ESMO Gastrointestinal Oncology最新文献

{"title":"Growth differentiation factor-15 (GDF-15) in localized pancreatic adenocarcinoma treated with multiagent chemotherapy: a biomarker analysis from the NEOLAP trial (AIO-PAK-0113)","authors":"B. Kimmel ,&nbsp;S.T. Löhnert ,&nbsp;F. Wedekink ,&nbsp;M. Günther ,&nbsp;S. Ormanns ,&nbsp;I. Hartlapp ,&nbsp;J. Siveke ,&nbsp;G. Siegler ,&nbsp;S. Boeck ,&nbsp;H. Algül ,&nbsp;U. Martens ,&nbsp;F. Kullmann ,&nbsp;T. Ettrich ,&nbsp;S. Held ,&nbsp;F. Anger ,&nbsp;C.-T. Germer ,&nbsp;V. Heinemann ,&nbsp;J. Wischhusen ,&nbsp;V. Kunzmann","doi":"10.1016/j.esmogo.2025.100274","DOIUrl":"10.1016/j.esmogo.2025.100274","url":null,"abstract":"<div><h3>Background</h3><div>The prognostic and predictive role of growth differentiation factor-15 (GDF-15) in localized, non-metastatic pancreatic ductal adenocarcinoma (PDAC) has not yet been explored.</div></div><div><h3>Patients and methods</h3><div>During the prospective randomized phase II NEOLAP-1 (AIO-PAK-0113) trial for patients with therapy-naive locally advanced (borderline or unresectable) PDAC, blood (<em>n</em> = 131) and tumor tissue samples (<em>n</em> = 39) were collected. Using paired baseline and post-induction chemotherapy (ICT) samples, circulating GDF-15 (cGDF-15) levels were quantified by enzyme-linked immunosorbent assay, and local GDF-15 tumor expression (tGDF-15) was assessed by immunohistochemistry.</div></div><div><h3>Results</h3><div>Lower baseline cGDF-15 levels (≤0.8 ng/ml) were significantly associated with increased median overall survival [21.92 (95% CI 19.73-24.16) versus 12.68 [95% confidence interval (CI) 10.56-14.81] months, <em>P</em> &lt; 0.001, and significantly higher secondary R0 resection rates (36.5% versus 13.9%, <em>P</em> = 0.0051). In contrast to CA 19-9, cGDF-15 levels significantly increased after ICT [median 1.0 ng/ml [interquartile range (IQR) 0.62-1.5 ng/ml] at baseline versus median 2.37 ng/ml (IQR 1.32-4.43 ng/ml) at week 16], especially after treatment using platinum-based agents. In initial tumor specimens, GDF-15 expression was rare and predominantly confined to tumor cells. tGDF-15 correlated with high cGDF-15 levels at baseline [median 1.8 ng/ml (1.13-2.34 ng/ml) in positive tumor specimens, versus 0.76 ng/ml (0.55-1.17 ng/ml) in negative tumor specimens; <em>P</em> = 0.0087]. Similarly to cGDF-15, tGDF-15 expression increased after ICT (from 10% to 41% positive tumor specimens).</div></div><div><h3>Conclusions</h3><div>High cGDF-15 levels at baseline are a negative prognostic and predictive biomarker in localized, non-metastatic PDAC. Considering that GDF-15 is further up-regulated by neoadjuvant multiagent chemotherapy, our data, together with recent findings on clinical effects of GDF-15, provide a strong rationale for upfront therapeutic GDF-15 blockade in localized PDAC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100274"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791900","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":"Impact of diabetes mellitus on treatment efficacy in patients with advanced pancreatic cancer: the Italian, multicenter, observational PANCAKE study","authors":"P. Andena ,&nbsp;G. Tine ,&nbsp;F. Nichetti ,&nbsp;A. Pretta ,&nbsp;L. Bartalini ,&nbsp;S. Ljevar ,&nbsp;A. Michelotti ,&nbsp;L. Salvatore ,&nbsp;M. Prisciandaro ,&nbsp;A. Franza ,&nbsp;G. Grelli ,&nbsp;P. Ziranu ,&nbsp;M. Bensi ,&nbsp;V. Mazzaferro ,&nbsp;J. Coppa ,&nbsp;C. Sciortino ,&nbsp;G. Zapelloni ,&nbsp;C. Pircher ,&nbsp;S.K. Garattini ,&nbsp;C. Vivaldi ,&nbsp;M. Niger","doi":"10.1016/j.esmogo.2025.100276","DOIUrl":"10.1016/j.esmogo.2025.100276","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) is a known risk factor for pancreatic ductal adenocarcinoma (PDAC). Preclinical evidence suggests higher glucose levels may enhance chemotherapy injury to PDAC cells. Clinical evidence of DM’s impact in patients with PDAC receiving palliative treatment remains conflicting, however.