Maintenance after first-line treatment for advanced soft tissue sarcoma

Doxorubicin-based chemotherapy remains the best treatment modality for patients with advanced soft tissue sarcoma (STS), despite limited therapeutic efficacy. Moreover, subsequent salvage treatments exhibit reduced effectiveness. Consequently, the investigation of maintenance therapy in patients with non-progressive STS is pertinent. We reviewed non-randomized trials, although their interpretation was constrained by the lack of internal comparators. We examined eight randomized trials investigating maintenance therapy in patients with STS. Among seven trials assessing continuation maintenance therapy, two demonstrated significant improvement in progression-free survival (PFS): trabectedin following doxorubicin/trabectedin treatment in patients with advanced/metastatic leiomyosarcoma and anlotinib following epirubicin/anlotinib treatment across all histological subtypes. One trial investigating switch maintenance with regorafenib reported significant improvement in PFS in patients with nonadipocytic STS. Doxorubicin/trabectedin in patients with leiomyosarcoma yielded significant improvement in overall survival. Promising results observed with olaratumab in a randomized phase II trial were not confirmed in a subsequent phase III trial. Early phase trials involving doxorubicin/trabectedin in patients with liposarcoma, doxorubicin/lurbinectedin in patients with leiomyosarcoma and those with liposarcoma, and doxorubicin/pembrolizumab revealed promising associations that warrant exploration in future randomized trials. For pembrolizumab, biomarkers for appropriate patient selection are lacking. This literature review can aid in the design of future maintenance trials.