Pub Date : 2025-12-12DOI: 10.1016/j.esmogo.2025.100277
J. Dekervel , A. Vogel , E. O’Reilly
{"title":"ESMO podcast on upper GI cancers: highlights in hepatocellular carcinoma and pancreatic cancer from ESMO 2025","authors":"J. Dekervel , A. Vogel , E. O’Reilly","doi":"10.1016/j.esmogo.2025.100277","DOIUrl":"10.1016/j.esmogo.2025.100277","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100277"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145738835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.esmogo.2025.100267
K. Sato , I. Nakayama , M. Yura , A. Sato , M. Suzuki , T. Kadota , M. Nakamura , N. Sakamoto , T. Hashimoto , S. Sakashita , M. Wakabayashi , H. Shoji , T. Hayashi , H. Daiko , K. Kato , T. Yoshino , T. Yano , T. Fujita , T. Kinoshita , K. Shitara
Background
Durvalumab combined with fluorouracil, leucovorin, oxaliplatin, and docetaxel (D-FLOT) has demonstrated significant improvement in event-free survival (EFS) among patients with resectable gastric and gastroesophageal junction adenocarcinoma (GEJA) and is expected to become a new standard of care. Nevertheless, surgical resection remains requisite and is associated with substantial morbidity and deterioration in quality of life for GEJA. Given that D-FLOT achieves a pathological complete response in ∼20% of patients, intensification of total neoadjuvant therapy with short-course radiation (SRT) could further increase clinical CR (cCR) rates and facilitate non-operative management (NOM) in selected GEJA patients.
Trial design
EPOC2301 is a single-arm, phase II study evaluating the efficacy and safety of pembrolizumab with FLOT plus SRT as total neoadjuvant therapy for resectable GEJA. Patients receive two cycles of FLOT and one dose of pembrolizumab, followed by 25 Gy radiotherapy, then two more cycles of FLOT and one dose of pembrolizumab. Response is assessed by computed tomography, positron emission tomography-computed tomography, endoscopy with bite-on-bite biopsy, and whole-genome circulating tumor DNA analysis. Patients achieving cCR or near-cCR continue NOM with pembrolizumab and FLOT, whereas those without adequate response undergo surgery followed by adjuvant pembrolizumab and FLOT. The primary endpoint is 3-year EFS.
{"title":"An open label phase II study of total neoadjuvant therapy (TNT) consisting of FLOT with pembrolizumab and short radiation for patients with locally advanced gastroesophageal junction adenocarcinoma (EPOC2301)","authors":"K. Sato , I. Nakayama , M. Yura , A. Sato , M. Suzuki , T. Kadota , M. Nakamura , N. Sakamoto , T. Hashimoto , S. Sakashita , M. Wakabayashi , H. Shoji , T. Hayashi , H. Daiko , K. Kato , T. Yoshino , T. Yano , T. Fujita , T. Kinoshita , K. Shitara","doi":"10.1016/j.esmogo.2025.100267","DOIUrl":"10.1016/j.esmogo.2025.100267","url":null,"abstract":"<div><h3>Background</h3><div>Durvalumab combined with fluorouracil, leucovorin, oxaliplatin, and docetaxel (D-FLOT) has demonstrated significant improvement in event-free survival (EFS) among patients with resectable gastric and gastroesophageal junction adenocarcinoma (GEJA) and is expected to become a new standard of care. Nevertheless, surgical resection remains requisite and is associated with substantial morbidity and deterioration in quality of life for GEJA. Given that D-FLOT achieves a pathological complete response in ∼20% of patients, intensification of total neoadjuvant therapy with short-course radiation (SRT) could further increase clinical CR (cCR) rates and facilitate non-operative management (NOM) in selected GEJA patients.</div></div><div><h3>Trial design</h3><div>EPOC2301 is a single-arm, phase II study evaluating the efficacy and safety of pembrolizumab with FLOT plus SRT as total neoadjuvant therapy for resectable GEJA. Patients receive two cycles of FLOT and one dose of pembrolizumab, followed by 25 Gy radiotherapy, then two more cycles of FLOT and one dose of pembrolizumab. Response is assessed by computed tomography, positron emission tomography-computed tomography, endoscopy with bite-on-bite biopsy, and whole-genome circulating tumor DNA analysis. Patients achieving cCR or near-cCR continue NOM with pembrolizumab and FLOT, whereas those without adequate response undergo surgery followed by adjuvant pembrolizumab and FLOT. The primary endpoint is 3-year EFS.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100267"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.esmogo.2025.100260
A. Petrillo , F. Pietrantonio , I. Ben-Aharon
{"title":"Highlights in oesophagogastric cancers from ESMO GI cancers congress 2025","authors":"A. Petrillo , F. Pietrantonio , I. Ben-Aharon","doi":"10.1016/j.esmogo.2025.100260","DOIUrl":"10.1016/j.esmogo.2025.100260","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100260"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.esmogo.2025.100272
F. Lo Prinzi , S. Camera , S. Foti , M. Persano , C.M. Gullotta , F. Rossari , F. Vitiello , L. Passeri , F. Michele , A. Casadei-Gardini , M. Rimini
Background
Fibrolamellar carcinoma (FLC) is a rare subtype of hepatocellular carcinoma (HCC), accounting for ∼1%-9% of all HCC cases. The limited literature and lack of studies on FLC present significant challenges.