</div></div><div><h3>Materials and methods</h3><div>PANCAKE, an Italian multicenter observational study, assessed the impact of DM and blood glucose levels on progression-free survival during first-line treatment and overall survival (OS) in patients with advanced PDAC.</div></div><div><h3>Results</h3><div>Among 663 patients with available baseline and on-treatment glycemic values, DM was confirmed in 193 patients (29.1%). Pre-existing DM was associated with a modest but significant OS benefit [median OS 11.6 versus 10.3 months, adjusted hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.67-0.99; <em>P</em> = 0.036]. This benefit was significantly associated with the chemotherapy regimen: it was observed only in patients treated with first-line gemcitabine–nab-paclitaxel, but not with FOLFIRINOX. A longitudinal, Bayesian joint modelling approach accounting for the concomitant use of glucose-lowering medications confirmed a statistically significant, but clinically modest prognostic effect of glycemic trends, as a 10 mg/dl-point increase from baseline blood glucose values resulted associated with a 4% reduction in the risk of death (HR for OS 0.9967, 95% CI 0.9939-0.9995).</div></div><div><h3>Conclusions</h3><div>DM and higher blood glucose levels show a statistically significant, though clinically modest, impact on the OS of patients affected by advanced PDAC, which may be differential according to the chemotherapy regimen. This evidence lays the foundations to guide future studies on pharmacological and dietary approaches targeting tumor metabolism in this setting.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100276"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791901","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":"DESTINY-Gastric05 phase III trial of first-line trastuzumab deruxtecan, chemotherapy, and pembrolizumab in HER2-positive gastric or gastroesophageal junction cancer","authors":"Y.Y. Janjigian ,&nbsp;E. Smyth ,&nbsp;L. Shen ,&nbsp;J. Lee ,&nbsp;P.M. Hoff ,&nbsp;S. Lonardi ,&nbsp;D. Barrios ,&nbsp;K. Kobayashi ,&nbsp;Y. Okuda ,&nbsp;T. Kamio ,&nbsp;K. Shitara","doi":"10.1016/j.esmogo.2025.100294","DOIUrl":"10.1016/j.esmogo.2025.100294","url":null,"abstract":"<div><h3>Background</h3><div>Gastric or gastroesophageal junction (GEJ) cancers are usually diagnosed at advanced stages with poor prognoses and 5-year survival rates. Standard-of-care first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic disease is chemotherapy and trastuzumab, plus pembrolizumab for programmed death-ligand 1 (PD-L1)-positive [combined positive score (CPS) ≥1] tumors. Trastuzumab deruxtecan (T-DXd) 6.4 mg/kg monotherapy is approved as second-line treatment for patients with HER2-positive gastric or GEJ cancer. DESTINY-Gastric03 (NCT04379596) showed that first-line T-DXd 5.4 mg/kg plus chemotherapy with or without pembrolizumab in the advanced setting had manageable safety and promising efficacy in HER2-positive gastric or GEJ cancer.</div></div><div><h3>Aim</h3><div>To investigate a first-line T-DXd plus platinum-free chemotherapy with pembrolizumab treatment approach for patients with HER2-positive gastric or GEJ cancer.</div></div><div><h3>Trial design</h3><div>DESTINY-Gastric05 (NCT06731478) is a global, multicenter, open-label, randomized, phase III trial to evaluate the efficacy and safety of first-line T-DXd 5.4 mg/kg plus 5-fluorouracil or capecitabine and pembrolizumab versus platinum-based chemotherapy with trastuzumab and pembrolizumab in patients with unresectable, locally advanced or metastatic, centrally confirmed HER2-positive (immunohistochemistry 3+ or immunohistochemistry 2+/<em>in situ</em> hybridization positive) gastric or GEJ cancer with a PD-L1 CPS ≥1. An exploratory cohort is to evaluate T-DXd plus 5-fluorouracil or capecitabine in patients with PD-L1 CPS &lt;1.