Abstract 87P
Background
Soft tissue sarcomas (STS) are heterogeneous cancers with variegate biological features and limited treatments. Multi-target tyrosine-kinase inhibitors (TKIs) showed efficacy and tolerability in the treatment of STS. However, their effects vary based on STS histology and patients’ characteristics.
Methods
We performed a systematic research of literature in Pubmed-indexed journals to find trials testing TKIs as monotherapy in patients with advanced STS, except gastrointestinal stromal tumors (GIST). We assessed pooled Disease Control Rate (DCR), Objective Response Rate (ORR) and safety. We performed a subgroup analysis based on different TKIs. Pooled efficacy was assessed with a random-effects model using the restricted maximum likelihood method. Logit transformation of data was implemented when the individual study proportion was <0.2 or >0.8. We used the arcsine transformation for studies with zero events. The statistical significance threshold was set at a P £ .05. Sensitivity analyses were conducted with a leave-one-out method.
Results
Twenty-nine trials were selected for further analysis, including 1573 patients. Leiomyosarcoma (n=429), synovial sarcoma (n= 176) and solitary fibrous tumor (n=124) were the most represented histotypes. Pazopanib was the top tested TKI, used in 11 trials. Pooled analysis showed a DCR of 62.6% (95% CI: 55.7% - 69.1%), with no difference based on various TKIs (pazopanib: 65.1%; 95% CI: 53.8%-75.0%; other TKIs: 61.3%; 95% CI: 55.7%-69.1%). TKIs demonstrated limited response with a cumulative ORR of 7.5% (95% CI: 5.6% - 9.6%), without major discrepancies based on different drugs. Leave-one-out analysis did not show significant impact of any of the selected trials in the overall effect size. In the selected trials, the discontinuation rate was 13.9% (95% CI: 8.2%-20.8%). The most common treatment-related adverse events were fatigue (47%), hypertension (37%) and diarrhoea (33%).
Conclusions
TKIs guarantee a valid DCR and a manageable safety profile in patients with advanced STS. Further larger studies are needed to clarify their efficacy in different STS histotypes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.