Patients and methods
We conducted a retrospective analysis using TriNetX data to evaluate patients’ characteristics and outcome in terms of overall survival (OS), among patients with FLC. Additionally, we conducted further analysis to evaluate differences in terms of patient characteristics and outcome between FLC and HCC; specifically, we compared patients with FLC and HCC who underwent any type of treatment, patients with FLC and HCC in the early stage who underwent surgery and patients with FLC and HCC with advanced disease treated in first-line therapy. Also, the same analyses were carried out after propensity score matching. The primary endpoints were features of patients and OS of FLC, and HCC versus FLC, particularly regarding systemic therapy and surgical interventions.
Results
In the FLC group, 87 patients were analyzed, with a median OS (mOS) of 56.1 months. Comparing HCC and FLC, 211 523 HCC patients and 87 FLC patients were included, showing no significant mOS difference [mOS 46.9 months versus 76.5 months, hazard ratio (HR) 1.21, P = 0.27], revealing significant differences in mean age (P < 0.0001) and racial distribution (P < 0.03). After propensity scoring, significant difference in α-fetoprotein (AFP) (P = 0.003) was discovered. In surgical cases, 116 276 HCC patients and 51 FLC patients had similar mOS (84.6 months versus 78.4 months, HR 0.94, P = 0.77), with significant differences in mean age (P < 0.001), racial distribution (P = 0.0002), and body mass index (BMI) (P = 0.04). The propensity score revealed a significant difference in aspartate aminotransferase value (P = 0.04). In first-line treatments, 6090 HCC patients and 22 FLC patients showed no statistical difference in mOS (8.1 months versus 26.0 months, HR 1.44, P = 0.13), but differences were found in gender distribution (P = 0.0003), mean age (P < 0.001), albumin levels (P = 0.01), and AFP values (P = 0.02). After propensity score matching, the analysis confirmed significant differences in AFP (P = 0.04) and total bilirubin value (P = 0.02).
Conclusion
The current analysis showed no statistically significant differences in OS between patients with HCC and those with FLC at any stage, regardless of whether they received surgical or medical treatment. Significant statistical features were highlighted between the groups.
{"title":"Clinical characteristics and outcome of patients with fibrolamellar hepatocellular carcinoma: an analysis of a large population using real-world data","authors":"F. Lo Prinzi , S. Camera , S. Foti , M. Persano , C.M. Gullotta , F. Rossari , F. Vitiello , L. Passeri , F. Michele , A. Casadei-Gardini , M. Rimini","doi":"10.1016/j.esmogo.2025.100272","DOIUrl":"10.1016/j.esmogo.2025.100272","url":null,"abstract":"<div><h3>Background</h3><div>Fibrolamellar carcinoma (FLC) is a rare subtype of hepatocellular carcinoma (HCC), accounting for ∼1%-9% of all HCC cases. The limited literature and lack of studies on FLC present significant challenges.</div></div><div><h3>Patients and methods</h3><div>We conducted a retrospective analysis using TriNetX data to evaluate patients’ characteristics and outcome in terms of overall survival (OS), among patients with FLC. Additionally, we conducted further analysis to evaluate differences in terms of patient characteristics and outcome between FLC and HCC; specifically, we compared patients with FLC and HCC who underwent any type of treatment, patients with FLC and HCC in the early stage who underwent surgery and patients with FLC and HCC with advanced disease treated in first-line therapy. Also, the same analyses were carried out after propensity score matching. The primary endpoints were features of patients and OS of FLC, and HCC versus FLC, particularly regarding systemic therapy and surgical interventions.</div></div><div><h3>Results</h3><div>In the FLC group, 87 patients were analyzed, with a median OS (mOS) of 56.1 months. Comparing HCC and FLC, 211 523 HCC patients and 87 FLC patients were included, showing no significant mOS difference [mOS 46.9 months versus 76.5 months, hazard ratio (HR) 1.21, <em>P</em> = 0.27], revealing significant differences in mean age (<em>P</em> < 0.0001) and racial distribution (<em>P</em> < 0.03). After propensity scoring, significant difference in α-fetoprotein (AFP) (<em>P</em> = 0.003) was discovered. In surgical cases, 116 276 HCC patients and 51 FLC patients had similar mOS (84.6 months versus 78.4 months, HR 0.94, <em>P</em> = 0.77), with significant differences in mean age (<em>P</em> < 0.001), racial distribution (<em>P</em> = 0.0002), and body mass index (BMI) (<em>P</em> = 0.04). The propensity score revealed a significant difference in aspartate aminotransferase value (<em>P</em> = 0.04). In first-line treatments, 6090 HCC patients and 22 FLC patients showed no statistical difference in mOS (8.1 months versus 26.0 months, HR 1.44, <em>P</em> = 0.13), but differences were found in gender distribution (<em>P</em> = 0.0003), mean age (<em>P</em> < 0.001), albumin levels (<em>P</em> = 0.01), and AFP values (<em>P</em> = 0.02). After propensity score matching, the analysis confirmed significant differences in AFP (<em>P</em> = 0.04) and total bilirubin value (<em>P</em> = 0.02).</div></div><div><h3>Conclusion</h3><div>The current analysis showed no statistically significant differences in OS between patients with HCC and those with FLC at any stage, regardless of whether they received surgical or medical treatment. Significant statistical features were highlighted between the groups.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100272"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.esmogo.2025.100270
A. El Kaddissi , A. Vienot , J.-D. Fumet , A. Meurisse , T. Nguyen , E. Klajer , A. Bouard , L. Spehner , F. Fein , M. Stouvenot , E. Dochy , M. Rebucci-Peixoto , H. Almotlak , J. Henriquez , Z. Selmani , D. Vernerey , E. Hervouet , A. Folletet , S. Kim , F. Ghiringhelli , C. Borg
Background
Treatment of chemotherapy-resistant metastatic colorectal cancers (mCRCs) is still an unmet medical need. Combining regorafenib, an antiangiogenic multikinase inhibitor with metronomic chemotherapy and aspirin may enhance efficacy to circumvent the tumor microenvironment and offer better clinical outcomes. REPROGRAM-01 was a signal-seeking phase II study assessing the efficacy and safety of multimodal metronomic chemotherapy combined with regorafenib (NCT04534218).
