Aims: Therapeutic options after trabectedin in advanced L-sarcomas are poorly defined, and real-world evidence on sequencing, efficacy and safety is limited. We aimed to characterise post-trabectedin systemic therapy and outcomes in the multicentre SEPSaC-01 cohort.
Methods: We retrospectively analysed all 139 eligible patients with advanced liposarcoma or leiomyosarcoma treated with trabectedin; no formal sample size target was prespecified. Treatment patterns and outcomes were assessed in 83 patients who received subsequent systemic therapy. Progression-free survival (PFS), overall survival (OS), treatment exposure, dose modifications, discontinuation and adverse events (AEs) were evaluated. Survival curves were compared using the log-rank test and categorical variables using chi-squared or Fisher’s exact tests.
Results: Of 139 patients, 83 (59.7%) received subsequent therapy, 51 (36.7%) did not and 5 (3.6%) remained on trabectedin. PFS and OS were evaluable in 69 and 48 patients, respectively, owing to missing event dates. Pazopanib (32.5%) and docetaxel plus gemcitabine (25.3%) were the most common first post-trabectedin regimens; 45/83 patients (54.2%) received a second post-trabectedin line. Median PFS was 4.3 months; 6-, 12- and 18-month PFS rates were 38.3%, 9.0% and 4.5%. Median OS was 12.5 months; 6-, 12- and 18-month OS rates were 78.3%, 51.4% and 36.0%. PFS did not differ significantly among pazopanib, docetaxel plus gemcitabine and other regimens (p=0.825). Median treatment exposure was 3 cycles (IQR 2–6; n=80). Dose reductions and delays occurred in 19.3% and 10.8%, respectively. Progression was the main reason for discontinuation (57.8%). AEs occurred in 38.6%, most commonly haematological AEs (26.5%).
Conclusions: Nearly 60% of patients received systemic therapy after trabectedin, and 54.2% of these patients received a second post-trabectedin line. Treatment was heterogeneous and outcomes were modest. No significant PFS differences were detected between regimen groups, highlighting the need for prospective studies to define optimal treatment sequencing in advanced L-sarcomas.