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Following the advancement of immunotherapy (IO) in other cancers, there is heightened interest in exploring its role in soft tissue sarcoma (STS). Immune checkpoint inhibitors (ICIs) have been investigated either as monotherapy or in combinations in small phase 2 clinical trials including various STS histotypes. Their results were modest, with the exception of alveolar soft part sarcoma (ASPS). We aimed to assess the real-world clinical outcomes and safety of ICIs in Greek STS patients. Medical records from STS patients treated with off-label ICIs (as monotherapy or in combinations) from 2020 to 2023 at 8 centers within the Hellenic Group of Sarcoma and Rare Cancers were retrospectively reviewed. End-points were progression-free survival (PFS), overall survival (OS) and safety. In total, 25 patients with metastatic STS were identified (median age 62 years, range 23-85). Patients had received 0-6 (median 2) prior treatment lines for advanced disease. Biomarkers related to IO were available for 12 patients: PDL1 expression in immune cells was positive (low) in 2/8, tumor mutational burden (TMB) was high in 2/9 and microsatellite instability (MSI) was high in 1/11 tested tumors. Nine patients exhibited partial response as best response (36% response rate), with the following histotypes: 2 leiomyosarcomas, 2 undifferentiated pleomorphic sarcomas, 1 ASPS, 1 myxofibrosarcoma, 1 dedifferentiated liposarcoma, 1 pleomorphic dermal sarcoma and 1 malignant granular cell tumor. Among the responders, only two expressed a biomarker of IO (one high TMB and another one MSI-high). Median PFS was 4.5 months (0.9-30.6) and median OS 9 months (1.7-34). Four patients experienced prolonged PFS (>12 months). IO regimens were well tolerated, with mainly grade 1-2 adverse events (colitis, anorexia, thyroid disorders, fatigue, skin toxicity), none of which led to treatment discontinuation. With the limitation of a small sample size and a retrospective study design, this analysis shows that ICIs benefit a subset of STS patients. Prospective studies are needed to identify the optimal patient population. A histology-driven approach, coupled with the establishment of novel IO biomarkers, is warranted.
Kokkali-Zervos et al. (Fri,) studied this question.