Relative Dose Intensity of Trabectedin and Outcome of Advanced L‐Sarcomas
ABSTRACT Background 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. Methods We c...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-08-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.71131 |
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| Summary: | ABSTRACT Background 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. Methods 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. Results 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%. Conclusion This retrospective study does not support a link between high trabectedin RDI and PFS or OS for advanced L‐sarcoma patients. |
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| ISSN: | 2045-7634 |