{"title":"TAS-102联合舒法替尼治疗三线及晚期转移性胰腺癌的疗效和安全性:一项前瞻性、单中心和生物标志物探索性II期研究","authors":"Yunxin Lu, Qingguang Lin, Yongxin Mo, Furong Liu, Mengwei Zhang, Runjie Huang, Yun Wang, Yinnan Wang, Zhiqiang Wang, Huiyan Luo, Guifang Guo, Jianwen Chen, Yu Liu, Mingming He, Fenghua Wang, Feng Wang, Dongsheng Zhang","doi":"10.1186/s12943-025-02437-0","DOIUrl":null,"url":null,"abstract":"Metastatic pancreatic cancer (mPC) has a dismal prognosis, with first line systemic therapy relying primarily on FOLFIRINOX (5FU/irinotecan/oxaliplatin) or AG (Gemcitabine/Nab-Paclitaxel). Therapeutic options for mPC refractory to these regimens remain poorly defined, and data on later-line options are scarce. This prospective, single-arm study evaluated the safety and preliminary efficacy of combining the anti-angiogenic agent surufatinib with the cytotoxic drug TAS-102 (Trifluridine/Tipiracil) in mPC patients who had progressed on ≥ 2 prior lines of therapy. mPC patients who were refractory to at least 2 previous regimens were enrolled and received TAS-102 (35 mg/m2, po, bid, D1-D5, D8-D12) plus surufatinib (250 mg, po, qd) in a 4-week cycle. The tumor response was assessed by the researcher every 8 weeks and treatment continued until disease progression, unacceptable toxicity, investigator discretion, or patient withdrawal of informed consent. Primary and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Between January 2023 and June 2024, 22 patients were enrolled into this study. Among 20 patients analyzed for efficacy, median PFS was 2.35 months (95% CI: 1.91–3.94) and median OS was 6.34 months (95% CI: 3.81–10.09). The ORR and DCR were 20% (4/20; all partial response) and 30% (6/20), respectively. All patients experienced treatment emergent adverse events (TEAEs), with anemia (59.1%), neutropenia (54.6%), leukocytopenia (50.0%), and lymphocytopenia (45.5%) as the most common any-grade events. Grade ≥ 3 TEAEs including neutropenia (31.8%), lymphocytopenia (13.6%), and anemia (9.1%), were observed in 50.0% (11/22) of patients. Subgroup analysis identified metastases involving > 2 organs or hepatic sites as potential predicative biomarkers for inferior efficacy. Proteomic screening revealed that overexpressed OCIAD2 correlated with poor prognosis, a finding validated in two publicly available external cohorts (CPTAC database and RuiJin cohort). Combination of TAS-102 and surufatinib demonstrates clinically meaningful efficacy and manageable toxicity as therapeutic option for later-line mPC. The biomarkers identified in this study may hold the potential to guide patient stratification and warrant further investigation to optimize precision application of this regimen. This study was prospectively registered at clinicaltrials.gov with the number NCT05481463 on August 1st 2022.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"92 1","pages":""},"PeriodicalIF":33.9000,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy and safety of TAS-102 plus Surufatinib in third and later line metastatic pancreatic cancer: a prospective, single center and biomarker exploratory, phase II study\",\"authors\":\"Yunxin Lu, Qingguang Lin, Yongxin Mo, Furong Liu, Mengwei Zhang, Runjie Huang, Yun Wang, Yinnan Wang, Zhiqiang Wang, Huiyan Luo, Guifang Guo, Jianwen Chen, Yu Liu, Mingming He, Fenghua Wang, Feng Wang, Dongsheng Zhang\",\"doi\":\"10.1186/s12943-025-02437-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Metastatic pancreatic cancer (mPC) has a dismal prognosis, with first line systemic therapy relying primarily on FOLFIRINOX (5FU/irinotecan/oxaliplatin) or AG (Gemcitabine/Nab-Paclitaxel). Therapeutic options for mPC refractory to these regimens remain poorly defined, and data on later-line options are scarce. This prospective, single-arm study evaluated the safety and preliminary efficacy of combining the anti-angiogenic agent surufatinib with the cytotoxic drug TAS-102 (Trifluridine/Tipiracil) in mPC patients who had progressed on ≥ 2 prior lines of therapy. mPC patients who were refractory to at least 2 previous regimens were enrolled and received TAS-102 (35 mg/m2, po, bid, D1-D5, D8-D12) plus surufatinib (250 mg, po, qd) in a 4-week cycle. The tumor response was assessed by the researcher every 8 weeks and treatment continued until disease