Relative Dose Intensity of Trabectedin and Outcome of Advanced L-Sarcomas

Trabectedin, which is approved for advanced soft tissue sarcoma management, has a complex mechanism of action, but can be classified as an alkylating agent. The need to maintain a high relative dose intensity (RDI) is not clearly established in this clinical setting.

We conducted a retrospective study in five expert centers to compare the progression-free survival (PFS) and overall survival (OS) of patients with advanced L-Sarcomas (liposarcomas or leiomyosarcoma) according to the RDI calculated over the first three cycles (RDI < 80% and RDI ≥ 80%). Comparisons of patients' characteristics were done using Chi-2, Fisher exact, and Wilcoxon tests. Associations between PFS/OS and RDI were estimated and tested in Cox models.

Out of 332 patients treated with trabectedin between 09/1999 and 12/2021, 244 have received at least 3 cycles before progression. Among these 244 patients, the median RDI during the first 3 cycles was 83% (range, 48%-106%), the mean RDI was 81% (±14%) and 106 patients had RDI < 80%. An RDI < 80% was more frequently observed in patients treated in a center with a high volume of activity (82/169, 49%, vs. 24/75, 32%, p = 0.02), in patients who had previously received pazopanib (12/18, 67%, vs. 94/225, 42%, p = 0.04), and in patients who experienced grade 3 neutropenia during the first cycle (56/77, 73% vs. 35/127, 28%, p < 0.001). PFS did not significantly differ according to RDI (p = 0.08): HR_{(< 80%/≥ 80%)} = 0.79 (95% CI, 0.61-1.03), median PFS = 8.4 months (7.0-9.3) when RDI < 80% vs. 5.9 months (4.4-6.8) when RDI ≥ 80%. We observed no significant difference in terms of OS (p = 0.53): HR_{(< 80%/≥ 80%)} = 0.92 (95% CI, 0.70-1.20), median OS = 18.2 months (15.6-23.4) when RDI < 80% vs. 15.8 months (13.2-19.7) when RDI ≥ 80%.

This retrospective study does not support a link between high trabectedin RDI and PFS or OS for advanced L-sarcoma patients.