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100294"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038192","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 use in patients with unresectable hepatocellular carcinoma: analyses of subgroups of special interest in the observational REFINE study","authors":"Y.J. Kim ,&nbsp;P. Merle ,&nbsp;R.S. Finn ,&nbsp;H.-J. Klümpen ,&nbsp;H.Y. Lim ,&nbsp;M. Ikeda ,&nbsp;A. Granito ,&nbsp;G. Masi ,&nbsp;R. Gerolami ,&nbsp;M. Pinter ,&nbsp;S. Babajanyan ,&nbsp;P. Twumasi-Ankrah ,&nbsp;M. Ghadessi ,&nbsp;K. Ozgurdal ,&nbsp;S. Qin","doi":"10.1016/j.esmogo.2025.100292","DOIUrl":"10.1016/j.esmogo.2025.100292","url":null,"abstract":"<div><h3>Background</h3><div>The findings of the prospective, real-world REFINE trial supported the safety and efficacy of regorafenib reported in the phase III RESORCE study, in a broader population of patients with unresectable hepatocellular carcinoma (HCC). This <em>post hoc</em> analysis evaluated patient subgroups based on liver function, liver cancer stage, and prior treatment.</div></div><div><h3>Patients and methods</h3><div>Patients were analyzed by subgroups based on liver function [Child–Pugh (CP)–B/B7], prior treatment [prior orthotopic liver transplant (pOLT), transarterial chemoembolization (TACE)/transarterial radioembolization (TARE)], and Barcelona Clinic Liver Cancer (BCLC) stage. The primary objective was to evaluate the safety of regorafenib. Secondary objectives included effectiveness endpoints of overall survival (OS) and duration of treatment. All analyses were descriptive with no adjustment for confounders.</div></div><div><h3>Results</h3><div>A total of 1005 patients were evaluable (overall population). In patients with CP–B (<em>n</em> = 123) compared with the overall population, the incidence of grade ≥3 (28% versus 27%) and serious drug-related treatment-emergent adverse events (TEAEs) was similar (11% versus 9%), whereas TEAEs leading to permanent discontinuation of regorafenib were more common (28% versus 16%). In patients with prior TACE (<em>n</em> = 584), the incidence of TEAEs was generally similar to patients without prior TACE (<em>n</em> = 421) and the overall population (92%, 91%, and 92%, respectively). Median OS was 12.3-19.3 months across all subgroups except CP–B/B7 (6.4/6.7 months).</div></div><div><h3>Conclusions</h3><div>This subgroup analysis of REFINE provides further evidence on the safety and effectiveness of regorafenib demonstrated in RESORCE, in underrepresented subgroups (CP–B, BCLC stage B/C, pOLT) and in those previously treated with TACE/TARE.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100292"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038191","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":"Comparative outcomes with low-dose and standard-dose immune checkpoint inhibitors in microsatellite stable advanced gastric/gastroesophageal adenocarcinoma☆","authors":"A. Ramaswamy ,&nbsp;V. Shenoy ,&nbsp;A. Bahl ,&nbsp;A. Rauthan ,&nbsp;V.M. Krishna ,&nbsp;V. Talwar ,&nbsp;V. Agarwala ,&nbsp;A. Kapoor ,&nbsp;R. Pinninti ,&nbsp;M. Sharma ,&nbsp;S.J. Rajappa ,&nbsp;N. Rohatgi ,&nbsp;A. Khan ,&nbsp;A. Jain ,&nbsp;U. Batra ,&nbsp;R.K. Kaushal ,&nbsp;M.V. Chandrakanth ,&nbsp;B. Sansar ,&nbsp;A. Gupta ,&nbsp;P. Bhargava ,&nbsp;V. Ostwal","doi":"10.1016/j.esmogo.2026.100302","DOIUrl":"10.1016/j.esmogo.2026.100302","url":null,"abstract":"<div><h3>Background</h3><div>The combination of chemotherapy and immune checkpoint inhibitors (ICIs) is usually considered standard in advanced gastric/gastroesophageal adenocarcinoma (GC) with combined positive score (CPS) 6≥5.</div></div><div><h3>Methods</h3><div>Data of patients with microsatellite stable advanced GCs receiving chemotherapy combined with ICIs between August 2021 and February 2024 were collated from eight institutions in India. The primary endpoint was to compare median overall survival between patients receiving standard-dose ICIs (SD-ICIs) and low-dose ICIs (LD-ICIs) as first-line treatment when CPS ≥5.