Mina Fazel MD, Romain Varnier MD, Hélène Vanacker MD, PhD, Nicolas Penel MD, PhD, Sarah Watson MD, PhD, Benjamin Verret MD, Thibaud Valentin MD, Emmanuelle Bompas MD, Waisse Waissi MD, PhD, Alexandra Meurgey MD, Françoise Ducimetière PhD, Jean-Yves Blay MD, PhD, Armelle Dufresne MD, PhD, Mehdi Brahmi MD, PhD
{"title":"与晚期肉瘤免疫检查点抑制剂应答相关的临床和生物学因素：IMPRESARC，一项法国回顾性多中心队列研究","authors":"Mina Fazel MD, Romain Varnier MD, Hélène Vanacker MD, PhD, Nicolas Penel MD, PhD, Sarah Watson MD, PhD, Benjamin Verret MD, Thibaud Valentin MD, Emmanuelle Bompas MD, Waisse Waissi MD, PhD, Alexandra Meurgey MD, Françoise Ducimetière PhD, Jean-Yves Blay MD, PhD, Armelle Dufresne MD, PhD, Mehdi Brahmi MD, PhD","doi":"10.1002/cncr.70052","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Despite a short median PFS, certain histological subtypes, including ASPS, chordomas, SMARCA4-deficient tumors, gastro-intestinal stromal tumor, and <i>NF1</i> mutations, showed strong activity signals, indicating long-term responses in some patients.</p>\n </section>\n </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 18","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70052","citationCount":"0","resultStr":"{\"title\":\"Clinical and biological factors associated with response to immune checkpoint inhibitors in advanced sarcomas: IMPRESARC, a French retrospective multicenter cohort study\",\"authors\":\"Mina Fazel MD, Romain Varnier MD, Hélène Vanacker MD, PhD, Nicolas Penel MD, PhD, Sarah Watson MD, PhD, Benjamin Verret MD, Thibaud Valentin MD, Emmanuelle Bompas MD, Waisse Waissi MD, PhD, Alexandra Meurgey MD, Françoise Ducimetière PhD, Jean-Yves Blay MD, PhD, Armelle Dufresne MD, PhD, Mehdi Brahmi MD, PhD\",\"doi\":\"10.1002/cncr.70052\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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. 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Clinical and biological factors associated with response to immune checkpoint inhibitors in advanced sarcomas: IMPRESARC, a French retrospective multicenter cohort study
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.
期刊介绍：
The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society.
CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research
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