, Jones RL, Stacchiotti S, Gelderblom H, Guida M, Grignani G, Steeghs N, Safwat A, Katz D, Duffaud F, et al. Pazopanib in advanced vascular sarcomas: an EORTC Soft Tissue and Bone Sarcoma Group (STBSG) retrospective analysis. Acta Oncol. 2017;56:88–92. doi: 10.1080/0284186X.2016.1234068.
    1. Stacchiotti S, Tortoreto M, Baldi GG, Grignani G, Toss A, Badalamenti G, Cominetti D, Morosi C, Dei Tos AP, Festinese F, et al. Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour. Eur J Cancer. 2014;50:3021–8. doi: 10.1016/j.ejca.2014.09.004.
    1. Stacchiotti S, Mir O, Vincenzi B, Fedenko A, Maki R, Somaiah N, Brahmi M, Boye K, Hindi N, Paterczyk H, et al. Pazopanib (P) and trabectedin (T) in alveolar soft part sarcoma (ASPS). In: 2016 Connective Tissue Oncology Society Annual Meeting, Lisbon; 2016. p. 135. .
    1. Sarkissian S, Fruehauf J. Pazopanib and taxane combinations for metastatic or recurrent soft tissue sarcoma: A retrospective case series. J Clin Oncol. 2016;34:(suppl; abstr e22528).
    1. Schmoll H, Rüssel J, Reichardt P, Lindner L, Kopp H, Stein A, Cygon F, Heissner K. Pazopanib vs pazopanib + gemcitabine in refractory soft tissue sarcoma: A randomized phase II trial of the AIO. J Clin Oncol. 2016;34:(suppl; abstr 11004).
    1. Attia S, Kumar Sankhala K, Riedel R, Robinson SCR, McKay Boland P, Barve MA, Fritchie K, Seon BK, Alvarez D, Adams BJ, Shazer R, Theuer C, Maki R. A phase 1B/phase 2A study of TRC105 (Endoglin Antibody) in combination with pazopanib (P) in patients (pts) with advanced soft tissue sarcoma (STS). J Clin Oncol. 2016;34:(suppl; abstr 11016).
    1. Katz D, Peretz T, Eleyan F, Azraq Y, Merimsky O. Pazopanib plus sirolimus following escape from pazopanib alone: An intriguing observation—A series of 8 metastatic STS patients. J Clin Oncol. 2016;34:(suppl; abstr e22538).
    1. Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, et al. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016;17:1732–42. doi: 10.1016/S1470-2045(16)30507-1.
    1. Ray-Coquard I, Italiano A, Bompas E, Le Cesne A, Robin YM, Chevreau C, Bay JO, Bousquet G, Piperno-Neumann S, Isambert N, et al. Sorafenib for patients with advanced angiosarcoma: a phase II Trial from the French Sarcoma Group (GSF/GETO) Oncologist. 2012;17:260–6. doi: 10.1634/theoncologist.2011-0237.
    1. Hindi N, Pilotti S, Maestro R, Dei Tos A, Palassini E, Morosi C, Messina A, Provenzano S, Negri T, Fiore M, et al. Sunitinib malate in advanced alveolar soft part sarcoma (ASPS): A final update after the closure of the named use program. J Clin Oncol. 2015;33:(suppl; abstr 10562).
    1. Provenzano S, Maestro R, Dagrada G, Collini P, Pantaleo M, Astolfi A, Negri T, Gronchi A, Colombo C, Morosi C, et al. Sunitinib (SM) in advanced extraskeletal myxoid chondrosarcoma (EMC): Updated analysis in 11 patients (pts). J Clin Oncol. 2016;34:(suppl; abstr 11059).
    1. Stacchiotti S, Grosso F, Negri T, Palassini E, Morosi C, Pilotti S, Gronchi A, Casali PG. Tumor response to sunitinib malate observed in clear-cell sarcoma. Ann Oncol. 2010;21:1130–1. doi: 10.1093/annonc/mdp611.
