{"title":"Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration.","authors":"Yunxin Lu, Yin Jin, Furong Liu, Zixian Wang, Wen Zhou, Yang Zhang, Bing Bai, Yun Wang, Zhiqiang Wang, Man Nie, Huiyan Luo, Xiaoli Wei, Chuqiao Liang, Guifang Guo, Miaozhen Qiu, Jianwen Chen, Yu Liu, Shengping Li, Yuhong Li, Fenghua Wang, Feng Wang, Peidong Chi, Dongsheng Zhang","doi":"10.1007/s00262-024-03796-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking.</p><p><strong>Methods: </strong>ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing.</p><p><strong>Results: </strong>A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival.</p><p><strong>Conclusion: </strong>This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377375/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Immunology, Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00262-024-03796-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking.
Methods: ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing.
Results: A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival.
Conclusion: This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.
背景：抗PD-L1抗体durvalumab已被批准用于一线晚期胆管癌（ABC）。迄今为止，尚缺乏预测疗效的生物标志物：方法：回顾性入组接受吉西他滨为基础的化疗并使用或不使用durvalumab的ABC患者，并从病历中检索他们的基线临床病理指标。计算并分析总生存期（OS）和无进展生存期（PFS）。使用酶联免疫吸附试验等检测试剂盒检测了 48 例患者的外周生物标志物水平。通过靶向新一代测序描绘了可获得肿瘤组织的27名患者的基因组变化：2020年1月至2022年12月期间，共有186名符合纳入标准的ABC患者最终被纳入本研究。其中，93名患者接受了杜瓦鲁单抗联合化疗，其余患者接受了单独化疗。与单独化疗相比，Durvalumab联合化疗可显著改善既往未接受过治疗的ABC患者的PFS（6.77个月 vs. 4.99个月；危险比0.65 [95% CI 0.48-0.88]；P = 0.005），但OS（14.29个月 vs. 13.24个月；危险比0.91 [95% CI 0.62-1.32]；P = 0.608）却没有改善。接受化疗和不接受杜伐单抗治疗的患者的客观反应率（ORR）分别为19.1%和7.8%。治疗前的sPD-L1、CSF1R和OPG被确定为接受度伐卢单抗治疗患者的重要预后预测因子。ADGRB3和RNF43突变在对化疗加杜瓦鲁单抗有反应的患者中富集，并与较好的生存期相关：这项回顾性真实世界研究证实，在治疗无效的ABC患者中，度瓦鲁单抗联合化疗可带来临床获益。外周sPD-L1和CSF1R是这一治疗策略很有希望的预后生物标志物。ADGRB3或RNF43突变的存在可改善免疫治疗结果的分层，但仍需进一步研究以探索其潜在机制。
期刊介绍：
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions.
The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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