</div></div><div><h3>Results</h3><div>Data of 288 patients were collated, of whom 256 patients had adequate data for analysis. A CPS ≥5 was seen in 161 patients (63%). Nivolumab was used in a majority of patients (75%). After propensity matching for age, 124 patients (62 patients receiving LD-ICIs and SD-ICIs, each) were available for analysis. With a median follow-up of 9.8 months [95% confidence interval (CI) 7.6-12.1 months], there was no difference in median overall survival between patients receiving LD-ICIs and SD-ICIs (16.8 months, 95% CI 7.59-25.97 months versus 16.1 months, 95% CI 10.3 months-not reached, <em>P</em> = 0.95). There was also no difference in median time to treatment failure between patients receiving LD-ICIs and SD-ICIs (6.83 months, 95% CI 4.65-9.01 months versus 7.78 months, 95% CI 6.04-9.56 months, <em>P</em> = 0.31).</div></div><div><h3>Conclusions</h3><div>LD-ICIs can be evaluated in combination with chemotherapy in patients with advanced GC and CPS ≥5 where standard dosing is not feasible, pending evidence from prospective trials.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100302"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188602","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":"Impact of nutritional risk screening on outcomes of first-line treatment in metastatic esophagogastric adenocarcinoma: a secondary analysis of the AIO-MATEO trial","authors":"R. Stelmach ,&nbsp;S. Lorenzen ,&nbsp;T.J. Ettrich ,&nbsp;F.R. Longo ,&nbsp;B. Chibaudel ,&nbsp;R. Greil ,&nbsp;M. Perwög ,&nbsp;J. Larcher-Steiner ,&nbsp;D. Jäger ,&nbsp;F. Lordick ,&nbsp;G. Stocker ,&nbsp;G.M. Haag","doi":"10.1016/j.esmogo.2025.100297","DOIUrl":"10.1016/j.esmogo.2025.100297","url":null,"abstract":"<div><h3>Background</h3><div>Malnutrition is common in patients with metastatic esophagogastric adenocarcinoma (EGA). However, the prognostic impact of nutritional risk screening (NRS) in advanced EGA remains underexplored. This preplanned analysis of the phase II AIO-MATEO trial evaluated the impact of NRS on clinical outcomes for patients with advanced EGA.</div></div><div><h3>Patients and methods</h3><div>Patients enrolled in the MATEO trial (exploring S-1 maintenance therapy) with an available baseline NRS before induction chemotherapy were included. Patients were stratified by their baseline NRS score (&lt;3 versus ≥3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier and Cox regression methods.</div></div><div><h3>Results</h3><div>Of the 136 patients, 86 had an NRS score &lt;3 and 50 had an NRS score ≥3 at baseline. Baseline median European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) global health score was lower for the NRS ≥3 group (37.5 versus 58.3). Nutritional interventions were more frequent in the NRS ≥3 group (45.8% versus 10.6%; <em>P</em> &lt; 0.001). Patients with NRS ≥3 had inferior median PFS (4.9 months versus 6.9 months; <em>P</em> = 0.025) and OS (8.2 months versus 13.2 months; <em>P</em> = 0.003). Patients whose NRS score improved during induction chemotherapy showed superior median PFS (7.4 months versus 4.1 months; <em>P</em> = 0.085) and OS (20.1 months versus 8.0 months; <em>P</em> = 0.054) compared with those without improvement. No significant differences in overall toxicity were observed.</div></div><div><h3>Conclusions</h3><div>Baseline NRS is a significant predictor of outcome in patients with metastatic EGA. Our findings underscore the importance of routinely assessing the nutritional status of patients with metastatic EGA and intervening early.