Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma
Background and objectives: Dimensional response is an unmet need in second lines of advanced soft tissue sarcomas (STS). Indeed, the three approved drugs, pazopanib, trabectedin, and eribulin, achieved an overall response rate (ORR) of less than 10%. This fact potentially hinders the options for fas...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2024-01-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359231225044 |
| _version_ | 1797341258031562752 |
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| author | Javier Martin-Broto Alicia Olarte-García Ricardo Fernandéz-Rodríguez Marta Ribeiro Ferreira Irene Carrasco-García Fernando Galvez-Montosa Inmaculada Rincon-Perez Javier Peinado-Serrano Ignacio Azinovic Laura Guzman-Gomez Lurdes Salgado Alberto Sevillano Justo Ortega Cristina Alvarez Antonio Gutierrez David S. Moura Nadia Hindi |
| author_facet | Javier Martin-Broto Alicia Olarte-García Ricardo Fernandéz-Rodríguez Marta Ribeiro Ferreira Irene Carrasco-García Fernando Galvez-Montosa Inmaculada Rincon-Perez Javier Peinado-Serrano Ignacio Azinovic Laura Guzman-Gomez Lurdes Salgado Alberto Sevillano Justo Ortega Cristina Alvarez Antonio Gutierrez David S. Moura Nadia Hindi |
| author_sort | Javier Martin-Broto |
| collection | DOAJ |
| description | Background and objectives: Dimensional response is an unmet need in second lines of advanced soft tissue sarcomas (STS). Indeed, the three approved drugs, pazopanib, trabectedin, and eribulin, achieved an overall response rate (ORR) of less than 10%. This fact potentially hinders the options for fast symptomatic relief or surgical rescue. The combination of trabectedin plus low-dose radiation therapy (T-XRT) demonstrated a response rate of 60% in phase I/II trial, while real-life data achieved 32.5% ORR, probably due to a more relaxed timing between treatments. These results were obtained in progressing and advanced STS. In this study, the merged databases (trial plus real life) have been analyzed, with a special focus on leiomyosarcoma patients. Design and methods: As responses were seen in a wide range of sarcoma histologies (11), this study planned to analyze whether leiomyosarcoma, the largest subtype with 26 cases (30.6%) in this series, exhibited a better clinical outcome with this therapeutic strategy. In addition, four advanced and progressing leiomyosarcoma patients, all with extraordinarily long progression-free survival of over 18 months, were collected. Results: A total of 847 cycles of trabectedin were administered to 85 patients, with the median number of cycles per patient being 7 (1–45+). A trend toward a longer progression-free survival (PFS) was observed in leiomyosarcoma patients with median PFS (mPFS) of 9.9 months [95% confidence interval (CI): 1.1–18.7] versus 5.6 months (95% CI: 3.2–7.9) for the remaining histologies, p = 0.25. When leiomyosarcoma and liposarcoma were grouped, this difference reached statistical significance, probably due to the special sensitivity of myxoid liposarcoma. The mPFS for L-sarcomas was 12.7 months (95% CI: 7–18.5) versus 4.3 months (95% CI: 3.3–5.3) for the remaining histologies, p = 0.001. Cases with long-lasting disease control are detected among leiomyosarcoma patients. Conclusion: Even when extraordinarily long-lasting responses do exist among leiomyosarcoma patients treated with T-XR, we were unable to demonstrate a significant difference favoring leiomyosarcoma patients in clinical outcomes. |
| first_indexed | 2024-03-08T10:15:19Z |
| format | Article |
| id | doaj.art-1475ef79f82c4873859ed0806a878ff3 |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-03-08T10:15:19Z |
| publishDate | 2024-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-1475ef79f82c4873859ed0806a878ff32024-01-28T18:05:57ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592024-01-011610.1177/17588359231225044Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcomaJavier Martin-BrotoAlicia Olarte-GarcíaRicardo Fernandéz-RodríguezMarta Ribeiro FerreiraIrene Carrasco-GarcíaFernando Galvez-MontosaInmaculada Rincon-PerezJavier Peinado-SerranoIgnacio AzinovicLaura Guzman-GomezLurdes SalgadoAlberto SevillanoJusto OrtegaCristina AlvarezAntonio GutierrezDavid S. MouraNadia HindiBackground and objectives: Dimensional response is an unmet need in second lines of advanced soft tissue sarcomas (STS). Indeed, the three approved drugs, pazopanib, trabectedin, and eribulin, achieved an overall response rate (ORR) of less than 10%. This fact potentially hinders the options for fast symptomatic relief or surgical rescue. The combination of trabectedin plus low-dose radiation therapy (T-XRT) demonstrated a response rate of 60% in phase I/II trial, while real-life data achieved 32.5% ORR, probably due to a more relaxed timing between treatments. These results were obtained in progressing and advanced STS. In this study, the merged databases (trial plus real life) have been analyzed, with a special focus on leiomyosarcoma patients. Design and methods: As responses were seen in a wide range of sarcoma histologies (11), this study planned to analyze whether leiomyosarcoma, the largest subtype with 26 cases (30.6%) in this series, exhibited a better clinical outcome with this therapeutic strategy. In addition, four advanced and progressing leiomyosarcoma patients, all with extraordinarily long progression-free survival of over 18 months, were collected. Results: A total of 847 cycles of trabectedin were administered to 85 patients, with the median number of cycles per patient being 7 (1–45+). A trend toward a longer progression-free survival (PFS) was observed in leiomyosarcoma patients with median PFS (mPFS) of 9.9 months [95% confidence interval (CI): 1.1–18.7] versus 5.6 months (95% CI: 3.2–7.9) for the remaining histologies, p = 0.25. When leiomyosarcoma and liposarcoma were grouped, this difference reached statistical significance, probably due to the special sensitivity of myxoid liposarcoma. The mPFS for L-sarcomas was 12.7 months (95% CI: 7–18.5) versus 4.3 months (95% CI: 3.3–5.3) for the remaining histologies, p = 0.001. Cases with long-lasting disease control are detected among leiomyosarcoma patients. Conclusion: Even when extraordinarily long-lasting responses do exist among leiomyosarcoma patients treated with T-XR, we were unable to demonstrate a significant difference favoring leiomyosarcoma patients in clinical outcomes.https://doi.org/10.1177/17588359231225044 |
| spellingShingle | Javier Martin-Broto Alicia Olarte-García Ricardo Fernandéz-Rodríguez Marta Ribeiro Ferreira Irene Carrasco-García Fernando Galvez-Montosa Inmaculada Rincon-Perez Javier Peinado-Serrano Ignacio Azinovic Laura Guzman-Gomez Lurdes Salgado Alberto Sevillano Justo Ortega Cristina Alvarez Antonio Gutierrez David S. Moura Nadia Hindi Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma Therapeutic Advances in Medical Oncology |
| title | Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma |
| title_full | Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma |
| title_fullStr | Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma |
| title_full_unstemmed | Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma |
| title_short | Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma |
| title_sort | trabectedin and low dose radiation therapy in patients with advanced leiomyosarcoma |
| url | https://doi.org/10.1177/17588359231225044 |
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