(P 247) THE REAL-WORLD EFFICACY OF IMMUNE CHECKPOINT INHIBITORS WITH CONCURRENT RADIATION OR SURGERY IN MULTIMODAL TREATMENT OF SOFT TISSUE SARCOMAS: A RETROSPECTIVE STUDY

Objective: Previous research has demonstrated the effectiveness of immune checkpoint inhibitors (ICIs) across various sarcoma subtypes. However, the rarity of these diseases means that there is still much to learn about the use of ICIs in specific sarcoma subtypes and their use along with adjuvant treatment. Patients are frequently treated with ICIs as part of clinical trials, resulting in a lack of real-world data from the academic community settings. This study aims to provide insights into the real-world efficacy of ICIs in soft tissue sarcomas (STS) based on current clinical practice and decision making.

Methods: A retrospective cohort review was conducted at Kellogg Cancer Center at Endeavor Health to identify patients with STS who received ICI between 2016 and 2023. Patients who participated in clinical trials involving ICI were excluded from this review. Logistic and Cox regression models were utilized to assess the impact of patient characteristics, previous treatments, and baseline factors on outcomes including complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), according to the Response Evaluation Criteria in Solid Tumors (RECIST). A Z-test statistic was utilized to compare patients who were treated with ICI alone in comparison to patients who were treated with ICI with concurrent radiation or surgery.

Results: We identified 29 patients with STS who received pembrolizumab (n=23), nivolumab (n=5), and a combination of ipilimumab/nivolumab (n=1). Among these patients, CR was achieved in 3 individuals diagnosed with undifferentiated pleomorphic sarcoma (UPS), 1 with SMARCA4 deficient undifferentiated sarcoma and 1 with dedifferentiated chondrosarcoma. Of those who achieved CR, 2 received pembrolizumab alone, 1 received pembrolizumab with concurrent radiation therapy, 1 received nivolumab with concurrent resection of the brain metastatic disease and amputation for resistant extremity primary, and 1 received pembrolizumab with concurrent Mohs surgery. Additionally, PR was reported in 4 patients, including 1 with UPS who received pembrolizumab alone, 1 with spindle cell sarcoma of bone who received pembrolizumab with concurrent radiation therapy, 1 with dedifferentiated liposarcoma who received pembrolizumab with concurrent radiation therapy, and 1 with malignant peripheral nerve sheath tumor who received ipilimumab/nivolumab with concurrent radiation therapy.
Among the 23 patients who received immune checkpoint inhibitors (ICI) alone without concurrent radiation or surgery, 3 achieved a durable response (complete response or partial response). In contrast, all 6 patients who received ICI with concurrent radiation or surgery achieved a durable response. Patients who received concurrent radiation or surgery were significantly more likely to experience a durable response compared to those who received ICI alone (p = 0.000041).
Treatment was completed in 6 patients (20.7%). Treatment discontinuation occurred in 23 patients due to disease progression (n=18), toxicities (n=3), and death (n=2). The median progression-free survival (PFS) was 4.87 months, and the median overall survival was 40 months.

Conclusion: This study provides further evidence of the real-world efficacy of ICI in various sarcoma subtypes. The observed rates of CR and PR were high, and the responses were durable, though selection bias for treatment may have influenced these outcomes. The data supports the use of ICI to treat select metastatic sarcoma, particularly when combined with radiation therapy or surgery, across different subtypes.