ESMO Open最新文献

{"title":"Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival☆","authors":"J. Crown ,&nbsp;D. Stroyakovskii ,&nbsp;D.A. Yardley ,&nbsp;C.-S. Huang ,&nbsp;P.A. Fasching ,&nbsp;A. Bardia ,&nbsp;S. Chia ,&nbsp;S.-A. Im ,&nbsp;M. Martin ,&nbsp;B. Xu ,&nbsp;C.H. Barrios ,&nbsp;M. Untch ,&nbsp;R. Moroose ,&nbsp;S.A. Hurvitz ,&nbsp;G.N. Hortobagyi ,&nbsp;D.J. Slamon ,&nbsp;F. Visco ,&nbsp;G. Spera ,&nbsp;J.P. Zarate ,&nbsp;D. Halligan ,&nbsp;S. Loi","doi":"10.1016/j.esmoop.2025.105858","DOIUrl":"10.1016/j.esmoop.2025.105858","url":null,"abstract":"<div><h3>Background</h3><div>At the primary efficacy analysis of the NATALEE phase III trial, ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) demonstrated a statistically significant improvement in invasive disease-free survival (iDFS) versus NSAI alone in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC). Continued follow-up of efficacy outcomes is important in assessing the durability of treatment benefit. We report 5-year estimates of efficacy outcomes, including an udpated analysis of overall survival (OS).</div></div><div><h3>Patients and methods</h3><div>Eligible patients included pre/postmenopausal women and men with HR-positive/HER2-negative EBC and anatomic stage IIA (N1 or N0 with high-risk factors), IIB, or III disease. Patients were randomized 1 : 1 to ribociclib 400 mg/day (3 weeks on/1 week off for 3 years) + NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 5 years) or NSAI alone. Premenopausal women and men received goserelin. The primary endpoint was iDFS, and secondary/exploratory endpoints included distant disease-free survival, recurrence-free survival, distant recurrence-free survival, and OS.</div></div><div><h3>Results</h3><div>With a median iDFS follow-up of 55.4 months, ribociclib + NSAI demonstrated persistent iDFS benefit versus NSAI alone [hazard ratio 0.716, 95% confidence interval (CI) 0.618-0.829, nominal one-sided log-rank <em>P &lt;</em> 0.0001]. Absolute iDFS improvement between treatment arms increased from the 3- (Δ2.7%) to the 5-year (Δ4.5%) time points. Persistent benefit over time was also observed across subgroups [including N0 patients (hazard ratio 0.606, 95% CI 0.372-0.986)] and secondary/exploratory endpoints. As OS continues to mature, numerical improvement in favor of ribociclib was observed (hazard ratio 0.800, 95% CI 0.637-1.003, nominal one-sided log-rank <em>P</em> = 0.026).</div></div><div><h3>Conclusions</h3><div>This prespecified 5-year follow-up of efficacy outcomes from NATALEE demonstrated that ribociclib + NSAI continued to reduce the risk of recurrence beyond the 3-year treatment window, supporting its use as adjuvant therapy in patients with HR-positive/HER2-negative EBC. An ongoing positive trend for improved OS in favor of ribociclib + NSAI was observed.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105858"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MOVIE phase II trial of tremelimumab plus durvalumab combined with metronomic oral vinorelbine in patients with head and neck cancer","authors":"E. Borcoman ,&nbsp;A. Hervieu ,&nbsp;C. Cropet ,&nbsp;E. Coquan ,&nbsp;J. Guigay ,&nbsp;F. Rolland ,&nbsp;M. Bernadach ,&nbsp;E. Charafe ,&nbsp;F. Legrand ,&nbsp;E. Dassé ,&nbsp;C. Le Tourneau ,&nbsp;A. Gonçalves","doi":"10.1016/j.esmoop.2025.105840","DOIUrl":"10.1016/j.esmoop.2025.105840","url":null,"abstract":"<div><h3>Background</h3><div>Treatment options for advanced solid tumors are limited. In recent years, anti-programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy as monotherapy has shown significant efficacy, albeit in a limited subset of patients. In the MOVIE trial, metronomic chemotherapy was combined with two immune checkpoint inhibitors (ICIs) to improve clinical outcomes in patients with advanced solid tumors.