Patients and methods
mCRC patients involved were previously exposed to conventional chemotherapies, bevacizumab, anti-epidermal growth factor receptor (anti-EGFR) if RAS wild type, and pembrolizumab if deficient mismatch repair disease. Regorafenib (starting dose 80 mg/day orally with weekly escalation, per 40 mg increment, to 160 mg/day) was combined with multimodal metronomic chemotherapy including capecitabine (625 mg/m2 twice daily continuously) and cyclophosphamide (50 mg daily) for 6 months plus aspirin (75 mg once daily). The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival (PFS), safety, and evaluation of exploratory biomarkers.
Results
Forty-eight patients were included. No unexpected serious adverse event was reported and 10 patients discontinued regorafenib for toxicity. The most common grade 3 and 4 toxicities involved palmoplantar erythrodysesthesia (14.6%), diarrhea (6.3%), hypertension (4.2%), and lymphopenia (4.2%). The best ORR was 4.2% [95% confidence interval (CI) 0.8% to 12.5%]. The trial was negative on the primary endpoint aiming to achieve an ORR of 15%, compared with 4% for null hypothesis. Median PFS and OS were 4.7 months (95% CI 3.7-5.9 months) and 9.5 months (95% CI 7.2-14.9 months), respectively. The PFS rates at 6 months and 12 months were 32.5% and 6.5%, respectively. A decrease of NPY methylated circulating tumor DNA >50% occurred in 16 out of the 26 assessable patients, leading to a median PFS of 5.5 months (95% CI 3.7-9.5 months) versus 3.6 (95% CI 1.8-9.6 months). A median PFS of 7.2 months (95% CI 3.7-11.6 months) was achieved in patients with decreasing angiopoietin-2 (ANG2) levels compared with 3.9 months (95% CI 1.3-19.4 months) in ANG2 nonresponding patients.
Conclusions
According to the REPROGRAM-01 study, combining multimodal metronomic chemotherapy with regorafenib would double the number of patients who could benefit from regorafenib treatment without increasing toxicities.
化疗耐药转移性结直肠癌(mccrcs)的治疗仍然是一个未满足的医学需求。regorafenib是一种抗血管生成的多激酶抑制剂,与节律化疗和阿司匹林联合使用可以提高疗效,绕过肿瘤微环境,提供更好的临床结果。REPROGRAM-01是一项信号寻求的II期研究,评估多模式节律化疗联合瑞戈非尼(NCT04534218)的有效性和安全性。患者和方法参与的smcrc患者先前暴露于常规化疗,贝伐单抗,抗表皮生长因子受体(抗egfr)(如果是RAS野生型)和派姆单抗(如果是缺陷错配修复疾病)。Regorafenib(起始剂量为口服80 mg/天,每周递增,每增加40 mg,至160 mg/天)联合多模式节律化疗,包括卡培他滨(625 mg/m2,每日2次,连续)和环磷酰胺(每日50 mg),持续6个月,外加阿司匹林(75 mg,每日1次)。主要终点为客观缓解率(ORR)。次要终点是总生存期(OS)、无进展生存期(PFS)、安全性和探索性生物标志物的评估。结果纳入48例患者。没有意外的严重不良事件报告,10例患者因毒性停用瑞非尼。最常见的3级和4级毒性包括掌跖红肿(14.6%)、腹泻(6.3%)、高血压(4.2%)和淋巴细胞减少(4.2%)。最佳ORR为4.2%[95%可信区间(CI) 0.8% ~ 12.5%]。该试验的主要终点为阴性,目的是达到15%的ORR,而零假设的ORR为4%。中位PFS和OS分别为4.7个月(95% CI 3.7-5.9个月)和9.5个月(95% CI 7.2-14.9个月)。6个月和12个月的PFS率分别为32.5%和6.5%。在26名可评估的患者中,16名患者NPY甲基化循环肿瘤DNA减少了50%,导致中位PFS为5.5个月(95% CI 3.7-9.5个月),而3.6个月(95% CI 1.8-9.6个月)。血管生成素-2 (ANG2)水平下降的患者的中位PFS为7.2个月(95% CI 3.7-11.6个月),而ANG2无反应的患者为3.9个月(95% CI 1.3-19.4个月)。REPROGRAM-01研究表明,多模式节律化疗联合瑞非尼可使受益于瑞非尼治疗的患者数量增加一倍,且不增加毒性。
{"title":"Regorafenib and metronomic capecitabine, cyclophosphamide, and aspirin in refractory metastatic colorectal cancer: results from the REPROGRAM-01 single-arm phase II trial","authors":"A. El Kaddissi , A. Vienot , J.-D. Fumet , A. Meurisse , T. Nguyen , E. Klajer , A. Bouard , L. Spehner , F. Fein , M. Stouvenot , E. Dochy , M. Rebucci-Peixoto , H. Almotlak , J. Henriquez , Z. Selmani , D. Vernerey , E. Hervouet , A. Folletet , S. Kim , F. Ghiringhelli , C. Borg","doi":"10.1016/j.esmogo.2025.100270","DOIUrl":"10.1016/j.esmogo.2025.100270","url":null,"abstract":"<div><h3>Background</h3><div>Treatment of chemotherapy-resistant metastatic colorectal cancers (mCRCs) is still an unmet medical need. Combining regorafenib, an antiangiogenic multikinase inhibitor with metronomic chemotherapy and aspirin may enhance efficacy to circumvent the tumor microenvironment and offer better clinical outcomes. REPROGRAM-01 was a signal-seeking phase II study assessing the efficacy and safety of multimodal metronomic chemotherapy combined with regorafenib (NCT04534218).