ESMO Gastrointestinal Oncology最新文献

{"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}

{"title":"Distinct clinicopathological and survival profiles of CLDN18.2 and PD-L1 expression in advanced gastric cancer and gastroesophageal junction adenocarcinoma","authors":"D.R. Castillo ,&nbsp;M. Guo ,&nbsp;P. Shah ,&nbsp;M. Hazeltin ,&nbsp;D. Tai ,&nbsp;F. Al-Manaseer ,&nbsp;S. Mlamba ,&nbsp;D. Perez ,&nbsp;S. Yeremian ,&nbsp;S. Guzman ,&nbsp;R. Mannan ,&nbsp;C. Crook ,&nbsp;C. Lau ,&nbsp;N. Tawar ,&nbsp;G. Brar ,&nbsp;M. Raoof ,&nbsp;Y. Woo ,&nbsp;S.P. Wu ,&nbsp;D. Li","doi":"10.1016/j.esmogo.2025.100261","DOIUrl":"10.1016/j.esmogo.2025.100261","url":null,"abstract":"<div><h3>Background</h3><div>Claudin 18.2 (CLDN18.2)-targeted therapy and immune checkpoint blockade have transformed the frontline treatment landscape of gastric and gastroesophageal junction (GC/GEJ) cancers, marking a major advance in precision oncology. However, the optimal sequencing and integration of these biomarker-driven therapies remain undefined. A comprehensive evaluation of the relationship between CLDN18.2 and programmed death-ligand 1 (PD-L1) expression, along with co-occurring genomic alterations and metastatic patterns, is critical to refine patient selection and improve survival outcomes.</div></div><div><h3>Materials and methods</h3><div>We retrospectively analyzed 70 patients with microsatellite-stable, human epidermal growth factor receptor 2 (HER2)-negative metastatic GC/GEJ adenocarcinoma treated with first-line chemoimmunotherapy. CLDN18.2 positivity was defined as ≥75% of tumor cells with moderate to strong membranous staining, and PD-L1 positivity as a combined positive score (CPS) ≥1. Molecular profiling of pretreatment tumor biopsies was carried out using a hybrid DNA/RNA sequencing panel covering 720 cancer-related genes. The incidence of key genomic alterations (<em>TP53, KRAS, CDH1, PIK3CA, RHOA, POLE, and CLDN18–ARHGAP6</em> fusion) was compared between CLDN18.2-positive and -negative tumors. Clinicopathological variables, including age, sex, race, Lauren classification, metastatic site, PD-L1 CPS, CLDN18.2 status, and receipt of hyperthermic intraperitoneal chemotherapy (HIPEC), were evaluated. Survival outcomes were estimated using the Kaplan–Meier method, and univariate and multivariate Cox regression analyses were carried out to identify prognostic factors.</div></div><div><h3>Results</h3><div>Thirty-eight tumors (54%) were CLDN18.2-positive. CLDN18.2-negative tumors were more likely to harbor <em>KRAS</em> mutations and higher PD-L1 CPS. No significant differences in overall survival (OS) or progression-free survival (PFS) were observed between CLDN18.2-positive and -negative groups. Among all covariates, metastatic burden (oligometastatic versus polymetastatic) and race were independently associated with OS. In contrast, age, sex, histology, PD-L1 CPS, and CLDN18.2 expression were not prognostic. HIPEC did not significantly improve PFS or OS compared with non-HIPEC treatment; however, a trend toward improved outcomes suggests potential benefit in selected patients, supporting further prospective evaluation.</div></div><div><h3>Conclusions</h3><div>CLDN18.2 and PD-L1 expression delineate distinct molecular and metastatic subgroups of GC/GEJ cancer. Personalized strategies integrating biomarker-driven systemic and regional therapies may enhance outcomes in this heterogeneous disease. Although HIPEC did not significantly improve survival, the observed trend warrants further validation in prospective studies.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100261"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466171","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}

{"title":"Drug dose optimization and substitutions to improve access for patients with gastrointestinal and neuroendocrine cancers","authors":"R.P. Riechelmann ,&nbsp;T.C. Felismino ,&nbsp;B. Müller ,&nbsp;R. D’Alpino Peixoto ,&nbsp;D.A. Goldstein","doi":"10.1016/j.esmogo.2025.100239","DOIUrl":"10.1016/j.esmogo.2025.100239","url":null,"abstract":"<div><div>The cost of cancer care has significantly increased, with a major cause being the high cost of new drugs, limiting their access worldwide. Drug dose optimization (DDO) and substitutions may help improve treatment access for patients residing in financially resource-limited countries. We propose and discuss these strategies for patients with gastrointestinal (GI) cancers and neuroendocrine tumors (NET) who are treated in low- and middle-income countries, considering the available scientific evidence. Overall recommendations include dose-reductions of palliative chemotherapy, avoiding colony-stimulation growth factors when unnecessary, lower doses of immune checkpoint inhibitors and paclitaxel as a substitute for nab-paclitaxel. Specific proposals by tumor type are discussed and recommended according to resource availability.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100239"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109179","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}

