A multicenter, randomized controlled trial of intrapleural drug-loaded vesicle perfusion combined with systemic therapy for malignant pleural effusion.

3152 Background: This study aimed to evaluate the efficacy and safety of drug-loaded vesicle (DLV) intrapleural perfusion combined with systemic therapy in patients with lung or breast cancer and malignant pleural effusion (MPE). Methods: This multicenter, randomized, controlled, open-label clinical trial included patients with pathologically confirmed lung or breast cancer and MPE requiring thoracentesis. In total, 96 patients were randomised 1:1 to arm 1 receiving DLV intrapleural perfusion (50 mL daily for four consecutive days) plus systemic therapy (ST) or arm 2 receiving interleukin-2 (IL-2) intrapleural perfusion (50 mL every three days for three sessions) with ST.The primary endpoint was the objective response rate (ORR) of pleural effusion at 4 weeks post-perfusion, while secondary endpoints included overall survival (OS) and treatment-related toxicity.The difference in ORR between the two cohorts was analyzed using the Chi-square test. Kaplan-Meier survival analysis was performed for OS comparison between the two cohorts. Results: A total of 91 patients were evaluated for efficacy (50 in arm 1 and 41 in arm 2). The DLV+ST arm 1 showed a significantly higher ORR for pleural effusion than the IL-2+ST arm 2 (74.0% vs. 53.7%, P = 0.043). In the survival analysis of 83 evaluable patients, median OS was 15.0 months (95% CI: 9.2–26.9) in arm 1 and 6.9 months (95% CI: 5.3–15.8) in arm 2, without a statistically significant difference (HR = 0.75; 95% CI: 0.46–1.24; P = 0.266). The 1-, 2-, and 3-year OS rates for arm 1 were 83.0% (95% CI: 72.9–94.4%), 59.6% (95% CI: 47.1–75.4%), and 51.1% (95% CI: 38.6–67.6%), compared to arm 2's 69.4% (95% CI: 55.9–86.2%), 41.7% (95% CI: 28.3–61.3%), and 33.3% (95% CI: 21.0–52.9%). Both arms had similar safety profiles, with chemotherapy-induced toxicities, including leukopenia, gastrointestinal reactions, and liver dysfunction, being the most common treatment-related adverse events. Conclusions: Drug-loaded vesicle intrapleural perfusion combined with systemic therapy is a safe and effective treatment option for malignant pleural effusion in patients with lung or breast cancer. This approach represents a promising treatment strategy for MPE and warrants further clinical investigation and consideration in clinical practice. Clinical trial information: ChiCTR1800017104 .