</div></div><div><h3>Patients and methods</h3><div>mCRC patients involved were previously exposed to conventional chemotherapies, bevacizumab, anti-epidermal growth factor receptor (anti-EGFR) if <em>RAS</em> wild type, and pembrolizumab if deficient mismatch repair disease. Regorafenib (starting dose 80 mg/day orally with weekly escalation, per 40 mg increment, to 160 mg/day) was combined with multimodal metronomic chemotherapy including capecitabine (625 mg/m<sup>2</sup> twice daily continuously) and cyclophosphamide (50 mg daily) for 6 months plus aspirin (75 mg once daily). The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival (PFS), safety, and evaluation of exploratory biomarkers.</div></div><div><h3>Results</h3><div>Forty-eight patients were included. No unexpected serious adverse event was reported and 10 patients discontinued regorafenib for toxicity. The most common grade 3 and 4 toxicities involved palmoplantar erythrodysesthesia (14.6%), diarrhea (6.3%), hypertension (4.2%), and lymphopenia (4.2%). The best ORR was 4.2% [95% confidence interval (CI) 0.8% to 12.5%]. The trial was negative on the primary endpoint aiming to achieve an ORR of 15%, compared with 4% for null hypothesis. Median PFS and OS were 4.7 months (95% CI 3.7-5.9 months) and 9.5 months (95% CI 7.2-14.9 months), respectively. The PFS rates at 6 months and 12 months were 32.5% and 6.5%, respectively. A decrease of NPY methylated circulating tumor DNA >50% occurred in 16 out of the 26 assessable patients, leading to a median PFS of 5.5 months (95% CI 3.7-9.5 months) versus 3.6 (95% CI 1.8-9.6 months). A median PFS of 7.2 months (95% CI 3.7-11.6 months) was achieved in patients with decreasing angiopoietin-2 (ANG2) levels compared with 3.9 months (95% CI 1.3-19.4 months) in ANG2 nonresponding patients.</div></div><div><h3>Conclusions</h3><div>According to the REPROGRAM-01 study, combining multimodal metronomic chemotherapy with regorafenib would double the number of patients who could benefit from regorafenib treatment without increasing toxicities.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100270"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.esmogo.2025.100269
T. Yamada , T. Hata , A. Ishiguro , Y. Munemoto , K. Kataoka , A. Hirose , A. Matsuda , H. Sonoda , H. Tanji , K. Ogihara , T. Ishikawa , N. Ishizuka , K. Yamazaki , T. Kato , K. Yamaguchi , T. Mizushima
Background
Oxaliplatin-based adjuvant chemotherapy improves recurrence-free survival in stage II/III colorectal cancer (CRC) patients. However, oxaliplatin treatment is frequently limited by chemotherapy-induced peripheral neuropathy (CIPN). Oxidative stress is implicated in CIPN pathogenesis. Lecithinized superoxide dismutase (PC-SOD) is a long-circulating antioxidant enzyme that has demonstrated favorable pharmacokinetics and safety in prior studies. This study aimed to evaluate the efficacy of PC-SOD in preventing oxaliplatin-induced CIPN.
Materials and methods
In this double-blind, placebo-controlled, randomized trial, patients with stage II/III CRC scheduled to receive 12 cycles of mFOLFOX6 were randomly assigned to receive intravenous PC-SOD (80 mg) or placebo before each oxaliplatin dose. The primary endpoint was the number of cycles until National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade ≥2 CIPN occurred. Secondary endpoints included time to Neurotoxicity Criteria of DEBIOPHARM (DEB-NTC) grade ≥2 CIPN. Post hoc exploratory analyses evaluated time to NCI-CTCAE grade ≥1 CIPN and infusion-related reaction (IRR).
Results
Ninety patients were enrolled (PC-SOD: n = 43; placebo: n = 47). The primary endpoint was not met [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.44-1.78, P = 0.72]. However, the PC-SOD group experienced delayed onset of DEB-NTC grade ≥2 CIPN (HR 0.73, 95% CI 0.48-1.12, P = 0.08) and NCI-CTCAE grade ≥1 CIPN (HR 0.62, 95% CI 0.40-0.96, P = 0.01, post hoc). The incidence of IRRs (post hoc) was notably lower in the PC-SOD group (7.0%) compared with placebo (23.4%).
Conclusions
This trial did not meet its primary endpoint, maybe due to underpowered sample size. PC-SOD showed a potential to delay the onset of oxaliplatin-induced CIPN and reduced IRR. A confirmatory study on a large scale and with adequate statistical power is needed.