{"title":"Durvalumab plus gemcitabine-cisplatin versus S-1 plus gemcitabine-cisplatin in advanced biliary tract cancer: a comparative study","authors":"T. Satake,&nbsp;M. Sasaki,&nbsp;H. Imaoka,&nbsp;S. Taro,&nbsp;K. Inoue,&nbsp;T. Taira,&nbsp;G. Igarashi,&nbsp;M. Amisaki,&nbsp;H. Takahashi,&nbsp;S. Mitsunaga,&nbsp;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":"2025-12-01","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}

{"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 ,&nbsp;S. Camera ,&nbsp;S. Foti ,&nbsp;M. Persano ,&nbsp;C.M. Gullotta ,&nbsp;F. Rossari ,&nbsp;F. Vitiello ,&nbsp;L. Passeri ,&nbsp;F. Michele ,&nbsp;A. Casadei-Gardini ,&nbsp;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> &lt; 0.0001) and racial distribution (<em>P</em> &lt; 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> &lt; 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> &lt; 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}

{"title":"MDM2 amplification in advanced biliary tract cancer: something new to explore?","authors":"A. Rizzo ,&nbsp;O. Brunetti ,&nbsp;R. Massafra ,&nbsp;G. Brandi","doi":"10.1016/j.esmogo.2025.100247","DOIUrl":"10.1016/j.esmogo.2025.100247","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100247"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159275","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}

{"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 ,&nbsp;A. Vienot ,&nbsp;J.-D. Fumet ,&nbsp;A. Meurisse ,&nbsp;T. Nguyen ,&nbsp;E. Klajer ,&nbsp;A. Bouard ,&nbsp;L. Spehner ,&nbsp;F. Fein ,&nbsp;M. Stouvenot ,&nbsp;E. Dochy ,&nbsp;M. Rebucci-Peixoto ,&nbsp;H. Almotlak ,&nbsp;J. Henriquez ,&nbsp;Z. Selmani ,&nbsp;D. Vernerey ,&nbsp;E. Hervouet ,&nbsp;A. Folletet ,&nbsp;S. Kim ,&nbsp;F. Ghiringhelli ,&nbsp;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/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.</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 &gt;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}

{"title":"Clinicopathological features and outcomes for colorectal carcinomas with KRAS codon 146 mutations","authors":"R.K. Yang ,&nbsp;A. Rashid ,&nbsp;S. Roy-Chowdhuri ,&nbsp;D.S. Hong ,&nbsp;J. Bryan","doi":"10.1016/j.esmogo.2025.100244","DOIUrl":"10.1016/j.esmogo.2025.100244","url":null,"abstract":"<div><h3>Background</h3><div><em>KRAS</em>-activating mutations characterize ∼40% of colorectal carcinomas (CRCs) and predict resistance to anti-epidermal growth factor receptor therapy. Because the location of <em>KRAS</em> mutations conveys distinct biophysical consequences, we investigated whether CRCs’ clinicopathological features varied by <em>KRAS</em> mutation codon.</div></div><div><h3>Patients and methods</h3><div>CRC patients from 2018 to 2022 were identified from the United States National Cancer Database, which reports <em>KRAS</em> as wild-type versus codon 12/13/61-mutant versus codon 146-mutant. <em>KRAS</em> codon mutations were compared using multivariable logistic regression for clinicopathological features and multivariable Cox regression for overall survival (OS). Notable limitations include a lack of granular codon characterization and detailed treatment data.</div></div><div><h3>Results</h3><div>Nationally, <em>n</em> = 76 581 CRC patients were identified, 43.3% of whom were <em>KRAS</em> mutated (including <em>n</em> = 16 366 at codon 12/13/61 and <em>n</em> = 784 at codon 146). Among tumor characteristics, codon 146-mutated CRCs were less likely poorly differentiated (12.1%) and more likely moderately differentiated (80.7%) than codon 12/13/61-mutated CRCs (15.9% and 76.0%, respectively; <em>P</em> = 0.003). Additionally, codon 146-mutated CRCs less likely involved the sigmoid colon (14.4% versus 18.1% of codon 12/13/61-mutated CRCs; <em>P</em> = 0.004). <em>KRAS</em> codon 146-mutated CRCs were enriched with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) (10.1% versus 5.9% of codon 12/13/61-mutated; <em>P</em> &lt; 0.001) and were less likely concurrently <em>NRAS</em> mutant (1.5% versus 8.0% of codon 12/13/61-mutated; chi-square <em>P</em> &lt; 0.001). Adjusting for patient characteristics and treatments, no OS difference was observed between <em>KRAS</em> codon 146-mutated and 12/13/61-mutated stage IV CRCs (hazard ratio 0.97, 95% confidence interval 0.84-1.12, <em>P</em> = 0.69).</div></div><div><h3>Conclusion</h3><div>Nationally, CRCs with <em>KRAS</em> mutations at codon 146 exhibited select pathological and MSI/MMR differences—illustrating that <em>KRAS</em> mutations have codon-specific manifestations that warrant further investigation, particularly as the armamentarium of alteration-specific KRAS inhibitors grows.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100244"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268338","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}

