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Table 5 Previous studies about target therapy on sarcoma

From: Apatinib for advanced sarcoma: results from multiple institutions’ off-label use in China

Drug Combined with chemotherapy The first author’s last name Year of publication Trial Sponsor Number of patients (N) Clinical outcome
osteosarcoma
  GT Elizabeth Fox 2012 SARTCSf 14 ORR 7.1%;
Sorafenib no Grignani 2011 Italian Sarcoma Group 35 4 m-PFSa 46%; DRd 4 m; ORRc14%;
Trastuzumab Cytotoxic Chemotherapy Ebb 2012 COGe 41 30 m-EFS 32%; 30 m-OSb 50%; without significant difference comparing with control group
Sirolimus Cyclophosphamide Schuetze 2012 Michigan University 5 ORR 0%; 4 m-PFS 30% (combined with other sarcoma)
Cixutumumab and Temsirolimus no Schwartz 2013 MSKCCg fund 24 ORR 13%; median PFS 6w
Cixutumumab no Weigel 2014 COG 11 ORR 0%; 1/11 SD for 140 d
R1507 no Pappo 2014 SARTCSf 38 ORR 2.5%; DR: 12w; 12w-PFS 17%
Sorafenib; Everolimus no Grignani 2015 Italian Sarcoma Group 38 6 m-PFS 45%; DR 5 m; ORR 10%
Cixutumumab; Temsirolimus no Wagner 2015 COG 11 ORR 0%;
Dasatinib no Schuetze 2016 SARTCS 46 ORR 6.5%; DR 5.7 m; 2y-OS 15%
Apatinib no Present study 2017   22 ORR 40.9%;median PFS 3.1 m; 4 m PFS 24.1%; 6 m PFS 18.1%
Ewing sarcoma
  GT Elizabeth Fox 2012 SARTCS 14 ORR 14.3%;
R1507 no Pappo 2011 SARTCS 115 ORR 9.6%; median PFS 1.3 m; median OS 7.6 m
Figitumumab no Juergens 2011 European organization 106 ORR 14.2%; median PFS 1.9 m; median OS 8.9 m
Cixutumumab + temsirolimus no Schwartz 2013 MSKCC 27 ORR 14.8%; median PFS 7.5w; median OS 16.2 m
Olaparib no Choy E 2014 MGHh 12 ORR 0%; DR 5.7w;
Cixutumumab + temsirolimus no Wagner LM 2015 COG 43 ORR 0%; 12w-PFS 16%;
Apatinib+everolimus & apatinib alone no Present study 2017   10 ORR 70%; median PFS 2.0 m; 12w-PFS 22.5%
Soft tissue sarcoma
  Topotecan +carboplatin Bochennek K 2013 CSTSGi 34 ORR 38%;
Pazopanib no Winette T A 2012 EORTCj and the PALETTE study group 246 ORR 6%; median PFS 4.6 m; median OS 12.5 m
Olaratumab Doxorubicin William D Tap 2016 MSKCC and 16 clinical sites in US 15 in IB trial and 67 in II trial ORR 18.2%; median PFS 6.6 m; median OS 26.5 m
Regorafenib no Thomas Brodowicz 2015 International trial (France, Austria, Germany) 82 Median PFS 5.6 m for SS and 2.9 m for none specific;
Apatinib alone & apatinib+everolimus Sometimes accompanied with GTk Present study 2017   21 ORR 71.4%; median PFS 6.6 m; 4 m-PFS 71.4%; median OS 9.9 m
chondrosarcoma
  GT Elizabeth Fox 2012 SARTCS 25 ORR 8%;
GDC-0449 no A. Italiano 2013 French Sarcoma Group/US; French National Cancer Institute 39 ORR 0%; median PFS 3.5 m; 6-m PFS 28.2%; 1-y PFS 19.2%
Imatinib no Grignani 2011 Italian Sarcoma Group 26 ORR 0%; 4 m-PFS 31%; median OS 11 m;
Sirolimus cyclophosphamide Bernstein-Molho R 2012 Israel 10 ORR 10%; 60% SD for more than 6 m; median PFS 13.4 m
IDHl inhibitor no NCT02273739;
NCT02481154;
NCT02073994;
NCT02496741
2016–2017    Under investigations
Apatinib alone no Present study 2017   3 ORR 100%; median PFS 7.37
  1. aPFS: progression-free survival
  2. bOS: overall survival
  3. cORR: overall response rate, defined as complete responses (CRs) + partial responses (PRs) + MRs;
  4. dDR: Duration of response
  5. eCOG: Children’s Oncology Group
  6. fSARTCS: Sarcoma Alliance for Research Through Collaboration Study
  7. gMSKCC: Memorial Sloan-Kettering Cancer Center
  8. hMGH: Massachusetts General Hospital
  9. iCSTSG: Cooperative Soft Tissue Sarcoma Group
  10. jEORTC: European Organization for Research and Treatment of Cancer
  11. kGT: chemo-protocol combined with gemcitabine 1000 mg/m2 d1,8 and docetaxel 75 mg/m2 d8
  12. lIDH: isocitrate dehydrogenase