    1. Hensley ML, Sill MW, Scribner DR, Jr, Brown J, Debernardo RL, Hartenbach EM, McCourt CK, Bosscher JR, Gehrig PA. Sunitinib malate in the treatment of recurrent or persistent uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study. Gynecol Oncol. 2009;115:460–5. doi: 10.1016/j.ygyno.2009.09.011.
    1. George S, Merriam P, Maki RG, Van den Abbeele AD, Yap JT, Akhurst T, Harmon DC, Bhuchar G, O'Mara MM, D'Adamo DR, et al. Multicenter phase II trial of sunitinib in the treatment of nongastrointestinal stromal tumor sarcomas. J Clin Oncol. 2009;27:3154–60. doi: 10.1200/JCO.2008.20.9890.
    1. Kummar S, Allen D, Monks A, Polley EC, Hose CD, Ivy SP, Turkbey IB, Lawrence S, Kinders RJ, Choyke P, et al. Cediranib for metastatic alveolar soft part sarcoma. J Clin Oncol. 2013;31:2296–302. doi: 10.1200/JCO.2012.47.4288.
    1. Chi Y, Sun Y, Cai J, Yao Y, Hong X, Fang Z, Sun P, Wang G, Wu Q, Qu G, et al. Phase II study of anlotinib for treatment of advanced soft tissues sarcomas. 2016 ASCO Annual Meeting. J Clin Oncol. 2016;34:(suppl; abstr 11005).
    1. Agulnik M, Costa RLB, Milhem M, et al. A phase II study of tivozanib in patients with metastatic and nonresectable soft-tissue sarcomas. Ann Oncol. 2017;28(1):121–7.
    1. Fu Y, Kang H, Zhao H, Hu J, Zhang H, Li X, Du N, Huang Y. Sunitinib for patients with locally advanced or distantly metastatic dermatofibrosarcoma protuberans but resistant to imatinib. Int J Clin Exper Med. 2015;8:8288–94.
    1. Kamar FG, Kairouz VF, Sabri AN. Dermatofibrosarcoma protuberans (DFSP) successfully treated with sorafenib: case report. Clin Sarcoma Res. 2013;3:5. doi: 10.1186/2045-3329-3-5.
    1. Schuetze SM, Bolejack V, Choy E, Ganjoo KN, Staddon AP, Chow WA, Tawbi HA, Samuels BL, Patel SR, von Mehren M, et al. Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor. Cancer. 2017;123:90–7. doi: 10.1002/cncr.30379.
    1. Schuetze SM, Wathen JK, Lucas DR, Choy E, Samuels BL, Staddon AP, Ganjoo KN, von Mehren M, Chow WA, Loeb DM, et al. SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. Cancer. 2016;122:868–74. doi: 10.1002/cncr.29858.
    1. Wagner AJ, Goldberg JM, Dubois SG, Choy E, Rosen L, Pappo A, Geller J, Judson I, Hogg D, Senzer N, et al. Tivantinib (ARQ 197), a selective inhibitor of MET, in patients with microphthalmia transcription factor-associated tumors: results of a multicenter phase 2 trial. Cancer. 2012;118:5894–902. doi: 10.1002/cncr.27582.
    1. Demetri GD, Chawla SP, Ray-Coquard I, Le Cesne A, Staddon AP, Milhem MM, Penel N, Riedel RF, Bui-Nguyen B, Cranmer LD, et al. Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy. J Clin Oncol. 2013;31:2485–92. doi: 10.1200/JCO.2012.45.5766.
    1. Benson C, Vitfell-Rasmussen J, Maruzzo M, Fisher C, Tunariu N, Mitchell S, Al-Muderis O, Thway K, Larkin J, Judson I. A retrospective study of patients with malignant PEComa receiving treatment with sirolimus or temsirolimus: the Royal Marsden Hospital experience. Anticancer Res. 2014;34:3663–8.
