Triplet combination of anlotinib plus nab-paclitaxel and gemcitabine (AG) as a first-line strategy for advanced primary cardiac angiosarcoma: A high-volume center experience.

11562 Background: Primary cardiac angiosarcoma (PCAS) is an exceedingly rare and lethal mesenchymal malignancy characterized by aggressive growth and high metastatic potential. Despite the use of taxane-based regimens, the prognosis remains dismal, with a historical median overall survival (mOS) of approximately 11 months. Given the highly vascular nature of PCAS, we hypothesized that integrating a multi-target anti-angiogenic TKI (anlotinib) with cytotoxic chemotherapy could synergistically improve outcomes. This study evaluated the efficacy and safety of anlotinib plus nab-paclitaxel and gemcitabine (AG) in advanced PCAS. Methods: We retrospectively analyzed patients with metastatic or unresectable PCAS treated at Zhongshan Hospital, Fudan University. The triplet regimen consisted of anlotinib (8-12 mg QD, days 1-14, q3w), nab-paclitaxel (200 mg), and gemcitabine (1000 mg/m²) on days 1 and 8 every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety (CTCAE v5.0). Survival outcomes were estimated using the Kaplan-Meier method and compared via log-rank tests. Results: A total of 24 patients were included, with a median age of 44 years. Most tumors (91.7%) originated in the right atrium, and 70.8% of patients received this regimen as first-line therapy. Efficacy: At a median follow-up of 31.4 months, the ORR was 62.5% and the DCR was 95.8%. Survival: The median PFS was 9.5 months (95% CI, 8.4-20.7). Notably, the median OS reached 24.9 months (95% CI, 15.2-NR), significantly exceeding historical benchmarks. Prognostic Indicators: Subgroup analysis identified liver metastasis (45.8%) as a significant negative prognostic factor for PFS (p = 0.018). Additionally, a numerical trend toward shorter survival was observed in patients with baseline D-dimer > 5 mg/dL (Median OS: 5.5 vs. 10.5 months; p = 0.428). Safety: Treatment-related adverse events (TRAEs) of any grade occurred in 95.8% of patients. Grade≥3 TRAEs (41.7%) were primarily hematological (neutropenia, thrombocytopenia) and were manageable via dose modification. No severe treatment-related cardiotoxicity was observed. Conclusions: The triplet combination of anlotinib and AG demonstrates unprecedented survival benefits and a manageable safety profile in advanced PCAS. With a mOS exceeding twice the historical data, this regimen represents a potent new treatment strategy. Liver involvement serves as a critical prognostic indicator for risk stratification, while the clinical significance of baseline D-dimer levels as a surrogate marker for tumor burden warrants further investigation in larger cohorts.