progression, unacceptable toxicity, investigator discretion, or patient withdrawal of informed consent. Primary and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Between January 2023 and June 2024, 22 patients were enrolled into this study. Among 20 patients analyzed for efficacy, median PFS was 2.35 months (95% CI: 1.91–3.94) and median OS was 6.34 months (95% CI: 3.81–10.09). The ORR and DCR were 20% (4/20; all partial response) and 30% (6/20), respectively. All patients experienced treatment emergent adverse events (TEAEs), with anemia (59.1%), neutropenia (54.6%), leukocytopenia (50.0%), and lymphocytopenia (45.5%) as the most common any-grade events. Grade ≥ 3 TEAEs including neutropenia (31.8%), lymphocytopenia (13.6%), and anemia (9.1%), were observed in 50.0% (11/22) of patients. Subgroup analysis identified metastases involving > 2 organs or hepatic sites as potential predicative biomarkers for inferior efficacy. Proteomic screening revealed that overexpressed OCIAD2 correlated with poor prognosis, a finding validated in two publicly available external cohorts (CPTAC database and RuiJin cohort). Combination of TAS-102 and surufatinib demonstrates clinically meaningful efficacy and manageable toxicity as therapeutic option for later-line mPC. The biomarkers identified in this study may hold the potential to guide patient stratification and warrant further investigation to optimize precision application of this regimen. 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Efficacy and safety of TAS-102 plus Surufatinib in third and later line metastatic pancreatic cancer: a prospective, single center and biomarker exploratory, phase II study
Metastatic pancreatic cancer (mPC) has a dismal prognosis, with first line systemic therapy relying primarily on FOLFIRINOX (5FU/irinotecan/oxaliplatin) or AG (Gemcitabine/Nab-Paclitaxel). Therapeutic options for mPC refractory to these regimens remain poorly defined, and data on later-line options are scarce. This prospective, single-arm study evaluated the safety and preliminary efficacy of combining the anti-angiogenic agent surufatinib with the cytotoxic drug TAS-102 (Trifluridine/Tipiracil) in mPC patients who had progressed on ≥ 2 prior lines of therapy. mPC patients who were refractory to at least 2 previous regimens were enrolled and received TAS-102 (35 mg/m2, po, bid, D1-D5, D8-D12) plus surufatinib (250 mg, po, qd) in a 4-week cycle. The tumor response was assessed by the researcher every 8 weeks and treatment continued until disease progression, unacceptable toxicity, investigator discretion, or patient withdrawal of informed consent. Primary and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Between January 2023 and June 2024, 22 patients were enrolled into this study. Among 20 patients analyzed for efficacy, median PFS was 2.35 months (95% CI: 1.91–3.94) and median OS was 6.34 months (95% CI: 3.81–10.09). The ORR and DCR were 20% (4/20; all partial response) and 30% (6/20), respectively. All patients experienced treatment emergent adverse events (TEAEs), with anemia (59.1%), neutropenia (54.6%), leukocytopenia (50.0%), and lymphocytopenia (45.5%) as the most common any-grade events. Grade ≥ 3 TEAEs including neutropenia (31.8%), lymphocytopenia (13.6%), and anemia (9.1%), were observed in 50.0% (11/22) of patients. Subgroup analysis identified metastases involving > 2 organs or hepatic sites as potential predicative biomarkers for inferior efficacy. Proteomic screening revealed that overexpressed OCIAD2 correlated with poor prognosis, a finding validated in two publicly available external cohorts (CPTAC database and RuiJin cohort). Combination of TAS-102 and surufatinib demonstrates clinically meaningful efficacy and manageable toxicity as therapeutic option for later-line mPC. The biomarkers identified in this study may hold the potential to guide patient stratification and warrant further investigation to optimize precision application of this regimen. This study was prospectively registered at clinicaltrials.gov with the number NCT05481463 on August 1st 2022.
期刊介绍:
Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer.
The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies.
Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.