Preliminary results of pegylated liposomal doxorubicin, dacarbazine, and toripalimab in patients with advanced primary cardiac sarcoma: An interim analysis.

11575 Background: Primary cardiac sarcoma (PCS) is an ultra-rare malignancy with a dismal prognosis, with previously reported median overall survival (OS) of 8–17.2 months. The roles of chemotherapy and immunotherapy remain controversial, and prospective evidence is scarce. We conducted a prospective, single-arm study to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD), dacarbazine (DTIC), and toripalimab in patients with advanced PCS (DART-PCS). Methods: Patients with locally advanced or metastatic PCS were enrolled from January 2024. Treatment consisted of PLD (35–40 mg/m²) and DTIC (1.0–1.2 g/m²), each administered either on day 1 or divided over days 1–2, plus toripalimab (240 mg, day 1), every 3 weeks for six cycles. Tumor responses were assessed every two cycles by CT or MRI. Patients without progression after six cycles underwent multidisciplinary evaluation to determine further combination therapy or immunotherapy maintenance. The primary endpoint was investigator-assessed overall response rate (ORR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), OS, and safety. Adverse events (AEs) were graded using CTCAE v5.0. Survival outcomes were estimated using the Kaplan–Meier method. The planned sample size was 30 patients. Results: To data cutoff, a total of 20 patients were enrolled (65% male; median age: 36 years). ECOG performance status was 0 in 30%, 1 in 45%, and 2 in 25% of patients. Eighteen patients (90%) had undergone prior surgical resection, although R0 resection was achieved in only 25%. Histologies included angiosarcoma (85%), pleomorphic undifferentiated sarcoma (10%), and epithelioid hemangioendothelioma (5%). All tumors originated in the atrium, with right atrial involvement in 85% and left atrial involvement in 15%. At enrollment, 12 patients (60%) presented with metastatic disease, and 8 (40%) had local recurrence. Responses were evaluable in 18 patients. The ORR was 44.4%, including 3 complete and 5 partial responses. The median duration of response was 21.8 weeks (95%CI: 11.7-32.0). As of January 15, 2026, the median PFS was 23.1 weeks (95%CI: 18.21-29.22), and the median OS 55.0 weeks (95%CI: 37.21-72.78). The 1-year OS rate was 54%. Treatment-related adverse events (TRAEs) occurred in all patients, with grade ≥3 TRAEs observed in 18 (90%) patients, most commonly neutropenia (90%), leucopenia (40%) and anemia (30%). One fatal serious AE (hemoptysis) was reported. The median cumulative PLD dose was 221.6 mg/m 2 (range: 69.0-465.1). No clinically significant cardiac dysfunction were observed. Conclusions: Preliminary results from the DART-PCS trial demonstrate promising antitumor activity and an acceptable safety profile for PLD, DTIC, and toripalimab in patients with advanced PCS. Further validation is warranted upon completion of the study. Clinical trial information: ChiCTR2400084334.