Immunotherapy and Targeted Therapies in Sarcoma: Proposed Synergy with Combination Treatment
Aleksandra Watson1, Gina D'Amato2, Emily Jonczak2
1Department of Pharmacy, Sylvester Comprehensive Cancer Center/University of Miami, Miami, FL, USA.
Abstract:
The combination of targeted therapies and immunotherapies for advanced and metastatic sarcomas has been proposed owing to the enhanced effect of antiangiogenic therapies on the tumor microenvironment. We found eight studies published to date assessing the effectiveness of combined multitargeted vascular endothelial growth factor (VEGF)-tyrosine kinase inhibitors with immune checkpoint inhibitors (ICIs) in sarcoma. It is difficult to draw conclusions owing to limited data and primarily single-arm studies, although initial literature appears promising and requires further study. It remains unknown which sarcoma subtypes may derive the most benefit owing to the limited literature. Benefit was seen primarily in angiosarcoma (AS) and alveolar soft part sarcoma (ASPS), as well as in other tumor subtypes, with few patients achieving complete response (CR). The patients who achieved CRs had desmoplastic small round cell tumor (DSRCT), AS, and chondrosarcoma (CS). Mixed results were found in patients with leiomyosarcoma (LMS), gastrointestinal stromal tumor (GIST), and bone sarcomas, although combination therapy appears to be less effective in these subtypes. Further studies are required to explore optimal treatment agents and dosing strategies to improve both efficacy and tolerability. Although initial results are promising in select patients, phase 3 randomized controlled trials are necessary to determine true treatment effect with combination therapy versus VEGF-inhibitor or ICI alone.
Insights
Combining targeted therapies with immunotherapy shows promise for advanced sarcomas, particularly angiosarcoma. However, limited data necessitates further research to determine optimal strategies and identify which sarcoma subtypes benefit most.
Area of Science:
- Oncology
- Cancer Research
- Immunotherapy
Background:
- Advanced and metastatic sarcomas present treatment challenges.
- Antiangiogenic therapies can modify the tumor microenvironment.
- Combination therapy of targeted agents and immunotherapy is a proposed strategy.
Purpose of the Study:
- To assess the effectiveness of combined multitargeted vascular endothelial growth factor (VEGF)-tyrosine kinase inhibitors with immune checkpoint inhibitors (ICIs) in sarcoma.
- To identify sarcoma subtypes that may benefit from this combination therapy.
Main Methods:
- Systematic review of eight studies evaluating combined VEGF-tyrosine kinase inhibitors and ICIs in sarcoma.
- Analysis of treatment outcomes, including complete response (CR), across different sarcoma subtypes.
Main Results:
- Limited data from primarily single-arm studies hinders definitive conclusions.
- Initial results appear promising in select subtypes like angiosarcoma (AS) and alveolar soft part sarcoma (ASPS).
- Complete responses were observed in desmoplastic small round cell tumor (DSRCT), AS, and chondrosarcoma (CS).
- Mixed or less effective results were noted in leiomyosarcoma (LMS), gastrointestinal stromal tumor (GIST), and bone sarcomas.
Conclusions:
- Combination therapy shows potential benefit in specific sarcoma subtypes but requires further investigation.
- Optimal treatment agents, dosing, and patient selection need exploration.
- Phase 3 randomized controlled trials are essential to establish the true efficacy of combination therapy versus monotherapy.
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