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Updated: Jun 26, 2025
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
Combination treatment with PD1/PDL-1 inhibitors for sarcomas: state of the art, next questions
Javier Martin-Broto1,2,3, Nadia Hindi1,2,3, David S Moura3
1Medical Oncology Department, Fundación Jimenez Diaz University Hospital.
Purpose Of Review:
Only a small fraction of sarcomas exhibit recognized parameters of immune sensitivity, such as tumor mutational burden, PDL-1 expression, or microsatellite instability. Combined strategies aimed to modulate tumor microenvironment to increase the efficacy of PD1/PDL-1 inhibitors in sarcoma. Most explored prospective studies were based on combinations of PD1/PDL-1 inhibitors with antiangiogenics, other immune checkpoints, or chemotherapy.
Recent Findings:
Results on 6-month PFS rate, median PFS, and ORR in trials using PD1/PDL-1 inhibitors plus antiangiogenics ranged respectively as 46.9-55%, 4.7-7.8 months and 21-36.7%. In combination with other immune checkpoint inhibitors, the results of median PFS and ORR ranged from 2.8-4.1 months and 10-16%, respectively. In combination with chemotherapy, the best results were obtained with doxorubicin-based regimens compared to other agents. Duplet-based chemotherapy plus anti-PD1/PDL-1 obtained the highest ORR (56.2%) compared with doxorubicin (19-36.7%). Currently, the most robust predictive biomarker for anti-PD1/PDL-1 efficacy is the presence of tertiary lymphoid structures (TLS) with mature dendritic cells.
Summary:
Even when direct comparisons between PD1/PDL-1 inhibitor-based combinations and single agents have not been performed yet in sarcoma, some combinations appear promising. Studies controlling heterogeneity by biomarker or histotype selection contribute to an increase in efficacy or knowledge crucial for future comparative trials.
Insights
Immune checkpoint inhibitors combined with antiangiogenics, chemotherapy, or other immune checkpoints show promise for sarcoma treatment. Tertiary lymphoid structures are a key biomarker for predicting response to PD1/PDL-1 inhibitors.
Area of Science:
- Oncology
- Immunotherapy
- Sarcoma Research
Background:
- Sarcomas rarely exhibit intrinsic immune sensitivity markers.
- Combined immunotherapies aim to enhance PD1/PDL-1 inhibitor efficacy by modulating the tumor microenvironment.
- Previous studies explored combinations of PD1/PDL-1 inhibitors with antiangiogenics, other immune checkpoints, or chemotherapy.
Purpose of the Study:
- To review current strategies combining PD1/PDL-1 inhibitors with other agents for sarcoma treatment.
- To assess the efficacy of these combination therapies based on available trial data.
- To identify predictive biomarkers for response to PD1/PDL-1 inhibitors in sarcoma.
Main Methods:
- Review of prospective studies on PD1/PDL-1 inhibitor combinations in sarcoma.
- Analysis of efficacy data including progression-free survival (PFS) and objective response rate (ORR).
- Evaluation of predictive biomarkers such as tertiary lymphoid structures (TLS).
Main Results:
- PD1/PDL-1 inhibitors plus antiangiogenics showed 6-month PFS rates of 46.9-55% and median PFS of 4.7-7.8 months.
- Combinations with other immune checkpoint inhibitors yielded median PFS of 2.8-4.1 months and ORR of 10-16%.
- Duplet chemotherapy combined with anti-PD1/PDL-1 achieved the highest ORR (56.2%). Tertiary lymphoid structures with mature dendritic cells emerged as a robust predictive biomarker.
Conclusions:
- Certain PD1/PDL-1 inhibitor combinations show promise in sarcoma, though direct comparisons with single agents are lacking.
- Biomarker-driven or histotype-selected studies are crucial for increasing efficacy and informing future trials.
- Further research is needed to optimize combination strategies and identify patient populations most likely to benefit from these treatments.
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