Trabectedin 250microgram powder for solution for infusion vials

Background: Leiomyosarcomas are an aggressive soft-tissue sarcoma that arise from smooth muscle, have a high metastatic potential and account for 10-20% of soft-tissue sarcomas. Despite decades of research, the first-line treatment remains unresolved due to the absence of direct comparative trials, heterogeneous study designs, and trade-offs between efficacy and toxicity. This systematic review evaluates the optimal therapeutic systemic chemotherapy regimens in the first-line setting, specifically gemcitabine- and doxorubicin-based regimens, including associated toxicities. Methods: A systematic search in MEDLINE (Ovid), Embase (Ovid), and Cochrane Library (Wiley) identified studies of first-line gemcitabine- or doxorubicin-based chemotherapy for leiomyosarcoma. The review protocol was registered in PROSPERO (CRD420261280028). Of the 3092 articles screened, 11 articles were eligible for inclusion, comprising results from 1225 patients. Eligible studies were in English and included ≥10 patients with advanced/metastatic leiomyosarcoma reporting on LMS-specific outcomes and no prior systemic therapy. This qualitative systematic review synthesizes prospective and retrospective evidence without quantitative meta-analysis. Results: The review included two phase 3 trials, six phase 2 trials, one phase 1b trial, and two retrospective studies. While there was no direct comparison in this setting, doxorubicin-based combinations consistently reported higher objective response rates, progression-free survival, and overall survival. The most favorable outcomes were observed in the LMS04 trial with doxorubicin plus trabectedin followed by surgery and trabectedin maintenance, yielding a median progression-free survival of 12 months, overall survival of 33 months, and objective response rate of 36%. This regimen also had the highest grade 3-4 toxicity. Conclusions: Doxorubicin-based regimens remain the most active first-line option for leiomyosarcoma, although treatment practices remain heterogeneous.

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ABSTRACT Introduction Soft tissue sarcomas (STS) are rare malignancies with diverse histological subtypes and an incidence of approximately 40 cases per million annually. Although several agents, including pazopanib, trabectedin, and eribulin, have been approved in Japan since 2012 for patients previously treated with anthracyclines, clinical guidelines provide no consistent recommendations regarding second-line regimens. Given the lack of head-to-head evidence, treatment selection largely depends on clinician discretion. This study aims to evaluate the comparative efficacy of second-line or later pharmacological regimens for unresectable, advanced, or recurrent STS through a systematic review and network meta-analysis (NMA). Methods and analysis Randomized controlled trials (RCTs), including multi-arm designs, will be identified through comprehensive searches of MEDLINE (via PubMed), Embase (via ProQuest), CENTRAL, WHO ICTRP, and ClinicalTrials.gov from inception to the search date, without language restrictions. Two reviewers will independently screen records, extract data, and assess risk of bias using the Cochrane RoB 2 tool; discrepancies will be resolved by a third reviewer. Pairwise meta-analyses will be performed using random-effects models, followed by a frequentist NMA with between-study variance estimated by REML. Consistency will be assessed using design-by-treatment interaction models (global) and node-splitting methods (local). Treatment ranking will be evaluated using P-scores or SUCRA. Certainty of evidence for each outcome will be assessed using CINeMA in line with the GRADE framework. Support/ Funding This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. Ethics and dissemination This systematic review and network meta-analysis will be conducted using data extracted from previously published studies and trial registries. As no individual patient data will be collected or used, ethical approval is not required.The findings of this review will be disseminated through publication in a peer-reviewed journal and presentation at relevant scientific conferences. The results will also be shared with clinicians, policymakers, and researchers to inform clinical practice and future research. The final dataset and analytic code may be made available in an open-access repository to ensure transparency and reproducibility. PROSPERO Registration number CRD420251156600

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The Korean Society of Gynecologic Oncology has updated its clinical practice guidelines for endometrial cancer to incorporate advancements in recent high-quality randomized controlled trials. These guidelines address evolving treatment paradigms, and are tailored to the Korean medical context. Key updates include a strong recommendation for doxorubicin/trabectedin combination therapy in metastatic or recurrent unresectable leiomyosarcoma based on the significant survival benefits demonstrated in a randomized controlled trial. For advanced or recurrent endometrial cancer, immune checkpoint inhibitors combined with chemotherapy have received strong recommendations, owing to their proven efficacy and increased accessibility in Korea. Conditional recommendations were made for combination therapies involving durvalumab and olaparib, reflecting their potential benefits, but acknowledging regulatory and accessibility constraints. These guidelines aim to provide evidence-based, practical strategies to optimize care for patients with endometrial cancer while addressing unmet clinical needs and adapting global advancements to Korea's healthcare environment.

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