以沙利铂为基础的辅助化疗可提高II/III期结直肠癌(CRC)患者的无复发生存率。然而,奥沙利铂的治疗经常受到化疗引起的周围神经病变(CIPN)的限制。氧化应激参与CIPN的发病机制。卵磷脂化超氧化物歧化酶(PC-SOD)是一种长周期循环的抗氧化酶,在先前的研究中已经证明了良好的药代动力学和安全性。本研究旨在评价PC-SOD对奥沙利铂诱导的CIPN的预防作用。材料和方法在这项双盲、安慰剂对照、随机试验中,计划接受12个周期mFOLFOX6的II/III期CRC患者被随机分配到每次奥沙利铂剂量前接受静脉注射PC-SOD (80 mg)或安慰剂。主要终点是美国国家癌症研究所不良事件通用术语标准(NCI-CTCAE)≥2级CIPN发生前的周期数。次要终点包括DEBIOPHARM (DEB-NTC)神经毒性标准≥2 CIPN的时间。事后探索性分析评估了NCI-CTCAE≥1级CIPN和输液相关反应(IRR)的时间。结果共纳入90例患者(PC-SOD: n = 43;安慰剂:n = 47)。主要终点未达到[风险比(HR) 0.88, 95%可信区间(CI) 0.44-1.78, P = 0.72]。然而,PC-SOD组出现debc - ntc级≥2 CIPN (HR 0.73, 95% CI 0.48-1.12, P = 0.08)和NCI-CTCAE级≥1 CIPN (HR 0.62, 95% CI 0.40-0.96, P = 0.01,事后分析)的延迟发作。与安慰剂组(23.4%)相比,PC-SOD组的IRRs(事后)发生率显著降低(7.0%)。该试验未达到其主要终点,可能是由于样本量不足。PC-SOD显示出延迟奥沙利铂诱导的CIPN发作和降低IRR的潜力。需要进行大规模的、具有足够统计能力的确证性研究。
{"title":"Lecithinized superoxide dismutase prevents oxaliplatin-induced peripheral neuropathy: a double-blind, placebo-controlled, randomized phase II study","authors":"T. Yamada , T. Hata , A. Ishiguro , Y. Munemoto , K. Kataoka , A. Hirose , A. Matsuda , H. Sonoda , H. Tanji , K. Ogihara , T. Ishikawa , N. Ishizuka , K. Yamazaki , T. Kato , K. Yamaguchi , T. Mizushima","doi":"10.1016/j.esmogo.2025.100269","DOIUrl":"10.1016/j.esmogo.2025.100269","url":null,"abstract":"<div><h3>Background</h3><div>Oxaliplatin-based adjuvant chemotherapy improves recurrence-free survival in stage II/III colorectal cancer (CRC) patients. However, oxaliplatin treatment is frequently limited by chemotherapy-induced peripheral neuropathy (CIPN). Oxidative stress is implicated in CIPN pathogenesis. Lecithinized superoxide dismutase (PC-SOD) is a long-circulating antioxidant enzyme that has demonstrated favorable pharmacokinetics and safety in prior studies. This study aimed to evaluate the efficacy of PC-SOD in preventing oxaliplatin-induced CIPN.</div></div><div><h3>Materials and methods</h3><div>In this double-blind, placebo-controlled, randomized trial, patients with stage II/III CRC scheduled to receive 12 cycles of mFOLFOX6 were randomly assigned to receive intravenous PC-SOD (80 mg) or placebo before each oxaliplatin dose. The primary endpoint was the number of cycles until National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade ≥2 CIPN occurred. Secondary endpoints included time to Neurotoxicity Criteria of DEBIOPHARM (DEB-NTC) grade ≥2 CIPN. <em>Post hoc</em> exploratory analyses evaluated time to NCI-CTCAE grade ≥1 CIPN and infusion-related reaction (IRR).</div></div><div><h3>Results</h3><div>Ninety patients were enrolled (PC-SOD: <em>n</em> = 43; placebo: <em>n</em> = 47). The primary endpoint was not met [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.44-1.78, <em>P</em> = 0.72]. However, the PC-SOD group experienced delayed onset of DEB-NTC grade ≥2 CIPN (HR 0.73, 95% CI 0.48-1.12, <em>P</em> = 0.08) and NCI-CTCAE grade ≥1 CIPN (HR 0.62, 95% CI 0.40-0.96, <em>P</em> = 0.01, <em>post hoc</em>). The incidence of IRRs (<em>post hoc</em>) was notably lower in the PC-SOD group (7.0%) compared with placebo (23.4%).</div></div><div><h3>Conclusions</h3><div>This trial did not meet its primary endpoint, maybe due to underpowered sample size. PC-SOD showed a potential to delay the onset of oxaliplatin-induced CIPN and reduced IRR. A confirmatory study on a large scale and with adequate statistical power is needed.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100269"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.esmogo.2025.100266
M. Yue , Y. Mao , F. Wang , Q. Yang , X. Yu , H. Tang , Y. Lan , L. Tan , W. Wang , S. Li , F. Wang
Background
Solid pseudopapillary neoplasm (SPN) of the pancreas is rare and indolent. However, some patients with malignant potential develop metastasis. We aimed to analyze current treatment status and explore optimized clinical management of metastatic SPNs.
Patients and methods
Clinical data of metastatic SPN patients were collected from literature and two hospitals. Gene set enrichment analysis of RNA expression profiles of tumor tissues versus normal pancreatic tissues from the GEO database was carried out to explore functionally enriched pathways. Fresh tumor tissues from 10 SPN patients were cultured and in vitro hormonal agent sensitivity testing was conducted. Six patients received endocrine therapy with tamoxifen and megestrol acetate.
Results
A total of 115 metastatic SPN patients were included. Eighty-four patients underwent local treatment, including surgery, interventional therapy, and radiotherapy. Cytoreductive therapy significantly improved overall survival (P < 0.05, hazard ratio 0.11, 95% confidence interval 0.02-0.68). Thirty-six patients received chemotherapy and only one achieved partial response. Concurrent enrichment of the Wnt signaling pathway and progesterone receptor signaling pathway in SPNs was revealed. Drug sensitivity testing showed inhibition rates (IRs) of 50% for megestrol acetate, 40% for tamoxifen, and 30% for testosterone propionate, and 20% for gemcitabine at 10 × peak plasma concentration (Cmax). There was a trend toward higher IR for megestrol acetate and tamoxifen in the 100% progesterone receptor expression subgroup. Six patients received endocrine therapy with tamoxifen plus megestrol acetate. Tumor regression was observed in two patients.
