Outcomes of immunotherapy in advanced osteosarcoma patients: A systematic review and meta-analysis.

Abstract

e23515 Background: Osteosarcoma is the most commonly diagnosed primary bone tumor. Advanced or metastatic osteosarcoma is a very aggressive tumor with poor survival outcomes. This study aims to explore outcomes of immunotherapy in advanced osteosarcoma patients. Methods: A systematic search was conducted on PubMed, Cochrane, and Clinicaltrials.gov following PRISMA guidelines, and twelve studies reporting outcomes of immunotherapy in osteosarcoma were included after screening 419 studies. Inter-study variance was assessed using the Der Simonian-Laird Estimator, and pooled analysis was conducted with 95% confidence intervals using the ‘meta’ package in R (version 4.16-2). Results: 349 patients from twelve studies (2015-2024) were included for analysis. The median age was 21.5 (11-84) years and the majority (65%, n = 223/343) were male. 42% (n = 5) studies were prospective, 33% (n = 4) were phase I/II trials, and 17% (n = 2) were retrospective. The majority of patients (94%, n = 158/169) had metastatic osteosarcoma and the most common site was femur and tibia (66%, n = 192/292). Tumor size was characterized as ≥5 cm (70%, n = 112/160) and < 5 cm (30%, n = 48). ECOG performance status was 0 (66%, n = 126/190) and 1 (34%, n = 64/190). The most commonly used immunotherapies included tumor-infiltrating lymphocytes (TIL) monotherapy or in combination with nivolumab (46%, n = 160) and Camrelizumab (32%, n = 111). The prior number of chemotherapy lines was 2 (1-4). Median follow-up was 18.9 (1.1-61.1) months. The pooled rates of overall response (OR), complete response (CR), and partial response (PR) were 11.5% (95% CI 7.6-16, I 2 = 89%, p < 0.01, n = 264), 0.1% (95% CI 0.0-1.5, I 2 = 0%, p = 0.72, n = 291), and 9% (95% CI 5.6-13, I 2 = 85%, p < 0.01, n = 291), respectively. The pooled rates of stable disease (SD), progressive disease (PD), and disease control rate (DCR) were 54.7% (95% CI 46.8-62.5, I 2 = 95%, p < 0.01, n = 171), 36.9% (95% CI 29.4-44.7, I 2 = 95%, p < 0.01, n = 171), and 79.1% (95% CI 72.9-84.9, I 2 = 89%, p < 0.01, n = 202), respectively. At 6 and 12 months, the pooled overall survival (OS) was 91.8% (95% CI 88.2-94.9, I 2 = 87%, p < 0.01, n = 313) and 68.9% (95% CI 63.5-74.1, I 2 = 96%, p < 0.01, n = 313), respectively. At 6 and 12 months, the pooled progression-free survival (PFS) was 63.5% (95% CI 57.1-69.6, I 2 = 94%, p < 0.01, n = 248) and 36.4% (95% CI 29.7-43.4, I 2 = 96%, p < 0.01, n = 207), respectively. The pooled rate of grade III/IV adverse events (AE) was 40.5% (95% CI 33.2-48, I 2 = 97%, p < 0.01, n = 177). Conclusions: This meta-analysis shows promising results for immunotherapy in osteosarcoma treatment and highlights the need for prospective trials with larger patient populations to understand immunotherapy outcomes in osteosarcoma better.