{"title":"Treatment options for advanced small bowel adenocarcinoma: a systematic review","authors":"M. Ghidini ,&nbsp;A. Parisi ,&nbsp;I.V. Zurlo ,&nbsp;M.M. Laterza ,&nbsp;L. Gervaso ,&nbsp;A.D. Ricci ,&nbsp;A. Biasi ,&nbsp;A. Nicastro ,&nbsp;O. Garrone ,&nbsp;G. Tomasello ,&nbsp;A. Petrillo ,&nbsp;F. Petrelli","doi":"10.1016/j.esmogo.2025.100248","DOIUrl":"10.1016/j.esmogo.2025.100248","url":null,"abstract":"<div><div>Small bowel adenocarcinoma (SBA) is a rare and increasingly recognised malignancy, accounting for only 3.4% of all gastrointestinal cancers. It often presents with non-specific or late-stage symptoms, resulting in delayed diagnosis and poor prognosis. For advanced disease, treatment recommendations rely primarily on small phase II trials and retrospective series with no established standard therapy. Moreover, although SBA commonly harbours <em>KRAS</em> mutations (43%), <em>CDKN2A</em> (p16) loss, and <em>HER2/ERBB2</em> mutations (12%), no targeted biological agents have demonstrated clinical efficacy against this disease. Our systematic review was conducted to comprehensively evaluate the available evidence on systemic therapies for patients with advanced or metastatic SBA, with particular focus on treatment efficacy, safety profiles, and the potential influence of molecular biomarkers.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100248"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268339","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}

{"title":"Association between neutropenia and efficacy in patients with refractory mCRC receiving trifluridine/tipiracil + bevacizumab: post hoc analysis of the SUNLIGHT trial","authors":"G.W. Prager ,&nbsp;E. Elez ,&nbsp;M. Fakih ,&nbsp;F. Ciardiello ,&nbsp;E. Van Cutsem ,&nbsp;L. Roby ,&nbsp;W. Yao ,&nbsp;E. Choucair ,&nbsp;J. Taieb","doi":"10.1016/j.esmogo.2025.100234","DOIUrl":"10.1016/j.esmogo.2025.100234","url":null,"abstract":"<div><h3>Background</h3><div>The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared with FTD/TPI for the treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. However, the association between neutropenia and neutrophil count decrease (NCD) and efficacy outcomes in the SUNLIGHT population has not yet been assessed.</div></div><div><h3>Patients and methods</h3><div>Patients with mCRC enrolled in SUNLIGHT had received no more than two prior treatment regimens and were randomised to receive either FTD/TPI + bevacizumab or FTD/TPI. In this <em>post hoc</em> analysis, overall survival (OS) and progression-free survival (PFS) were analysed in patients with severe (grade ≥3) neutropenia/NCD and in patients with no, or non-severe, neutropenia/NCD.</div></div><div><h3>Results</h3><div>Patients treated with FTD/TPI + bevacizumab with severe neutropenia/NCD had longer OS (hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.26-0.52] <em>P</em> &lt; 0.0001) and PFS (HR 0.41 [95% CI 0.31-0.55] <em>P</em> &lt; 0.0001) than patients with non-severe or no neutropenia/NCD. Patients treated with FTD/TPI + bevacizumab had improved OS compared with patients treated with FTD/TPI in the severe neutropenia/NCD (HR 0.58 [95% CI 0.40-0.85] <em>P</em> = 0.0046) and non-severe or no neutropenia/NCD (HR 0.71 [95% CI 0.54-0.94] <em>P</em> = 0.0176) subgroups. Most cases of severe neutropenia/NCD occurred during the first two cycles of treatment, did not lead to dose reduction or interruption, and were effectively managed with or without the use of granulocyte colony-stimulating factor.</div></div><div><h3>Conclusions</h3><div>In SUNLIGHT, patients who developed severe neutropenia/NCD had improved OS and PFS in both treatment arms. Patients receiving FTD/TPI + bevacizumab had longer OS/PFS than patients receiving FTD/TPI, irrespective of the presence of severe neutropenia/NCD.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100234"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020669","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}