</div></div><div><h3>Patients and methods</h3><div>MOVIE was a phase I/II French, multicenter, open-label, nonrandomized study with a Bayesian design that evaluated the antitumor activity and safety of metronomic vinorelbine associated with durvalumab plus tremelimumab. Here, we report on the cohort of patients with head and neck squamous cell carcinoma (HNSCC) from the MOVIE phase II study. Patients were aged ≥18 years with histologically confirmed recurrent or metastatic HNSCC, resistant to conventional therapies, and presented a measurable disease according to RECIST version 1.1. They received oral vinorelbine 40 mg three times a week, and durvalumab 1500 mg plus tremelimumab 75 mg via intravenous infusion on day 1 of 28-day cycles, for a maximum of four cycles of tremelimumab. The primary endpoint was the clinical benefit rate (CBR), defined as the rate of complete response (CR), partial response (PR), or stable disease (SD) lasting at least 24 weeks.</div></div><div><h3>Results</h3><div>Fifteen HNSCC patients were included between May 2019 and October 2020. The mean estimated CBR according to a noninformative prior distribution was 23.5% (95% credible interval 7.3-45.6). One patient achieved CR, 1 PR, and 1 SD &gt; 24 weeks, leading to an objective response rate of 14.3%. The median progression-free survival was 1.8 months (95% confidence interval 1.0-1.9 months), and the median overall survival was 8 months (95% confidence interval 2.5-12.7 months). The most common vinorelbine-related grade ≥3 adverse events were anemia (<em>n</em> = 2, 13%) and neutropenia (<em>n</em> = 3, 20%). The most common ICI-related grade ≥3 adverse events were anemia (<em>n</em> = 1) and hypokalemia (<em>n</em> = 1). There were no treatment interruptions for toxicity and no treatment-related deaths.</div></div><div><h3>Conclusions</h3><div>Metronomic vinorelbine in combination with dual durvalumab plus tremelimumab immunotherapy had only moderate activity in pretreated advanced HNSCC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105840"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second-line 5-FU plus nanoliposomal irinotecan versus FOLFOX/XELOX in metastatic pancreatic cancer after gemcitabine–nab-paclitaxel failure: a propensity score-matched analysis","authors":"G. Trovato ,&nbsp;D. Rossini ,&nbsp;A. Guidolin ,&nbsp;Y.-Y. Su ,&nbsp;Y.-S. Shan ,&nbsp;N.-J. Chiang ,&nbsp;W.-C. Chou ,&nbsp;L.-Y. Bai ,&nbsp;C. Bagalà ,&nbsp;M. Bensi ,&nbsp;M. Niger ,&nbsp;S. Marchesi ,&nbsp;S.K. Garattini ,&nbsp;A. Michelotti ,&nbsp;A. Pretta ,&nbsp;M. Scartozzi ,&nbsp;C. Vivaldi ,&nbsp;L. Bartalini ,&nbsp;L. Procaccio ,&nbsp;F. Bergamo ,&nbsp;G. Tortora","doi":"10.1016/j.esmoop.2025.105874","DOIUrl":"10.1016/j.esmoop.2025.105874","url":null,"abstract":"<div><h3>Background</h3><div>There is limited evidence comparing second-line therapies following gemcitabine plus nab-paclitaxel (GemNab) in metastatic pancreatic ductal adenocarcinoma (PDAC). This study aimed to compare the effectiveness and safety of 5-fluorouracil plus nanoliposomal irinotecan (5-FU + Nal-IRI) versus oxaliplatin-based regimens (FOLFOX/XELOX) in this setting.</div></div><div><h3>Patients and methods</h3><div>We retrospectively analyzed 445 patients with metastatic PDAC progressing after first-line GemNab, treated across 12 centers in Italy and Asia (2014-2024). Patients received either 5-FU + Nal-IRI (<em>n</em> = 180) or FOLFOX/XELOX (<em>n</em> = 265) as second-line therapy. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and safety. Exact propensity score matching was carried out to reduce baseline imbalances.</div></div><div><h3>Results</h3><div>In the matched cohort, median OS was 7.2 months [95% confidence interval (CI) 5.8-8.4 months] for 5-FU + Nal-IRI and 5.8 months (95% CI 4.1-6.8 months) for FOLFOX/XELOX [hazard ratio (HR) 0.74, 95% CI 0.58-0.95, <em>P</em> = 0.015], and median PFS was 3.0 months (95% CI 2.5-3.6 months) versus 2.5 months (95% CI 2.2-2.9 months), respectively (HR 0.75, 95% CI 0.61-0.91, <em>P</em> = 0.0048). ORR was similar (9% versus 10%, <em>P</em> = 0.79). Grade 3-4 adverse events were more frequent with 5-FU + Nal-IRI (31.1% versus 9.4%), particularly anemia (13.9% versus 1.7%) and diarrhea (5.6% versus 1.2%). FOLFOX/XELOX was associated with higher rates of any-grade thrombocytopenia and peripheral neuropathy.</div></div><div><h3>Conclusions</h3><div>5-FU + Nal-IRI showed a modest yet statistically significant survival advantage compared with FOLFOX/XELOX in patients with metastatic PDAC previously treated with GemNab, despite being associated with a higher incidence of adverse events. None the less, the selection of second-line therapy should be guided by a balanced evaluation of both efficacy and toxicity profiles.