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100297"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078108","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":"Highlights in oesophagogastric cancers from ESMO congress 2025","authors":"A. Petrillo ,&nbsp;F. Pietrantonio ,&nbsp;T. Fleitas-Kanonnikoff","doi":"10.1016/j.esmogo.2025.100275","DOIUrl":"10.1016/j.esmogo.2025.100275","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100275"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791902","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":"Real-world treatment outcomes for pancreatic neuroendocrine tumours: a single tertiary referral institute experience","authors":"L.L. Chan ,&nbsp;A.C.Y. Lam ,&nbsp;H.H.W. Leung ,&nbsp;S.H. Chok ,&nbsp;S.Y.W. Liu ,&nbsp;J.W.C. Kung ,&nbsp;R. Ozaki ,&nbsp;A.P.S. Kong ,&nbsp;R.C.W. Ma ,&nbsp;S.L. Chan","doi":"10.1016/j.esmogo.2025.100293","DOIUrl":"10.1016/j.esmogo.2025.100293","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic neuroendocrine tumours (PNETs) are rare neoplasms of the pancreas. Real-world treatment outcomes in Asia are seldom reported. The aim of this study was to provide the real-world treatment outcomes of PNETs at a single tertiary cancer centre in Hong Kong over an 18-year period.</div></div><div><h3>Materials and methods</h3><div>This was a retrospective cohort study that recruits patients with local or metastatic PNETs treated at Prince of Wales Hospital, Hong Kong between 2005 and 2023. Five-year overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS) of the surgical cohort, and survival outcomes in patients with metastatic disease were summarized.</div></div><div><h3>Results</h3><div>A total of 98 patients were recruited (median age: 59 years, 51% male). Among them, 18 patients (18.4%) had functioning tumours, of which majority were insulinoma (72.2%). Most tumours (64.8%) were classified as grade 1 disease. More than 80% of patients had early-stage disease on presentation, with only 14 patients presented with stage IV disease. Five-year OS for the entire cohort was 88.4% and the 5-year PFS was 73.7%. Older age [hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.00-1.13, <em>P</em> = 0.04] and larger tumour size (HR 1.20, 95% CI 1.00-1.44, <em>P</em> = 0.05) were associated with worse OS, whereas patients with metastatic disease had a shorter PFS (HR 7.95, 95% CI 2.55-24.8, <em>P</em> &lt; 0.001). In the cohort treated with curative surgery, metastatic disease (HR 7.49, 95% CI 1.40-40.0, <em>P</em> = 0.018) and tumour grade (HR 8.03, 95% CI 1.58-40.8, <em>P</em> = 0.012) were associated with worse RFS. Microscopic margin involvement did not influence RFS in patients treated with curative surgery. In the 20 patients who received systemic therapy, everolimus showed a trend towards improved PFS compared with chemotherapy (5-year PFS: 46.9% versus 16.7%).</div></div><div><h3>Conclusion</h3><div>Patients with PNETs in Hong Kong have early presentation and excellent prognosis with most patients being eligible for curative surgery reaching 90% of 5-year OS.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100293"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078110","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":"Impact of claudin 18.2 expression on the efficacy of trastuzumab deruxtecan in patients with HER2-positive gastric or gastroesophageal junction cancer","authors":"D. Okemoto ,&nbsp;I. Nakayama ,&nbsp;A. Jubashi ,&nbsp;N. Sakamoto ,&nbsp;M. Okunaka ,&nbsp;Y. Matsubara ,&nbsp;Y. Miyashita ,&nbsp;A. Kobayashi ,&nbsp;U. Okazaki ,&nbsp;K. Yamamoto ,&nbsp;K. Seguchi ,&nbsp;T. Hosokai ,&nbsp;T. Ogura ,&nbsp;S. Mishima ,&nbsp;D. Kotani ,&nbsp;A. Kawazoe ,&nbsp;T. Hashimoto ,&nbsp;Y. Kuboki ,&nbsp;H. Bando ,&nbsp;T. Kojima ,&nbsp;K. Shitara","doi":"10.1016/j.esmogo.2025.100300","DOIUrl":"10.1016/j.esmogo.2025.100300","url":null,"abstract":"<div><h3>Background</h3><div>Human epidermal growth factor receptor 2 (HER2) and claudin 18.2 (CLDN18.2) are key therapeutic targets in metastatic gastric and gastroesophageal junction cancer (mGC/GEJC). Trastuzumab deruxtecan (T-DXd) is standard care for previously treated HER2-positive mGC/GEJC, but the prognostic impact of CLDN18.2 remains unclear.