Table 5.

Randomized trials investigating the use of systemic therapy in the treatment of locally advanced or metastatic soft tissue sarcoma

Trial	Study design	N	Objective response rate	Progression-free survival	Overall Survival	Conclusions
Maki 2007 [92]	Phase II: Gemcitabine + docetaxel versus gemcitabine	122	16% versus 8%	6.2 versus 3 mo	18 versus 12 mo	Combination superior but has increased toxicity (prohibitive of long-term use)
Lorigan 2007 [84]	Phase III: Two investigational schedules of ifosfamide versus doxorubicin	326	8.4% versus 5.5% versus 11.8% NS	3.0 versus 2.16 versus 2.52 NS	10.92 versus 10.92 versus 12.0 NS	Increased toxicity with ifosfamide with no benefit over doxorubicin alone
Garcia-Del-Muro 2011 [94]	Phase II: Gemcitabine + dacarbazine versus gemcitabine	113	49% versus 25% P=0.009	4.2 versus 2 mo P=0.005	16.8 versus 8.2 mo P=0.014	Combination superior and well tolerated, no increased toxicity
PALETTE van der Graaf 2012 [90]	Phase III: Pazopanib versus placebo in non-adipocytic STS	369	6% versus 0%	4.6 versus 1.6 mo P<0.0001	12.5 versus 10.7 mo P=0.25	Superior disease control with pazopanib, acceptable toxicity
TAXOGEM Pautier 2012 [93]	Phase II: Gemcitabine + docetaxel versus gemcitabine in LMS	44 (non-uterine LMS only)	5% versus 14%	3.4 versus 6.3 mo NS	13 versus 15 NS	Increased toxicity with combination with no difference in disease control
EORTC 62012 Judson 2014 [81]	Phase III: Doxorubicin + ifosfamide versus doxorubicin	455	26% versus 14% P<0.0006	7.4 versus 4.6 mo P=0.03	14.3 versus 12.8 mo P=0.076	No benefit to combination for palliation of advanced STS unless the goal of treatment is tumor shrinkage
GeDDiS Seddon 2015 [79]	Phase III: Gemcitabine + docetaxel versus doxorubicin	257	N/A	5.5 versus 5.4 mo P=0.07	14.5 versus 16.4 mo P=0.67	Increased toxicity with combination with no difference in disease control
Demetri 2016 [87]	Phase III: Trabectedin versus dacarbazine in LPS and LMS	518	9.9% versus 6.9% P=0.33	4.2 versus 1.5 moP <0.0001	12.4 versus 12.9 mo P=0.37	Superior disease control with trabectedin. Led to FDA approval
Ryan 2016 [77]	Phase III: Doxorubicin + palifosfamide versus doxorubicin	447	28.3% versus 19.9%	6.0 versus 5.2 moP=0.19	15.9 versus 16.9 mo P=0.74	Increased toxicity with combination with no difference in disease control
Tap 2016 [80]	Phase II: Doxorubicin + olaratumab versus doxorubicin	133	18.2% versus 11.9% P=0.3421	6.6 versus 4.1 mo P=0.06	26.5 versus 14.7 mo P=0.0003	Highly significant 11.8-mo survival benefit with olaratumab
Schoffski 2016 [89]	Phase III: Eribulin versus dacarbazine in LPS and LMS	452	4% versus 5% P=0.62	2.6 versus 2.6 mo P=0.229	13.5 versus 11.5 mo P=0.0169	Survival benefit with eribulin in LPS and LMS

STS, soft tissue sarcoma; LPS, liposarcoma; LMS, leiomyosarcoma; NS, not significant; mo, months.