    1. Wagner AJ, Malinowska-Kolodziej I, Morgan JA, Qin W, Fletcher CD, Vena N, Ligon AH, Antonescu CR, Ramaiya NH, Demetri GD, et al. Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol. 2010;28:835–40. doi: 10.1200/JCO.2009.25.2981.
    1. Italiano A, Delcambre C, Hostein I, Cazeau AL, Marty M, Avril A, Coindre JM, Bui B. Treatment with the mTOR inhibitor temsirolimus in patients with malignant PEComa. Ann Oncol. 2010;21:1135–7. doi: 10.1093/annonc/mdq044.
    1. Stacchiotti S, Provenzano S, Dagrada G, Negri T, Brich S, Basso U, Brunello A, Grosso F, Galli L, Palassini E, et al. Sirolimus in advanced epithelioid hemangioendothelioma: a retrospective case-series analysis from the Italian Rare Cancer Network database. Ann Surg Oncol. 2016;23:2735–44. doi: 10.1245/s10434-016-5331-z.
    1. Quek R, Wang Q, Morgan JA, Shapiro GI, Butrynski JE, Ramaiya N, Huftalen T, Jederlinic N, Manola J, Wagner AJ, et al. Combination mTOR and IGF-1R inhibition: phase I trial of everolimus and figitumumab in patients with advanced sarcomas and other solid tumors. Clin Cancer Res. 2011;17:871–9. doi: 10.1158/1078-0432.CCR-10-2621.
    1. Wagner LM, Fouladi M, Ahmed A, Krailo MD, Weigel B, DuBois SG, Doyle LA, Chen H, Blaney SM. Phase II study of cixutumumab in combination with temsirolimus in pediatric patients and young adults with recurrent or refractory sarcoma: a report from the Children's Oncology Group. Pediatric Blood Cancer. 2015;62:440–4. doi: 10.1002/pbc.25334.
    1. Schwartz GK, Tap WD, Qin LX, Livingston MB, Undevia SD, Chmielowski B, Agulnik M, Schuetze SM, Reed DR, Okuno SH, et al. Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial. Lancet Oncol. 2013;14:371–82. doi: 10.1016/S1470-2045(13)70049-4.
    1. Endo M, Yamamoto H, Setsu N, Kohashi K, Takahashi Y, Ishii T, Iida K, Matsumoto Y, Hakozaki M, Aoki M, et al. Prognostic significance of AKT/mTOR and MAPK pathways and antitumor effect of mTOR inhibitor in NF1-related and sporadic malignant peripheral nerve sheath tumors. Clin Cancer Res. 2013;19:450–61. doi: 10.1158/1078-0432.CCR-12-1067.
    1. Dombi E, Baldwin A, Marcus LJ, Fisher MJ, Weiss B, Kim A, Whitcomb P, Martin S, Aschbacher-Smith LE, Rizvi TA, et al. Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med. 2016;375:2550–60. doi: 10.1056/NEJMoa1605943.
    1. Binh MB, Sastre-Garau X, Guillou L, de Pinieux G, Terrier P, Lagace R, Aurias A, Hostein I, Coindre JM. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surgical Pathol. 2005;29:1340–7. doi: 10.1097/01.pas.0000170343.09562.39.
    1. Dickson MA, Tap WD, Keohan ML, D'Angelo SP, Gounder MM, Antonescu CR, Landa J, Qin LX, Rathbone DD, Condy MM, et al. Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma. J Clin Oncol. 2013;31:2024–8. doi: 10.1200/JCO.2012.46.5476.
    1. Ray-Coquard I, Blay JY, Italiano A, Le Cesne A, Penel N, Zhi J, Heil F, Rueger R, Graves B, Ding M, et al. Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Lancet Oncol. 2012;13:1133–40. doi: 10.1016/S1470-2045(12)70474-6.
