{"title":"S-1 +奥沙利铂与改良FOLFIRINOX在吉西他滨+ nab-紫杉醇失败后治疗晚期胰腺腺癌","authors":"Hui Tang, Zhengxia Li, Tingting You, Jinrong Ying, Mingming Yuan, Yuejuan Cheng, Yingyi Wang, Huanwen Wu, Chunmei Bai","doi":"10.1177/17588359251378698","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>There is no clear consensus on second-line chemotherapy for patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of first-line gemcitabine plus nab-paclitaxel (GnP).</p><p><strong>Objectives: </strong>This study aimed to compare the efficacy and safety of oxaliplatin plus S-1 (SOX) versus modified FOLFIRINOX (mFFX) as second-line chemotherapy in this patient population.</p><p><strong>Design: </strong>A retrospective cohort study was conducted.</p><p><strong>Methods: </strong>Patients with advanced PDAC who received second-line SOX or mFFX after GnP failure at Peking Union Medical College Hospital were reviewed. Efficacy (disease control rate (DCR), overall survival (OS), progression-free survival (PFS)), and safety were analyzed. Molecular features were explored in a subgroup using targeted next-generation sequencing (NGS).</p><p><strong>Results: </strong>In total, 113 patients were included (65 SOX, 48 mFFX). The mFFX group had a significantly higher DCR than the SOX group (68.8% vs 40.0%, <i>p</i> = 0.005). Median PFS (4.8 vs 2.4 months, <i>p</i> = 0.001) and OS (10.4 vs 6.1 months, <i>p</i> = 0.001) were significantly longer with mFFX, even after propensity score matching adjustment. However, grade ⩾3 adverse events, particularly severe neutropenia (42.9% vs 13.5%, <i>p</i> = 0.004) and diarrhea (17.1% vs 1.9%, <i>p</i> = 0.031), were more frequent with mFFX. Multivariate analysis confirmed mFFX as an independent predictor for improved PFS (hazard ratio (HR) = 0.52, <i>p</i> = 0.004) and OS (HR = 0.46, <i>p</i> = 0.002). Exploratory NGS analysis in 45 patients suggested ARID1A, INPP4A, NTRK2, and PTPRS alterations may predict poor survival, but did not influence the relative efficacy of either regimen.</p><p><strong>Conclusion: </strong>The mFFX regimen demonstrated superior efficacy over SOX as second-line chemotherapy after GnP failure in advanced PDAC, significantly prolonging PFS and OS. However, this benefit was accompanied by a higher incidence of severe toxicities. Molecular alterations may hold prognostic value but did not guide regimen selection in this study.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251378698"},"PeriodicalIF":4.2000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464396/pdf/","citationCount":"0","resultStr":"{\"title\":\"S-1 plus oxaliplatin versus modified FOLFIRINOX for advanced pancreatic adenocarcinoma after gemcitabine plus nab-paclitaxel failure.\",\"authors\":\"Hui Tang, Zhengxia Li, Tingting You, Jinrong Ying, Mingming Yuan, Yuejuan Cheng, Yingyi Wang, Huanwen Wu, Chunmei Bai\",\"doi\":\"10.1177/17588359251378698\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>There is no clear consensus on second-line chemotherapy for patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of first-line gemcitabine plus nab-paclitaxel (GnP).</p><p><strong>Objectives: </strong>This study aimed to compare the efficacy and safety of oxaliplatin plus S-1 (SOX) versus modified FOLFIRINOX (mFFX) as second-line chemotherapy in this patient population.</p><p><strong>Design: </strong>A retrospective cohort study was conducted.</p><p><strong>Methods: </strong>Patients with advanced PDAC who received second-line SOX or mFFX after GnP failure at Peking Union Medical College Hospital were reviewed. Efficacy (disease control rate (DCR), overall survival (OS), progression-free survival (PFS)), and safety were analyzed. Molecular features were explored in a subgroup using targeted next-generation sequencing (NGS).