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105874"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing [18F]FDG–positron emission tomography and breast magnetic resonance imaging to predict pathological complete response and 3-year invasive disease-free survival in HER2-positive early breast cancer patients: an unplanned exploratory analysis of the PHERGain trial☆","authors":"J.J. García-Mosquera ,&nbsp;J.M. Pérez-García ,&nbsp;M. Ruiz-Borrego ,&nbsp;A. Stradella ,&nbsp;B. Bermejo ,&nbsp;S. Escrivá-de-Romaní ,&nbsp;L. Calvo Martínez ,&nbsp;G. Gebhart ,&nbsp;K. Kerrou ,&nbsp;M. Gion ,&nbsp;G. Antonarelli ,&nbsp;S. Santasusagna Canal ,&nbsp;J. Rodríguez-Morato ,&nbsp;L. Mina ,&nbsp;M. Sampayo-Cordero ,&nbsp;A. Llombart-Cussac ,&nbsp;J. Cortés","doi":"10.1016/j.esmoop.2025.105875","DOIUrl":"10.1016/j.esmoop.2025.105875","url":null,"abstract":"<div><h3>Background</h3><div>The PHERGain trial demonstrated that an [¹⁸F]2-fluoro-2-deoxy-<span>d</span>-glucose ([¹⁸F]FDG)–positron emission tomography (PET)-based, pathological complete response (pCR)-adapted strategy could be safely utilized to avoid chemotherapy (CT) in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) receiving neoadjuvant dual anti-HER2 blockade [trastuzumab and pertuzumab (HP)]. Due to the limited availability of [¹⁸F]FDG–PET, this study evaluated breast magnetic resonance imaging (MRI) as an alternative for early treatment response assessment.</div></div><div><h3>Patients and methods</h3><div>Group B patients (<em>n</em> = 285) initially received two cycles of HP, with subsequent CT introduction if [¹⁸F]FDG–PET showed no response. [¹⁸F]FDG–PET and MRI were conducted before randomization and after two cycles (early). An additional MRI was carried out before surgery (late). Concordance between [¹⁸F]FDG–PET, MRI reduction, and MRI response by RECIST v.1.1 was evaluated, along with accuracy to predict pCR and 3-year invasive disease-free survival (iDFS) rates.</div></div><div><h3>Results</h3><div>Early imaging assessment showed good accuracy (78.2%) between [¹⁸F]FDG–PET and breast MRI tumor reduction (any shrinkage), but not when applying RECIST v.1.1 response criteria (≥30% decrease in the sum of diameters of target lesions). There were higher pCR rates in [¹⁸F]FDG–PET responders with early MRI reduction (39.0% versus 29.6% if no reduction) or MRI response (44.0% versus 30.4% if no response). [¹⁸F]FDG–PET non-responders without MRI reduction had the lowest pCR (21.7%) and 3-year iDFS (75.3%) rates despite receiving CT. Among [¹⁸F]FDG–PET responders, early MRI complete responses (CRs) were uncommon, but extending CT-free treatment increased early MRI CR (9.3%-31.7%) and objective response rates (55.1%-70.0%). Late MRI CR predicted pCR better in hormone receptor (HR)-negative than in HR-positive tumors (positive predictive value: 85.5% versus 61.5%).</div></div><div><h3>Conclusions</h3><div>Although [¹⁸F]FDG–PET is the recommended imaging technique for guiding treatment in HER2-positive EBC patients following the PHERGain strategy, this unplanned analysis suggests that tumor shrinkage assessed by breast MRI could be a viable alternative for adaptive strategies in settings where [¹⁸F]FDG–PET is not available.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105875"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR2-IIIc isoform detection reveals prognostic prevalence and a functional link to mesenchymal transition in gastric and gastroesophageal junction cancer","authors":"T. Hashimoto ,&nbsp;N. Iida ,&nbsp;S. Kadowaki ,&nbsp;A. Makiyama ,&nbsp;N. Machida ,&nbsp;N. Takahashi ,&nbsp;S. Boku ,&nbsp;T. Kudo ,&nbsp;E. Oki ,&nbsp;K. Ohtsubo ,&nbsp;T. Kawakami ,&nbsp;N. Okano ,&nbsp;Y. Komatsu ,&nbsp;S. Yuki ,&nbsp;N. Sakamoto ,&nbsp;T. Kuwata ,&nbsp;R. Yamashita ,&nbsp;M. Amisaki ,&nbsp;T. Shibuki ,&nbsp;M. Imai ,&nbsp;T. Yoshino","doi":"10.1016/j.esmoop.2025.105851","DOIUrl":"10.1016/j.esmoop.2025.105851","url":null,"abstract":"<div><h3>Background</h3><div>Fibroblast growth factor receptor 2 (FGFR2), a therapeutic target for advanced gastric and gastroesophageal junction cancers (GC/GEJCs), exists as two functionally distinct isoforms: FGFR2-IIIb and FGFR2-IIIc. We investigated the clinical significance of FGFR2 splice variant distribution in advanced GC/GEJCs and its implications for therapeutic targeting.