Clinical and biological factors associated with response to immune checkpoint inhibitors in advanced sarcomas: IMPRESARC, a French retrospective multicenter cohort study
Menée en France à partir de données portant sur 272 patients atteints d'un sarcome de stade avancé traité par inhibiteur de point de contrôle immunitaire, cette étude multicentrique identifie des facteurs biologiques ou cliniques associés à la réponse thérapeutique
Background : Immune checkpoint inhibitors (ICIs) in unselected sarcomas yield limited response rates and tumor control. Long-term responders have however been reported, suggesting a critical challenge in refining patient selection, by identifying reliable predictive factors for response.
Methods : The authors conducted a multicenter, retrospective study of patients with advanced sarcomas treated with ICIs in six French reference sarcoma centers. The study assessed efficacy and safety, as well as clinical and biological variables associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Results : A total of 272 patients were included in the analysis. The ORR was 17%, with 16% partial responses and 1% complete responses. Stable disease (SD) occurred in 33% of patients, resulting in a disease control rate of 49%. Median PFS was 2.7 months (95% confidence interval [CI], 2.5–3.4), with 28% of patients showing PFS >6 months and 13% with PFS >12 months. Median OS was 13.5 months (95% CI, 11.0–17.3). The safety profile was consistent with that of clinical trials, with 5% of patients experiencing grade
≥
3 adverse events and 10% discontinuing treatment due to toxicity. Poorer outcomes were associated with high Eastern Cooperative Oncology Group performance status (
≥
1), cyclophosphamide coadministration, and high derived neutrophil-to-lymphocyte ratio. Anti-programmed death-ligand 1 (PD-L1) therapies were associated with shorter OS compared to anti–PD-1. Histotypes such as alveolar soft part sarcoma (ASPS) had better survival, whereas dedifferentiated liposarcoma had poorer outcomes.
Conclusions : Despite a short median PFS, certain histological subtypes, including ASPS, chordomas, SMARCA4-deficient tumors, gastro-intestinal stromal tumor, and NF1 mutations, showed strong activity signals, indicating long-term responses in some patients.
Cancer , article en libre accès, 2025