Efficacy and safety of disitamab vedotin combination therapy in HER2-positive advanced gynecological cancers: A multicenter retrospective analysis.

e17534 Background: Disitamab vedotin (RC48), an antibody-coupled drug, has demonstrated clinical benefits in HER2-expressing gynecological cancers. However, its clinical application in these malignancies remains limited, and the impact of combination treatments involving disitamab vedotin is not yet fully understood. This study aimed to assess the efficacy and safety of disitamab vedotin combination therapy in patients with HER2-positive advanced gynecological cancers. Methods: We conducted a multicenter, real-world retrospective analysis of patients with HER2-positive advanced gynecological cancers treated with disitamab vedotin (120 mg administered intravenously every three weeks). Baseline characteristics, efficacy outcomes, and adverse event data were collected. The primary endpoint was the objective response rate (ORR) based on RECIST version 1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between January 6, 2023, and December 26, 2024, a total of 48 patients (median age, 55.5 years; range, 33–74) were enrolled. The most common tumor types were cervical cancer (73.0%), endometrial cancer (13.5%), and ovarian cancer (13.5%). HER2 expression levels were IHC 1+ (50%), IHC 2+ (43.8%), and unknown (6.3%). Overall, 62.2% of patients had received at least two prior lines of treatment. All patients underwent disitamab vedotin combination therapy, with disitamab vedotin plus immunotherapy being the most common regimen (79.2%). Efficacy was evaluable in 38 patients, who demonstrated an ORR of 65.8% (95% CI: 50.0–81.6) and a DCR of 86.8% (95% CI: 75.6–98.1). Among patients with HER2 IHC 1+, the ORR was 76.5% (95% CI: 54.0–99.0), whereas patients with HER2 IHC 2+ had an ORR of 55.0% (95% CI: 31.1–78.9). In patients receiving disitamab vedotin combined with immunotherapy, the ORR was 61.3% (95% CI: 43.1–79.5). The median PFS was 8.8 months (95% CI: 6.5–11.4), and the median OS was 20.4 months (95% CI: 14.6–not reached). Adverse events occurred in 73.3% of patients, predominantly grade 1–2 (64.4%), with the most common being anemia (57.8%), lymphocytopenia (53.3%), and hypoalbuminemia (37.8%). Grade ≥3 adverse events occurred in 8.9% of patients, primarily lymphopenia (8.9%) and elevated GGT (6.7%). No RC48-related deaths were reported. Conclusions: This study suggests that RC48-based combination therapy is both effective and tolerable in patients with HER2-positive advanced gynecological cancers, including those with HER2 IHC 1+ status. These findings highlight disitamab vedotin as a promising component of combination regimens for treating HER2-positive gynecological malignancies.