ABSTRACT
Introduction: Soft-tissue sarcomas (STS) are a heterogeneous group of diseases that are characterized by a historic lack of active treatment options. However, several new drugs and indications have become available in recent years.
Areas covered: This article reviews the most relevant phase II studies that utilize chemotherapy agents (aldoxorubicin, amrubicin, trabectedin alone or in combination with doxorubicin, and gemcitabine plus docetaxel), targeted therapies (Imatinib, dasatinib, regorafenib, tivozanib, palbociclib and selinexor), a combination of chemotherapy plus targeted therapies (fucusing on doxorubicin plus olaratumab) and immunotherapies (pembrolizumab, combination of nivolumab plus ipilimumab and adaptive cell therapy) in STS (other than gastrointestinal stromal tumors) (GIST) published from 2015. Some of these strategies are under further clinical development or will likely be assessed in future phase III studies.
Expert opinion: A series of novel treatments have shown encouraging results in STS in recent years. The most important is the combination of the standard cytotoxic agent doxorubicin plus the platelet-derived growth factor receptor (PDGFR) inhibitor olaratumab, although definitive results from a phase III trial are expected. Immunotherapy has not been as successful in STS so far. However, further investigations are ongoing.
Article Highlights
Several phase II clinical trials in STS with new chemotherapy strategies such as aldoxorubicin, amrubicin, trabectedin alone or in combination with doxorubicin, and gemcitabine plus docetaxel have been recently published.
Imatinib, dasatinib, regorafenib, tivozanib, palbociclib and selinexor have also been recently assessed in STS in phase II clinical trials.
Some combinations of chemotherapy plus targeted agents have also been evaluated. Among them, doxorubicin and olaratumab is the most important advance in STS in decades although confirmatory results from a phase III trial are eagerly awaited.
Immunotherapies such as pembrolizumab, combination of nivolumab and ipilimumab or adaptive cell therapy have recently shown signs of activity in some STS subtypes. Further development is needed.
To find new standard therapeutic options in STS, it is necessary to achieve a deeper understanding of their biology and to carefully select patients and tumor types for phase III clinical trials.
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Declaration of interest
X García del Muro has disclosed an advisory role in Lilly and Pharmamar. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose