PURPOSE Next-generation sequencing (NGS) provides an opportunity to leverage genomic data to identify novel factors associated with treatment outcomes. We examined outcomes of systemic therapy in patients with soft tissue (nonuterine) leiomyosarcoma (LMS) who had NGS at our center to identify associations of those NGS findings with radiologic outcomes. METHODS We reviewed 168 patients with soft tissue LMS who received systemic therapy between 2009 and 2024 for metastatic LMS and also had Memorial Sloan-Kettering Integrated Mutation Profiling of Actionable Cancer Targets profiling. We conducted univariate and multivariate Cox regression analyses of clinicopathologic factors and genomic alterations for progression-free survival (PFS) for first- and second-line systemic therapy. RESULTS There were 110 female and 58 male patients in this cohort. Patients received 1-12 lines of systemic therapy for metastatic disease. Treatment regimens were categorized as (1) doxorubicin-based, (2) pegylated liposomal doxorubicin (PLD)–based, (3) gemcitabine-based, (4) pazopanib, and (5) other. On univariate analysis, inferior PFS for first-line chemotherapy was associated with high mitotic activity, necrosis, and TP53 or RB1 mutation. On multivariate analysis, only the therapeutic class was associated with PFS, with statistically inferior outcomes for PLD-containing combinations across the full cohort. Tumor size >10 cm, high mitotic rate, and TP53 alterations were associated with inferior PFS in the PLD-based treatment subgroup. High mitotic rate was associated with inferior PFS in the gemcitabine-based treatment subgroup. CONCLUSION Both doxorubicin- and gemcitabine-based therapy showed significantly greater activity than PLD-based therapy. NGS results were not predictive for outcomes with first- or second-line treatment for metastatic soft tissue LMS. These data may merit re-examination when data are accumulated regarding the increasing use of doxorubicin-trabectedin in this population.
Dermawan et al. (Sun,) studied this question.