</div></div><div><h3>Patients and methods</h3><div>Whole-transcriptome sequencing was carried out on 235 patients with advanced GC/GEJCs enrolled in MONSTAR-SCREEN-2 (UMIN000043899). <em>FGFR2-IIIc</em> proportion was quantified using splice junction analysis, and its association with clinical outcomes was evaluated through survival analysis, comprehensive molecular profiling, and longitudinal assessment of treatment-induced isoform dynamics.</div></div><div><h3>Results</h3><div>Among 209 patients with detectable <em>FGFR2</em> expression, high-proportion <em>FGFR2-IIIc</em> (&gt;0.28) was associated with significantly shorter overall survival compared with low-proportion <em>FGFR2-IIIc</em> (median 9.59 versus 16.0 months, hazard ratio 2.08, 95% confidence interval 1.33-3.26, <em>P</em> &lt; 0.001). Multivariable Cox regression confirmed <em>FGFR2-IIIc</em> proportion as an independent predictor of poor prognosis (<em>P</em> = 0.008), superior to total <em>FGFR2</em> expression levels. Longitudinal analysis of 33 paired pre- and post-treatment samples revealed treatment-induced increases in <em>FGFR2-IIIc</em> proportion (<em>P</em> = 0.0085), suggesting adaptive isoform switching. Notably, all tumors with elevated <em>FGFR2</em> expression exclusively belonged to the low-IIIc group, indicating that current FGFR2-targeted therapies primarily benefit patients with FGFR2-IIIb-dominant expression profiles. High-proportion <em>FGFR2-IIIc</em> was significantly associated with epithelial-to-mesenchymal transition and myogenesis pathway activation. Differential splicing analysis identified coordinated alternative splicing events in <em>ESRP1</em>-regulated targets, suggesting potential broader splicing dysregulation and providing mechanistic insights into the aggressive phenotype.</div></div><div><h3>Conclusions</h3><div><em>FGFR2-IIIc</em> proportion represents a clinically relevant prognostic biomarker in advanced GC/GEJCs. Treatment-induced isoform switching toward FGFR2-IIIc suggests a novel resistance mechanism requiring targeted therapeutic approaches. These findings underscore the importance of developing isoform-specific therapeutic strategies and implementing FGFR2-IIIc assessment in precision oncology approaches for GC/GEJCs.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105851"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145413706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive assessment of the existing landscape of personalized cancer medicine in the European Union, on behalf of the PCM4EU consortium","authors":"S.F. Haj Mohammad ,&nbsp;H. van der Pol ,&nbsp;E. Vrdoljak ,&nbsp;U. Lassen ,&nbsp;K. Ojamaa ,&nbsp;K. Jalkanen ,&nbsp;L. Verlingue ,&nbsp;A. Stenzinger ,&nbsp;A. Patócs ,&nbsp;G. Curigliano ,&nbsp;E. Baltruškevičienė ,&nbsp;Å. Helland ,&nbsp;H.G. Russnes ,&nbsp;I. Ługowska ,&nbsp;B. Mainoli ,&nbsp;A. Edsjö ,&nbsp;E. Lonardi ,&nbsp;K. Taskén ,&nbsp;H. Gelderblom","doi":"10.1016/j.esmoop.2025.105872","DOIUrl":"10.1016/j.esmoop.2025.105872","url":null,"abstract":"<div><h3>Background</h3><div>In the growing field of personalized cancer medicine (PCM), successful implementation requires access to advanced molecular diagnostics and treatments. The Personalized Cancer Medicine for all EU Citizens (PCM4EU) consortium was established to facilitate broad implementation of PCM across Europe. This study aimed to assess the current status of PCM from the perspectives of health care professionals and patients.</div></div><div><h3>Materials and methods</h3><div>Three distinct questionnaires were developed for medical oncologists, pathologists, and patients, focusing on molecular diagnostics use in countries participating in the PCM4EU consortium. Adult patients with locally advanced or metastatic cancer who underwent molecular diagnostics were eligible to complete the patient questionnaire.