</div></div><div><h3>Patients and methods</h3><div>We retrospectively reviewed patients with HER2-positive mGC/GEJC treated with T-DXd at National Cancer Center Hospital East until February 2025. T-DXd outcomes were compared between CLDN18.2-positive (≥2+ in ≥75% of tumor cells) and -negative patients in two cohorts: those with HER2 positivity before first-line therapy (overall cohort) and those maintaining HER2 positivity immediately before T-DXd (remaining HER2 cohort). CLDN18.2 expression was evaluated at any time before T-DXd administration.</div></div><div><h3>Results</h3><div>Eighty-seven patients were included in the overall cohort and 30 in the remaining HER2 cohort. In the overall cohort, progression-free survival (PFS) was shorter in CLDN18.2-positive patients [3.9 versus 5.3 months; hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.04-3.34, <em>P</em> = 0.036], with an adjusted HR of 1.82 (95% CI 1.02-3.28, <em>P</em> = 0.047). Overall survival (OS) showed a shorter trend (8.6 versus 11.2 months, HR 1.36, 95% CI 0.76-2.45, <em>P</em> = 0.30). In the remaining HER2 cohort, CLDN18.2-positive patients had shorter PFS (3.2 versus 8.0 months, HR 3.40, 95% CI 1.38-8.40, <em>P</em> = 0.008) and OS (7.1 versus 12.9 months, HR 2.44, 95% CI 1.04-5.74, <em>P</em> = 0.041).</div></div><div><h3>Conclusions</h3><div>CLDN18.2 positivity may attenuate the efficacy of T-DXd in HER2-positive mGC/GEJC, supporting the rationale for dual blockade of CLDN18.2 and HER2.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100300"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078107","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":"BevRam-GC01 study protocol: a phase I trial of bevacizumab plus ramucirumab and paclitaxel in advanced gastric cancer","authors":"T. Wakatsuki ,&nbsp;T. Mashima ,&nbsp;N. Miyazaki ,&nbsp;H. Osumi ,&nbsp;S. Fukuoka ,&nbsp;A. Ooki ,&nbsp;K. Shimozaki ,&nbsp;M. Ogura ,&nbsp;K. Yoshino ,&nbsp;S. Udagawa ,&nbsp;E. Shinozaki ,&nbsp;K. Chin ,&nbsp;N. Ishida ,&nbsp;H. Seimiya ,&nbsp;K. Yamaguchi","doi":"10.1016/j.esmogo.2025.100299","DOIUrl":"10.1016/j.esmogo.2025.100299","url":null,"abstract":"<div><h3>Background</h3><div>Plasma vascular endothelial growth factor-A (VEGF-A) concentrations markedly increased immediately after ramucirumab administration, and the high VEGF-A concentrations were significantly associated with worse outcomes in advanced gastric cancer. In a preclinical study, combination therapy with anti-VEGF-A and anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibodies showed superior tumor suppression compared with monotherapy, suggesting dual VEGF-A/VEGFR2 blockade may be a promising therapeutic strategy.</div></div><div><h3>Design</h3><div>The BevRam-GC01 trial is a phase I trial evaluating the tolerability and safety of bevacizumab biosimilar (5 or 10 mg/kg) plus ramucirumab (8 mg/kg) and paclitaxel (80 mg/m²) in patients with advanced gastric cancer refractory to first-line fluoropyrimidine–platinum chemotherapy. The study includes a safety part and an expansion part, in which, after confirming tolerability, patients will be randomized into three arms, including a control group, to obtain proof of concept and determine the optimal BEV-BS dose. Primary endpoints are dose-limiting toxicities in the safety part and adverse events in the expansion part. Key secondary endpoints include objective response rate and day 8 free VEGF-A suppression rate. Biomarker analysis will clarify the synergistic and complementary effects of anti-VEGFR2 and anti-VEGF-A antibodies on tumor biology, including angiogenesis, proliferation, and antitumor immunity, through multi-omics analysis and immune monitoring.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100299"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188607","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}