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Table 3 Kinase-inhibitors in soft tissue sarcomas: prospective evidence

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

Study Population Study phase Drug and schedule Patients Overall response rate (%) Progression-free survival (months) Overall survival (months)
Tyrosine-kinase inhibitors
George et al., 2009 [60] Metastatic all-type STS Phase II Sunitinib 37.5 mg once daily 53 2 1.8 NA
Hensley et al., 2009 [59] Advanced uterine LMS Phase II Sunitinib 50 mg daily, 4 weeks on, 2 weeks off 25 9 1.5 NA
Rutkowski et al., 2010 [19] DFSP Pooled analysis of two phase II Imatinib 400–800 mg daily 34 32 20.4 Unreached
Wagner et al., 2012 [68] MTF-associated tumours (including ASPS, CCS) Phase II Tivantinib 120 mg, twice daily 47 2 3.6 NA
van der Graaf et al., 2012 [45] Metastatic, non-adipocytic STS Randomised, phase III Arm A: pazopanib 800 mg daily
Arm B: placebo
Arm A: 246
Arm B: 123
Arm A: 6
Arm B: 0
Arm A: 4.6
Arm B: 1.6
Arm A: 12.5
Arm B: 10.7
Ray-Coquard et al., 2012 [55] Advanced superficial (stratum A) and visceral (stratum B) angiosarcoma Phase II Sorafenib 400 mg twice daily Stratum A: 26
Stratum B: 15
Stratum A: 15
Stratum B: 13
Stratum A: 1.8
Stratum B: 3.8
Stratum A: 12
Stratum B: 9
Kummar et al., 2013 [61] Advanced ASPS Phase II Cedinarib 30 mg daily 46 35   
Mir et al., 2016 [54] Cohort A: LPS
Cohort B: LMS
Cohort C: SS
Cohort D: other sarcomas
Randomised, phase II Arm A: regorafenib 160 mg/day 3 weeks on, 1 week off
Arm B: placebo
Cohort A: 43
Cohort B: 56
Cohort C: 27
Cohort D: 56
Cohort A: 0 (arm A) vs. 0 (arm B)
Cohort B: 0 (arm A) vs. 4 (arm B)
Cohort C: 8 (arm A) vs. 0 (arm B)
Cohort D: 11 (arm A) vs. 0 (arm B)
Cohort A: 1.1 (arm A) vs. 1.7 (arm B)
Cohort B: 3.7 (arm A) vs. 1.8 (arm B)
Cohort C: 5.6 (arm A) vs. 1 (arm B)
Cohort D: 2.9 (arm A) vs. 1 (arm B)
Cohort A: 4.7 (arm A) vs. 8.8 (arm B)
Cohort B: 21 (arm A) vs. 9.1 (arm B)
Cohort C: 13.4 (arm A) vs. 6.7 (arm B)
Cohort D: 12.1 (arm A) vs. 9.5 (arm B)
Chi et al., 2016 [62] Metastatic all-type STS Phase II Anlotinib 12 mg daily, 2 weeks on, 1 week off 166 11 5.6 NA
Agulnik et al., 2016 [87] Metastatic all-type STS Phase II Tivozanib 1.5 mg daily, 3 week on, 1 week off 58 3.6 3.5 12.2
Schuetze et al., 2016 [67] Metastatic all-type STS Phase II Dasatinib 100 mg twice daily 200 1 1.9 8
Schuetze et al., 2017 [66] Metastatic ASPS, CS, chordoma, ES, SFT Phase II Dasatinib 100 mg twice daily 116 <1 5.8 21.6
Serine/threonine kinase inhibitors
Demetri et al., 2013 [69] Metastatic all-type STS and BS (responsive/stable on CHT) Randomised, phase III Arm A: ridaforolimus 40 mg once daily, 5 days every week
Arm B: placebo
Arm A: 347
Arm B: 364
NA Arm A: 17.7
Arm B: 14.6
Arm A: 21
Arm B: 19.8
Schwartz et al., 2013 [76] Metastatic all-type STS and BS Phase II Cixutumumab (6 mg/kg) and temsirolimus (25 mg) 174 5 NA NA
Dickson et al., 2013 [80] Advanced CDK4-amplified WDLPS/DDLPS Phase II PD0332991 200 mg orally once daily, 2 weeks on, 1 week off 30 3 18 NA
  1. ASPS alveolar soft part sarcoma; BS bone sarcomas; CCS clear cell sarcoma; CHT chemotherapy; CS chondrosarcoma; DDLPS dedifferentiated liposarcoma; DFSP dermatofibrosarcoma protuberans; ES epithelioid sarcoma; LMS leiomyosarcoma; LPS liposarcoma; MTF microphthalmia transcription factor; NA not available; OS osteosarcoma; SFT solitary fibrous tumour; SS synovial sarcoma; STS soft tissue sarcomas; UPS undifferentiated pleomorphic sarcoma; WDLPS well-differentiated liposarcoma
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