</div></div><div><h3>Results</h3><div>Between July 2024 and February 2025, 14 out of 15 countries completed the medical oncologist and pathologist questionnaires. Equitable access to molecular diagnostics was reported by 4 out of 14 countries, with limited access to treatments, clinical trials, or reimbursement issues identified as common barriers. Tumor-specific biomarkers matching approved targeted therapies were more often tested than tumor-agnostic biomarkers. Molecular tumor boards were established in 13 out of 14 countries. There was limited availability of complex biomarker testing techniques in several countries, and laboratories sometimes lacked accreditation by the International Organization for Standardization. A total of 288 patients from 16 countries completed the patient questionnaire. More comprehensible information regarding molecular diagnostics and better pre- and post-test genetic counseling were the main improvements reported by patients.</div></div><div><h3>Conclusions</h3><div>By use of extensive questionnaires, we assessed the implementation of PCM in Europe and identified persistent inequalities, ranging from disparities in available biomarker testing techniques to their reimbursement, and shortcomings in communication to patients. By facilitating access to similar treatments across countries with the establishment of a Drug Rediscovery Protocol-like clinical trials network, and accelerating data generation by sharing data, patients in Europe are one step closer to equitable access to precision oncology.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105872"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic profiling in hepatocellular carcinoma: a real-world retrospective analysis","authors":"F. Salani ,&nbsp;F.R. Ponziani ,&nbsp;F. Piscaglia ,&nbsp;U. Malapelle ,&nbsp;B. Daniele ,&nbsp;C. Porta ,&nbsp;L. Pradelli ,&nbsp;E. De Fiore ,&nbsp;G. Masi ,&nbsp;L. Rimassa ,&nbsp;A. Casadei Gardini","doi":"10.1016/j.esmoop.2025.105879","DOIUrl":"10.1016/j.esmoop.2025.105879","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with limited molecular characterization due to reliance on radiological diagnosis. This study aims to characterize the genomic landscape of advanced HCC and assess the prognostic and predictive roles of genetic alterations (GAs).</div></div><div><h3>Patients and methods</h3><div>This study used a de-identified nationwide (USA-based) HCC clinico-genomic database to retrospectively analyze patients with advanced HCC who received systemic therapies and underwent comprehensive genomic profiling via tissue or liquid biopsy. GAs were identified using Foundation Medicine, Inc.’s next-generation sequencing tests. Time to progression (TTP) was assessed using Kaplan–Meier analysis and Cox proportional hazards models.</div></div><div><h3>Results</h3><div>In total, 370 patients were analyzed. The most frequent GAs in the tissue cohort (<em>n</em> = 291) involved <em>TERT</em> promoter (<em>TERT</em>p, 61.5%), <em>CTNNB1</em> (34.0%), and <em>TP53</em> (33.0%). Key affected pathways were cell cycle and apoptosis (56%), DNA damage and control (43%), WNT (40.9%), and p53 (38.1%). Viral etiology was significantly associated with alterations in <em>TERT</em>p, <em>CTNNB1</em>, and the WNT pathway, while non-viral HCC was associated with alterations in the RTK/RAS pathway. TTP analysis revealed a trend toward improved outcomes with atezolizumab + bevacizumab (A + B) compared with tyrosine kinase inhibitors. <em>TP53,</em> p.V157F, and p.R249S mutations were associated with significantly shorter TTP. <em>MYC</em> seemed to be a negative predictor for A + B versus tyrosine kinase inhibitors, but statistical significance was not reached.</div></div><div><h3>Conclusions</h3><div>This study highlights the genomic landscape of advanced HCC, identifying cell cycle and apoptosis, DNA damage and control, WNT, and p53 as the key affected pathways. Further research is warranted to confirm such findings.