(P 232) IMMUNE CHECKPOINT INHIBITORS COMBINED WITH TYROSINE KINASE INHIBITORS FOR SOFT-TISSUE SARCOMAS: A SYSTEMATIC REVIEW AND SINGLE-ARM META-ANALYSIS

Objective: Soft-tissue sarcomas (STS) are uncommon cancers, comprising about 1% of adult malignancies. The prognosis for metastatic STS is generally poor, despite numerous attempts to enhance outcomes for advanced cases, which have largely been unsuccessful. Although immune checkpoint inhibitors combined with tyrosine kinase inhibitors have improved outcomes for other tumor types, the effectiveness of these combinations for STS is still controversial. Therefore, we performed a systematic review and meta-analysis evaluating specifically the combination immune checkpoint inhibitors with tyrosine kinase inhibitors in STS.

Methods: PubMed, EMBASE, and Cochrane databases were searched for prospective trials that evaluated the efficacy and the toxicity of combinations of immune checkpoint inhibitors with tyrosine kinase inhibitors for the treatment of advanced STS. The primary outcomes of interest were overall response rate (ORR), progression-free survival (PFS), and adverse events grade 3 or more. A sub-analysis was performed to evaluate the efficacy of the combination for alveolar soft-part sarcomas. The random-effect model was used for statistical analysis.

Results: We identified 8 prospective phase II trials, including 332 patients with multiple histologic subtypes of STS. The median age was 45 years (19-72). The pooled ORR was 33.1% (95% CI:17%-49%, P< 0.001, I² =93.5%), median PFS was 7.07 months (95% CI: 5.50-8.64, P< 0.001, I²=81.88%). A subgroup analysis was performed to evaluate the efficacy of the combination for patients for 79 patients with alveolar soft parts sarcoma, the pooled ORR for this population was 73.6% (95% CI: 64%-82%, P=0.531, I² =0). The incidence of adverse events grade 3 or higher was 39.9% (95% CI: 31%-48%, P=0.935, I²= 0).

Conclusion: This study suggests the potential efficacy of combining immune checkpoint inhibitors with tyrosine kinase inhibitors, particularly for alveolar soft-part sarcoma. About one-third of patients experienced adverse events grade 3 or more. Further research, particularly using biomarkers, is required to enhance patient selection and treatment outcomes.