Abstract
Anthracycline-based chemotherapy remains the cornerstone of first-line systemic treatment for most subtypes of advanced soft tissue sarcoma (STS). However, cumulative cardiotoxicity and a decline in quality of life limit the treatment duration of free-form anthracycline, restricting its long-term benefits. Maintenance therapy-defined as the continuation of a less toxic systemic treatment following initial disease control-includes two main strategies: continuation maintenance and switch maintenance. Continuation maintenance involves the extended use of the same agent or one with a similar mechanism of action to preserve the efficacy of the prior treatment while minimizing the toxicities. By contrast, switch maintenance uses a different, potentially less toxic agent to extend disease control after prior treatment. Both approaches are established in other solid tumors and have been explored in STS. The LMS-04 trial demonstrated improved outcomes with doxorubicin plus trabectedin induction followed by trabectedin maintenance in leiomyosarcoma patients. However, this strategy is limited to leiomyosarcoma patients who received first-line doxorubicin plus trabectedin and is associated with high-grade toxicity (grade 3/4 adverse events in 97% of patients). Switch maintenance strategies, such as ridaforolimus and regorafenib, have limitations in efficacy and tolerability, preventing their widespread adoption. Pegylated liposomal doxorubicin (PLD), a liposome-encapsulated formulation of doxorubicin, offers a potential continuation maintenance option. With a similar mechanism of action to free-form anthracycline but reduced cumulative cardiac toxicity, PLD may be both effective and better tolerated in STS patients who have derived benefit from anthracycline-based chemotherapy. A clinical trial investigating continuation maintenance PLD in this patient population is warranted.