Maintenance pegylated liposomal doxorubicin (PLD) versus active surveillance for advanced soft tissue sarcoma patients who had controlled disease after standard anthracycline-based treatment (MELODY).

Abstract

TPS11596 Background: The progression-free survival (PFS) associated with first-line chemotherapy for advanced soft tissue sarcoma (STS) remains unsatisfactory. Extending treatment with an active agent that has demonstrated clinical benefit in a patient (pt)—the maintenance therapy—may offer an opportunity to further delay disease progression. While anthracyclines are the current standard first-line treatment, their cumulative cardiotoxicity limits prolonged use. Pegylated liposomal doxorubicin (PLD) offers a more favorable cardiac safety profile, representing a viable option for extended treatment. Methods: MELODY is a randomized, multinational clinical trial designed to evaluate the clinical benefit of maintenance PLD in pts with advanced STS who have achieved disease control following anthracycline-based therapy. The study incorporates patient-reported outcomes (PROs) to explore the balance between extended treatment and active surveillance from the patient’s perspective—providing a more holistic understanding of the value of maintenance therapy in this population. Built-in translational studies aim to identify biomarkers that better select pts most likely benefit from maintenance therapy, thereby further personalizing treatment strategies in advanced STS. Eligible criteria include advanced STS patients aged ≥ 18 who had either CR, PR, or SD after first-line anthracycline-based therapy (at least five cycles). Pts will be randomized 2:1 to the experimental arm: PLD (40 mg/m² every 28 days, up to 12 cycles) or the control arm: active surveillance. The primary endpoint is progression-free survival (PFS) post randomization. Patients in the active surveillance arm will not crossover to PLD upon progression. Secondary endpoints include QoL by EORTC C30 questionnaire, OS, 12-month PFS rate, ORR by RECIST 1.1, and time to next treatment. Left ventricular ejection fraction (LVEF) change will be an interest of safety. Exploratory objectives include efficacy endpoints (PFS, OS, 12-month PFS rate) based on circulating tumor DNA (mandatory) and FDG PET/CT SUVmax (Optional). Based on our systematic review (Lee MJ et al. Ther Adv Med Oncol 2025), the mPFS for the control arm is estimated to be 4 months. A clinically meaningful improvement is anticipated in the experimental arm, with a mPFS of 8 months. Assuming 80% power and an alpha level of 0.1, a total of 63 evaluable subjects are required. Accounting for an anticipated 20% drop-out rate, MELODY plans to enroll a total of 81 subjects. Clinical trial information: NCT06981637 .