Conclusions
This largest-to-date retrospective study demonstrated the chemoresistant nature of SPN, survival benefits from cytoreductive therapy, and preliminary clinical response of endocrine therapy. The combination of tamoxifen and megestrol acetate is worthy of further exploration.
{"title":"Metastatic solid pseudopapillary neoplasms of the pancreas: current treatment status and exploration of endocrine therapy","authors":"M. Yue , Y. Mao , F. Wang , Q. Yang , X. Yu , H. Tang , Y. Lan , L. Tan , W. Wang , S. Li , F. Wang","doi":"10.1016/j.esmogo.2025.100266","DOIUrl":"10.1016/j.esmogo.2025.100266","url":null,"abstract":"<div><h3>Background</h3><div>Solid pseudopapillary neoplasm (SPN) of the pancreas is rare and indolent. However, some patients with malignant potential develop metastasis. We aimed to analyze current treatment status and explore optimized clinical management of metastatic SPNs.</div></div><div><h3>Patients and methods</h3><div>Clinical data of metastatic SPN patients were collected from literature and two hospitals. Gene set enrichment analysis of RNA expression profiles of tumor tissues versus normal pancreatic tissues from the GEO database was carried out to explore functionally enriched pathways. Fresh tumor tissues from 10 SPN patients were cultured and <em>in vitro</em> hormonal agent sensitivity testing was conducted. Six patients received endocrine therapy with tamoxifen and megestrol acetate.</div></div><div><h3>Results</h3><div>A total of 115 metastatic SPN patients were included. Eighty-four patients underwent local treatment, including surgery, interventional therapy, and radiotherapy. Cytoreductive therapy significantly improved overall survival (<em>P</em> < 0.05, hazard ratio 0.11, 95% confidence interval 0.02-0.68). Thirty-six patients received chemotherapy and only one achieved partial response. Concurrent enrichment of the Wnt signaling pathway and progesterone receptor signaling pathway in SPNs was revealed. Drug sensitivity testing showed inhibition rates (IRs) of 50% for megestrol acetate, 40% for tamoxifen, and 30% for testosterone propionate, and 20% for gemcitabine at 10 × peak plasma concentration (Cmax). There was a trend toward higher IR for megestrol acetate and tamoxifen in the 100% progesterone receptor expression subgroup. Six patients received endocrine therapy with tamoxifen plus megestrol acetate. Tumor regression was observed in two patients.</div></div><div><h3>Conclusions</h3><div>This largest-to-date retrospective study demonstrated the chemoresistant nature of SPN, survival benefits from cytoreductive therapy, and preliminary clinical response of endocrine therapy. The combination of tamoxifen and megestrol acetate is worthy of further exploration.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100266"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.1016/j.esmogo.2025.100268
C. Lin , T. Luo , M. Wu , F. Li , L. Nunes , A. Mezheyeuski , K. Hammarström , A. Isaksson , I. Ljuslinder , M. Uhlén , R. Palmqvist , S. Zhu , B. Glimelius , K. Wu , T. Sjöblom
Microsatellite-instable (MSI) tumours constitute one-fifth of colorectal cancers (CRCs). However, the MSI CRCs display substantial tumour microenvironment (TME) heterogeneity and variable responses to immunotherapy, necessitating a refined classification to guide personalized therapy. In this study, we analysed whole-genome and transcriptome sequences from 223 MSI CRC patients from a large prospective longitudinal cancer study in Sweden (Nunes L, Li F, Wu M, et al. Prognostic genome and transcriptome signatures in colorectal cancers. Nature. 2024;633(8028):137-146) and identified three molecular subclasses with distinct TME and genetic features: class 1a (immune-excluded), characterized by prominent stromal activation, transforming growth factor-β signalling, and low tumour neoantigen burdens (TNB); class 1b (immune-infiltrated), marked by intact neoantigen presentation and strong antitumour immunity; and class 2 (immune-cold), exhibiting epithelial features, high tumour mutation burden (TMB) and TNB, chromosomal instability, active metabolism, and a lack of immune activation. We further uncovered a correlation between mutL homolog 1 (MLH1) hypermethylation and the immune-cold phenotype in class 2, where anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) combination immunotherapy demonstrated significantly improved efficacy compared with anti-PD-1 monotherapy. Finally, the molecular features of these subclasses were validated in external MSI CRC cohorts and in MSI tumours from other cancers. Our findings offer a comprehensive understanding of the molecular landscape of MSI CRC, unveiling potential molecular mechanisms underlying different tumour-immune phenotypes and laying the foundation for future development of tailored treatment strategies.
