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. 2024 Jan 27:16:17588359231225044.
doi: 10.1177/17588359231225044. eCollection 2024.

Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma

Javier Martin-Broto  1   2   3 , Alicia Olarte-García  4 , Ricardo Fernandéz-Rodríguez  5 , Marta Ribeiro Ferreira  6 , Irene Carrasco-García  7 , Fernando Galvez-Montosa  8 , Inmaculada Rincon-Perez  9 , Javier Peinado-Serrano  9   10   11 , Ignacio Azinovic  12 , Laura Guzman-Gomez  12 , Lurdes Salgado  13 , Alberto Sevillano  14   2   3 , Justo Ortega  14   2   3 , Cristina Alvarez  15 , Antonio Gutierrez  16 , David S Moura  3 , Nadia Hindi  14   2   3
Affiliations

Trabectedin and low-dose radiation therapy in patients with advanced leiomyosarcoma

Javier Martin-Broto et al. Ther Adv Med Oncol. .

Abstract

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.

Keywords: durable response; leiomyosarcoma; soft tissue sarcomas; trabectedin.

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Conflict of interest statement

JM-B reports research grants from PharmaMar, Eisai, Immix BioPharma, and Novartis outside the submitted work; honoraria for advisory board participation and expert testimony from PharmaMar, Eli Lilly and Company, Bayer, GSK, Novartis, Boehringer Ingelheim, Amgen, Roche, Tecnofarma, and Asofarma; and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, BMS, Pfizer, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Celgene, Novartis, Blueprint, Adaptimmune, Nektar, Forma, Amgen, Daiichi-Sankyo, Ran Therapeutics, INHIBRX, Ayala Pharmaceuticals, Philogen, Cebiotex, PTC Therapeutics, Inc., and SpringWorks therapeutics. DSM reports institutional research grants from PharmaMar, Eisai, Immix BioPharma, and Novartis outside the submitted work; travel support from PharmaMar, Eisai, Celgene, Bayer, and Pfizer; and personal fees from Tecnopharma, outside the submitted work. NH reports grants, personal fees and non-financial support from PharmaMar, personal fees from Lilly and Tecnopharma, grants from Eisai, and Novartis, outside the submitted work and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint, Nektar, Forma, Amgen, and Daiichi-Sankyo. The remaining authors declare no competing interests.

Figures

Figure 1.
Figure 1.
Survival analysis. Kaplan–Meier curves for (a) PFS between L-sarcomas and non-L-sarcomas and (b) OS between L-sarcomas and non-L-sarcomas. OS, overall survival; PFS, progression-free survival.
Figure 2.
Figure 2.
Case report #1. (a) LUL nodule-irradiated nodule. From left to right: baseline PET/CT scan in February 2021. CT imaging previous to cycle 9 of trabectedin and radiotherapy (August 2021). CT straight after the 11th cycle of trabectedin and concomitant radiotherapy, already showing a reduction in the LUL nodule. CT in September 2022 after the 18th cycle of trabectedin showed a maintained partial response. (b) Evolution of the nodule in URL, showing partial response to therapy. (c) Evolution of paravertebral nodule (above) and hepatorenal space implant (below). CT, computerized tomography; PET, positron emission tomography; LUL, left upper lobe; URL, upper right lobe.
Figure 3.
Figure 3.
Case reports #2, #3, and #4. Pelvic CT scan of case report #2: (a) right paramedian retrovesical pelvic mass, 7.0 × 6.1 × 8.8 cm, in July 2019 and (b) pelvic mass, 3.7 × 4.7 cm, after trabectedin and radiotherapy to pelvic mass, followed by 31 cycles of trabectedin, in October 2021. CT scan of case report #3: (c) at baseline and (d) showing stable disease after three cycles. Density change was achieved. Axial MRI of case report #4: (e) at baseline and (f) best response. The response (f) was achieved and maintained, without the need for further treatment. CT, computerized tomography; MRI, magnetic resonance imaging.
See this image and copyright information in PMC

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