Advances of systemic treatment for adult soft-tissue sarcoma
Soft-tissue sarcoma (STS) is a group of rare but highly heterogeneous neoplasms. Systemic treatment with cytotoxic chemotherapy and targeted agents is one of the main therapeutic modalities in patients with unresectable or metastatic disease, while adjuvant and neoadjuvant chemotherapy for adult-type sarcomas remain controversial. Although an anthracycline (doxorubicin) and ifosfamide remain the cornerstone for chemotherapy, advances have been made recently to exceed its limited efficacy, other agents such as trabectedin, eribulin have been approved. In a recent study, the addition of platelet-derived growth factor receptor (PDGFR) antibody-olaratumab to doxorubicin resulted in prolongation of progression-free survival and overall survival, which really means a breakthrough for STS. There is more emerging evidence of different sensitivity to treatment for different histological subtypes, second-line treatment for advanced sarcoma is being increasingly driven by histology. Cytotoxic drugs such as dacarbazine, gemcitabine, and taxanes have shown moderate activity in specific subtypes. Tyrosine kinase inhibitors (TKIs), including pazopanib and anlotinib, appear to be the promising targeted therapies. Other signal pathway inhibitors as CDK4/CDK6 inhibitor, imatinib, mTOR inhibitors, ALK inhibitor has shown some preliminary effect that need to be verified in the future trials. Checkpoint inhibitors as anti-PD-1 and CTLA-4 monoclonal antibodies have been used as a single agent or in combination in the early clinical trials, while further research needs to focus on better patient selection and new combinational strategies. In this review, we aim to summarize the advances of chemotherapy, targeted therapy and immunotherapy in the management of STS.