    1. Wilson BG, Wang X, Shen X, McKenna ES, Lemieux ME, Cho YJ, Koellhoffer EC, Pomeroy SL, Orkin SH, Roberts CW. Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell. 2010;18:316–28. doi: 10.1016/j.ccr.2010.09.006.
    1. Carter JM, O'Hara C, Dundas G, Gilchrist D, Collins MS, Eaton K, Judkins AR, Biegel JA, Folpe AL. Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with "neuroblastoma-like" schwannomatosis and a novel germline SMARCB1 mutation. Am J Surgical Pathol. 2012;36:154–60. doi: 10.1097/PAS.0b013e3182380802.
    1. Hornick JL, Dal Cin P, Fletcher CD. Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surgical Pathol. 2009;33:542–50. doi: 10.1097/PAS.0b013e3181882c54.
    1. Kohashi K, Oda Y, Yamamoto H, Tamiya S, Oshiro Y, Izumi T, Taguchi T, Tsuneyoshi M. SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma. Am J Surgical Pathol. 2008;32:1168–74. doi: 10.1097/PAS.0b013e318161781a.
    1. Kadoch C, Crabtree GR. Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell. 2013;153:71–85. doi: 10.1016/j.cell.2013.02.036.
    1. Agulnik M, Tannir NM, Pressey JG, et al. A phase II, multicenter study of the EZH2 inhibitor tazemetostat in adult subjects with INI1-negative tumors or relapsed/refractory synovial sarcoma. J Clin Oncol. 2016;34:(suppl; abstr TPS11071).
    1. Mackall C, D’Angelo S, Grupp S, Glod J, Druta M, Chow W, Chagin K, Mehler M, Kari G, Trivedi T, et al. Open label non-randomized multi-cohort pilot study of genetically engineered NY-ESO-1 specific NY-ESO-1c259 SPEAR T-cellsTM in HLA-A*02+ patients with synovial sarcoma (NCT01343043) Ann Oncol. 2016;27(Suppl_6):1075P. doi: 10.1093/annonc/mdw378.29.
    1. Tawbi HAH, Burgess M, Crowley J, Van Tine B, Hu J, Schuetze S, D’Angelo S, Attia S, Priebat D, Okuno S, Riedel R, et al. Safety and efficacy of PD-1 blockade using pembrolizumab in patients with advanced soft tissue (STS) and bone sarcomas (BS): Results of SARC028—A multicenter phase II study. J Clin Oncol. 2016;34;(suppl; abstr 11006).
    1. Italiano A, Penel N, Chevreau C, Blay J, Le Cesne A, Bompas E, Piperno-Neumann S, Cousin S, Ryckewaert T, Pulido M, et al. Combination of pembrolizumab and metronomic cyclophosphamide in patients with advanced sarcomas: a French Sarcoma Group study. In: 2016 Connective Tissue Oncology Society Annual Meeting, Lisbon, 9–12 November, 2016. p. 139. .
    1. Paoluzzi L, Cacavio A, Ghesani M, Karambelkar A, Rapkiewicz A, Weber J, Rosen G. Response to anti-PD1 therapy with nivolumab in metastatic sarcomas. Clin Sarcoma Res. 2016;6:24. doi: 10.1186/s13569-016-0064-0.
    1. Heine A, Kristiansen G, Schild HH, Brossart P. Successful treatment of refractory leiomyosarcoma with the PD-1 inhibitor nivolumab. Ann Oncol. 2016;27:1813–4. doi: 10.1093/annonc/mdw243.
    1. George S, Barysauskas CM, Solomon S, Tahlil K, Malley R, Hohos M, Polson K, Loucks M, Wagner AJ, Merriam P, et al. Phase 2 study of nivolumab in metastatic leiomyosarcoma of the uterus. J Clin Oncol. 2016;34:(suppl; abstr 11007).

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