Trabectedin

Ringwalt E. M, et al. Molecular Therapy: Oncology, 2024, 32(4), 200886.

Trabectedin was experimentally applied to potentiate oncolytic herpes simplex virus (oHSV)-based immunotherapy in both human xenograft and murine syngeneic bone sarcoma models. Mechanistically, trabectedin disrupted the tumor-intrinsic antiviral response, resulting in increased oHSV gene expression within infected human sarcoma cells. In immune-competent murine models, where viral replication was inherently limited, trabectedin administration (via systemic dosing) significantly enhanced therapeutic efficacy by modulating the tumor microenvironment. Flow cytometry revealed reduced infiltration of immunosuppressive CD4⁺ T cells and myeloid-derived suppressor cells, alongside increased granzyme B expression in tumor-infiltrating cytotoxic T lymphocytes and NK cells. The combination treatment induced robust tumor regression, attributed to both enhanced direct virolytic effects and immune-mediated cytotoxicity. These findings demonstrate trabectedin's dual role: sensitizing tumor cells to oncolytic viral infection and augmenting host antitumor immune responses. The synergistic effects observed underscore the translational potential of combining trabectedin with viroimmunotherapy in sarcoma treatment.

Scandurra G, et al. International Journal of Gynecological Cancer, 2025, 101950.

Trabectedin was evaluated as a maintenance monotherapy in the randomized, multicenter phase II TRAMANT study, which targeted patients with partially platinum-sensitive recurrent ovarian cancer (platinum-free interval: 6-12 months). Following an initial response to six cycles of combination therapy with pegylated liposomal doxorubicin (PLD) and trabectedin (TRB), patients were randomized into two arms: continued PLD + TRB combination or TRB monotherapy. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate, and quality-of-life metrics.
Patients in both arms received a median of six cycles of therapy. Trabectedin was administered intravenously at a dose of 1.1 mg/m² over 3 hours every 3 weeks, either as a standalone maintenance regimen or in continued combination with PLD (30 mg/m² on day 1 every 3 weeks). Median PFS was 9.8 months for TRB alone and 16.6 months for the combination arm, while OS was 19.1 vs. 23.8 months, respectively. Toxicity remained manageable, with grade 3-4 events-mainly neutropenia and anemia-observed in 21% (TRB) and 17% (PLD + TRB) of patients. This clinical study highlights the therapeutic potential of trabectedin as a maintenance regimen following initial response, offering a tolerable, non-platinum alternative for managing relapsed ovarian cancer.