</p><p><strong>Results: </strong>In total, 113 patients were included (65 SOX, 48 mFFX). The mFFX group had a significantly higher DCR than the SOX group (68.8% vs 40.0%, <i>p</i> = 0.005). Median PFS (4.8 vs 2.4 months, <i>p</i> = 0.001) and OS (10.4 vs 6.1 months, <i>p</i> = 0.001) were significantly longer with mFFX, even after propensity score matching adjustment. However, grade ⩾3 adverse events, particularly severe neutropenia (42.9% vs 13.5%, <i>p</i> = 0.004) and diarrhea (17.1% vs 1.9%, <i>p</i> = 0.031), were more frequent with mFFX. Multivariate analysis confirmed mFFX as an independent predictor for improved PFS (hazard ratio (HR) = 0.52, <i>p</i> = 0.004) and OS (HR = 0.46, <i>p</i> = 0.002). Exploratory NGS analysis in 45 patients suggested ARID1A, INPP4A, NTRK2, and PTPRS alterations may predict poor survival, but did not influence the relative efficacy of either regimen.</p><p><strong>Conclusion: </strong>The mFFX regimen demonstrated superior efficacy over SOX as second-line chemotherapy after GnP failure in advanced PDAC, significantly prolonging PFS and OS. However, this benefit was accompanied by a higher incidence of severe toxicities. Molecular alterations may hold prognostic value but did not guide regimen selection in this study.</p>\",\"PeriodicalId\":23053,\"journal\":{\"name\":\"Therapeutic Advances in Medical Oncology\",\"volume\":\"17 \",\"pages\":\"17588359251378698\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464396/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17588359251378698\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359251378698","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：对于晚期胰腺导管腺癌（PDAC）患者在一线吉西他滨+ nab-紫杉醇（GnP）治疗失败后的二线化疗，目前还没有明确的共识。目的：本研究旨在比较奥沙利铂加S-1 （SOX）与改良FOLFIRINOX （mFFX）作为二线化疗在该患者群体中的疗效和安全性。设计：进行回顾性队列研究。方法：回顾性分析北京协和医院晚期PDAC患者GnP失败后接受二线SOX或mFFX治疗的病例。分析疗效(疾病控制率（DCR）、总生存期（OS）、无进展生存期（PFS）和安全性。利用靶向新一代测序（NGS）研究了一个亚群的分子特征。结果：共纳入113例患者（65例SOX， 48例mFFX）。mFFX组的DCR显著高于SOX组（68.8% vs 40.0%, p = 0.005）。mFFX的中位PFS （4.8 vs 2.4个月，p = 0.001）和OS （10.4 vs 6.1个月，p = 0.001）显着延长，即使在倾向评分匹配调整后也是如此。然而，小于3级的不良事件，特别是严重中性粒细胞减少症（42.9% vs 13.5%, p = 0.004）和腹泻（17.1% vs 1.9%, p = 0.031）在mFFX中更常见。多因素分析证实mFFX是改善PFS（风险比(HR) = 0.52, p = 0.004）和OS （HR = 0.46, p = 0.002）的独立预测因子。45例患者的探索性NGS分析表明，ARID1A、INPP4A、NTRK2和PTPRS的改变可能预示较差的生存，但不影响两种方案的相对疗效。结论：作为晚期PDAC患者GnP失败后的二线化疗方案，mFFX方案的疗效优于SOX方案，显著延长PFS和OS。然而，这一益处伴随着较高的严重毒性发生率。分子改变可能具有预后价值，但在本研究中没有指导方案选择。
S-1 plus oxaliplatin versus modified FOLFIRINOX for advanced pancreatic adenocarcinoma after gemcitabine plus nab-paclitaxel failure.
Background: There is no clear consensus on second-line chemotherapy for patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of first-line gemcitabine plus nab-paclitaxel (GnP).
Objectives: This study aimed to compare the efficacy and safety of oxaliplatin plus S-1 (SOX) versus modified FOLFIRINOX (mFFX) as second-line chemotherapy in this patient population.
Design: A retrospective cohort study was conducted.
Methods: Patients with advanced PDAC who received second-line SOX or mFFX after GnP failure at Peking Union Medical College Hospital were reviewed. Efficacy (disease control rate (DCR), overall survival (OS), progression-free survival (PFS)), and safety were analyzed. Molecular features were explored in a subgroup using targeted next-generation sequencing (NGS).
Results: In total, 113 patients were included (65 SOX, 48 mFFX). The mFFX group had a significantly higher DCR than the SOX group (68.8% vs 40.0%, p = 0.005). Median PFS (4.8 vs 2.4 months, p = 0.001) and OS (10.4 vs 6.1 months, p = 0.001) were significantly longer with mFFX, even after propensity score matching adjustment. However, grade ⩾3 adverse events, particularly severe neutropenia (42.9% vs 13.5%, p = 0.004) and diarrhea (17.1% vs 1.9%, p = 0.031), were more frequent with mFFX. Multivariate analysis confirmed mFFX as an independent predictor for improved PFS (hazard ratio (HR) = 0.52, p = 0.004) and OS (HR = 0.46, p = 0.002). Exploratory NGS analysis in 45 patients suggested ARID1A, INPP4A, NTRK2, and PTPRS alterations may predict poor survival, but did not influence the relative efficacy of either regimen.
Conclusion: The mFFX regimen demonstrated superior efficacy over SOX as second-line chemotherapy after GnP failure in advanced PDAC, significantly prolonging PFS and OS. However, this benefit was accompanied by a higher incidence of severe toxicities. Molecular alterations may hold prognostic value but did not guide regimen selection in this study.
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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