{"title":"Molecular classification of microsatellite-instable colorectal cancers reveals distinct predictors of immunotherapy response","authors":"C. Lin , T. Luo , M. Wu , F. Li , L. Nunes , A. Mezheyeuski , K. Hammarström , A. Isaksson , I. Ljuslinder , M. Uhlén , R. Palmqvist , S. Zhu , B. Glimelius , K. Wu , T. Sjöblom","doi":"10.1016/j.esmogo.2025.100268","DOIUrl":"10.1016/j.esmogo.2025.100268","url":null,"abstract":"<div><div>Microsatellite-instable (MSI) tumours constitute one-fifth of colorectal cancers (CRCs). However, the MSI CRCs display substantial tumour microenvironment (TME) heterogeneity and variable responses to immunotherapy, necessitating a refined classification to guide personalized therapy. In this study, we analysed whole-genome and transcriptome sequences from 223 MSI CRC patients from a large prospective longitudinal cancer study in Sweden (Nunes L, Li F, Wu M, et al. Prognostic genome and transcriptome signatures in colorectal cancers. <em>Nature.</em> 2024;633(8028):137-146) and identified three molecular subclasses with distinct TME and genetic features: class 1a (immune-excluded), characterized by prominent stromal activation, transforming growth factor-β signalling, and low tumour neoantigen burdens (TNB); class 1b (immune-infiltrated), marked by intact neoantigen presentation and strong antitumour immunity; and class 2 (immune-cold), exhibiting epithelial features, high tumour mutation burden (TMB) and TNB, chromosomal instability, active metabolism, and a lack of immune activation. We further uncovered a correlation between mutL homolog 1 (<em>MLH1</em><em>)</em> hypermethylation and the immune-cold phenotype in class 2, where anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) combination immunotherapy demonstrated significantly improved efficacy compared with anti-PD-1 monotherapy. Finally, the molecular features of these subclasses were validated in external MSI CRC cohorts and in MSI tumours from other cancers. Our findings offer a comprehensive understanding of the molecular landscape of MSI CRC, unveiling potential molecular mechanisms underlying different tumour-immune phenotypes and laying the foundation for future development of tailored treatment strategies.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100268"},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1016/j.esmogo.2025.100262
A. Markussen , T.D. Christensen , L. Kaerlev , K. Madsen , S. Theile , N.A. Schultz , P.N. Larsen , G.L. Willemoe , D.L. Nielsen , J.S. Johansen , I.M. Chen , F.O. Larsen
Background
Despite recent treatment advancements, comprehensive real-world data on biliary tract cancer (BTC) treatment patterns and outcomes are essential. In this retrospective study, we assessed real-world treatment patterns and survival outcomes in a Danish cohort of patients with BTC.
Methods
Patients were identified using International Classification of Diseases, 10th Revision (ICD-10) codes in the Danish National Patient Register (period: 1 January 2010 to 31 December 2020). Prespecified data from the patients’ medical files were recorded.
Results
We identified 1340 patients and confirmed the diagnosis in 1028. This high misclassification rate was partly due to a broad inclusion of ICD-10 codes, including non-BTC-specific codes, and partly due to a true misclassification of other cancers. Based on the initial treatment strategy, surgery was possible for 277 patients (27.0%) with five perioperative deaths (1.8%), a recurrence rate of 68.8%, and a median overall survival of 29.9 months (95% confidence interval 26.2-36.6 months). Palliative chemotherapy was administered to 504 (49.0%) patients; 247 (24.0%) received no treatment. Combining patients with upfront unresectable disease and those with recurrent disease, 628 initiated first-line palliative chemotherapy; most received a combination treatment containing either oxaliplatin (n = 294, 46.8%) or cisplatin (n = 232, 36.9%). The median overall survival for treatment with cisplatin/gemcitabine was 11.2 months (95% confidence interval 9.5-13.1 months).
Conclusion
We comprehensively described the real-world treatment patterns in a Danish cohort of patients with BTC; specific ICD-10 codes could reliably identify this cohort of patients. Our findings highlight the need for improved treatment strategies in adjuvant and palliative settings.
{"title":"Real-world treatment patterns and outcomes in biliary tract cancer: a Danish retrospective cohort study","authors":"A. Markussen , T.D. Christensen , L. Kaerlev , K. Madsen , S. Theile , N.A. Schultz , P.N. Larsen , G.L. Willemoe , D.L. Nielsen , J.S. Johansen , I.M. Chen , F.O. Larsen","doi":"10.1016/j.esmogo.2025.100262","DOIUrl":"10.1016/j.esmogo.2025.100262","url":null,"abstract":"<div><h3>Background</h3><div>Despite recent treatment advancements, comprehensive real-world data on biliary tract cancer (BTC) treatment patterns and outcomes are essential. In this retrospective study, we assessed real-world treatment patterns and survival outcomes in a Danish cohort of patients with BTC.</div></div><div><h3>Methods</h3><div>Patients were identified using International Classification of Diseases, 10th Revision (ICD-10) codes in the Danish National Patient Register (period: 1 January 2010 to 31 December 2020). Prespecified data from the patients’ medical files were recorded.</div></div><div><h3>Results</h3><div>We identified 1340 patients and confirmed the diagnosis in 1028. This high misclassification rate was partly due to a broad inclusion of ICD-10 codes, including non-BTC-specific codes, and partly due to a true misclassification of other cancers. Based on the initial treatment strategy, surgery was possible for 277 patients (27.0%) with five perioperative deaths (1.8%), a recurrence rate of 68.8%, and a median overall survival of 29.9 months (95% confidence interval 26.2-36.6 months). Palliative chemotherapy was administered to 504 (49.0%) patients; 247 (24.0%) received no treatment. Combining patients with upfront unresectable disease and those with recurrent disease, 628 initiated first-line palliative chemotherapy; most received a combination treatment containing either oxaliplatin (<em>n</em> = 294, 46.8%) or cisplatin (<em>n</em> = 232, 36.9%). The median overall survival for treatment with cisplatin/gemcitabine was 11.2 months (95% confidence interval 9.5-13.1 months).</div></div><div><h3>Conclusion</h3><div>We comprehensively described the real-world treatment patterns in a Danish cohort of patients with BTC; specific ICD-10 codes could reliably identify this cohort of patients. Our findings highlight the need for improved treatment strategies in adjuvant and palliative settings.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100262"},"PeriodicalIF":0.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1016/j.esmogo.2025.100265
T. Satake, M. Sasaki, H. Imaoka, S. Taro, K. Inoue, T. Taira, G. Igarashi, M. Amisaki, H. Takahashi, S. Mitsunaga, M. Ikeda
Background and purpose
Following the TOPAZ-1 trial, chemoimmunotherapy with durvalumab plus gemcitabine and cisplatin (GCD) became the standard first-line treatment of advanced biliary tract cancer (BTC). This study aimed to compare the therapeutic efficacy of GCD and gemcitabine, cisplatin, and S-1 (GCS).
Methods
This single-center, retrospective study consecutively included patients with advanced BTC receiving primary treatment with GCD or GCS between November 2018 and August 2024.
Results
A total 265 patients with advanced BTC were included: 97 were treated with GCD and 168 were treated with GCS. Median overall survival (OS) was 17.1 months [95% confidence interval (CI) 12.7-20.6 months] in the GCD group versus 18.3 months (95% CI 15.4-20.4 months) in the GCS group, with no statistically significant difference (P = 0.509). Median progression-free survival (PFS) was 8.0 months (95% CI 5.9-9.6 months) in the GCD group versus 8.9 months (95% CI 7.1-11.4 months) in the GCS group (P = 0.077). No differences were noted in objective response rates, whereas median duration of response (DoR) was significantly longer in the GCS group (12.7 months) than that in the GCD group (7.5 months) (P = 0.022). Patients with ARID1A or PIK3CA alterations, or with SMAD4 wild-type, had better OS with GCS than with GCD.
Conclusion
GCD and GCS provide comparable survival outcomes and safety in clinical practice, with a significantly longer DoR in the GCS group. Alongside GCD, GCS represents one of the standard treatment options for advanced BTC.
背景与目的在TOPAZ-1试验之后,杜伐单抗联合吉西他滨和顺铂(GCD)的化学免疫治疗成为晚期胆道癌(BTC)的标准一线治疗。本研究旨在比较GCD与吉西他滨、顺铂和S-1 (GCS)的治疗效果。方法本研究为单中心回顾性研究,纳入2018年11月至2024年8月期间接受GCD或GCS初步治疗的晚期BTC患者。结果共纳入265例晚期BTC患者,其中GCD组97例,GCS组168例。GCD组的中位总生存期(OS)为17.1个月[95%可信区间(CI) 12.7-20.6个月],而GCS组的中位总生存期(OS)为18.3个月(95% CI 15.4-20.4个月),差异无统计学意义(P = 0.509)。GCD组的中位无进展生存期(PFS)为8.0个月(95% CI 5.9-9.6个月),而GCS组的中位无进展生存期(PFS)为8.9个月(95% CI 7.1-11.4个月)(P = 0.077)。客观缓解率无差异,而GCS组的中位缓解持续时间(DoR)(12.7个月)明显长于GCD组(7.5个月)(P = 0.022)。ARID1A或PIK3CA改变或SMAD4野生型患者,GCS患者的OS优于GCD患者。在临床实践中,cd和GCS提供了相当的生存结果和安全性,GCS组的DoR明显更长。与GCD一样,GCS是晚期BTC的标准治疗方案之一。
{"title":"Durvalumab plus gemcitabine-cisplatin versus S-1 plus gemcitabine-cisplatin in advanced biliary tract cancer: a comparative study","authors":"T. Satake, M. Sasaki, H. Imaoka, S. Taro, K. Inoue, T. Taira, G. Igarashi, M. Amisaki, H. Takahashi, S. Mitsunaga, M. Ikeda","doi":"10.1016/j.esmogo.2025.100265","DOIUrl":"10.1016/j.esmogo.2025.100265","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Following the TOPAZ-1 trial, chemoimmunotherapy with durvalumab plus gemcitabine and cisplatin (GCD) became the standard first-line treatment of advanced biliary tract cancer (BTC). This study aimed to compare the therapeutic efficacy of GCD and gemcitabine, cisplatin, and S-1 (GCS).</div></div><div><h3>Methods</h3><div>This single-center, retrospective study consecutively included patients with advanced BTC receiving primary treatment with GCD or GCS between November 2018 and August 2024.</div></div><div><h3>Results</h3><div>A total 265 patients with advanced BTC were included: 97 were treated with GCD and 168 were treated with GCS. Median overall survival (OS) was 17.1 months [95% confidence interval (CI) 12.7-20.6 months] in the GCD group versus 18.3 months (95% CI 15.4-20.4 months) in the GCS group, with no statistically significant difference (<em>P</em> = 0.509). Median progression-free survival (PFS) was 8.0 months (95% CI 5.9-9.6 months) in the GCD group versus 8.9 months (95% CI 7.1-11.4 months) in the GCS group (<em>P</em> = 0.077). No differences were noted in objective response rates, whereas median duration of response (DoR) was significantly longer in the GCS group (12.7 months) than that in the GCD group (7.5 months) (<em>P</em> = 0.022). Patients with <em>ARID1A</em> or <em>PIK3CA</em> alterations, or with <em>SMAD4</em> wild-type, had better OS with GCS than with GCD.</div></div><div><h3>Conclusion</h3><div>GCD and GCS provide comparable survival outcomes and safety in clinical practice, with a significantly longer DoR in the GCS group. Alongside GCD, GCS represents one of the standard treatment options for advanced BTC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100265"},"PeriodicalIF":0.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}