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105879"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"All roads lead to ROME: convergence of evidence in precision oncology","authors":"V. Subbiah","doi":"10.1016/j.esmoop.2025.105902","DOIUrl":"10.1016/j.esmoop.2025.105902","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105902"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Access to anticancer and orphan medicines through compassionate use programs and named patient basis in seven European countries","authors":"N. Rosenberg ,&nbsp;H.C. Post ,&nbsp;T. Schutte ,&nbsp;S.J. de Visser ,&nbsp;I. Bartelink ,&nbsp;A.M.G. Pasmooij ,&nbsp;H.W.M. van Laarhoven ,&nbsp;C.E.M. Hollak","doi":"10.1016/j.esmoop.2025.105855","DOIUrl":"10.1016/j.esmoop.2025.105855","url":null,"abstract":"<div><h3>Background</h3><div>In the European Union (EU), anticancer and orphan medicines are often granted marketing authorization based on surrogate endpoints and limited clinical trial data. Driven by unmet medical needs and the urgency of providing access beyond clinical trials, there is growing interest in early access, such as compassionate use programs (CUPs) and named patient basis (NPB). Additionally, limited clinical evidence can hinder health technology assessments and, when combined with high costs, delay reimbursement negotiations and patient access. Hence, it is crucial to explore CUPs and NPBs including pricing and reimbursement aspects.</div></div><div><h3>Design</h3><div>This study includes a policy analysis to evaluate CUPs and NPBs in seven high-income European countries (Belgium, France, Germany, Netherlands, Norway, Switzerland, and the UK). We collected data on regulatory characteristics, including reimbursement aspects, from national health authority resources and direct consultations. In an in-depth examination, we assessed CUPs of anticancer and orphan medicines authorized in 2021 and 2022, focusing on availability, duration, and geographic distribution.</div></div><div><h3>Results</h3><div>Our analysis reveals variability in national regulations, with inconsistent reimbursement options for CUPs and NPBs. For NPBs, reimbursement was often unregulated. The in-depth examination of CUPs revealed disparities in availability and duration before and after EU marketing authorization. We identified 36 CUPs, with 3-9 CUPs per country. Each CUP was available in up to four countries.</div></div><div><h3>Conclusion</h3><div>We recommend minimizing disparities between CUPs and NPBs across Europe to ensure equitable access for patients with high unmet medical needs. Reducing these differences is essential to protect patients from feeling compelled to travel abroad or bear the financial burden of obtaining medicines that are not authorized in their home country.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105855"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zanidatamab in combination with docetaxel in first-line HER2-positive breast cancer: results from an open-label, multicenter, phase Ib/II study","authors":"X. Wang ,&nbsp;K.S. Lee ,&nbsp;X. Zeng ,&nbsp;T. Sun ,&nbsp;Y.-H. Im ,&nbsp;H. Li ,&nbsp;K. Wang ,&nbsp;P. Zhou ,&nbsp;V. Li ,&nbsp;S. Chen ,&nbsp;Z. Jiang","doi":"10.1016/j.esmoop.2025.105852","DOIUrl":"10.1016/j.esmoop.2025.105852","url":null,"abstract":"<div><h3>Background</h3><div>Most patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop resistance or relapse. Zanidatamab is a novel, humanized, dual-HER2-targeted bispecific antibody with antitumor activity and a manageable safety profile as monotherapy in HER2-positive cancers. This trial evaluated the efficacy and safety of zanidatamab with docetaxel as first-line treatment in HER2-positive breast cancer.</div></div><div><h3>Methods</h3><div>Cohort 1 of this open-label, multicenter, phase Ib/II trial enrolled adult patients from China or South Korea with histologically or cytologically confirmed unresectable, locally advanced, recurrent or metastatic HER2-positive breast cancer. Patients received intravenous zanidatamab 30 mg/kg with docetaxel 75 mg/m² or a flat dose of zanidatamab 1800 mg with docetaxel 75 mg/m² once every 3 weeks. Primary objectives were to evaluate the preliminary antitumor activity, safety, and tolerability of zanidatamab with docetaxel.</div></div><div><h3>Results</h3><div>At data cut-off (7 December 2023), 38 patients were enrolled in cohort 1; median study follow-up was 24.8 months. The confirmed objective response rate was 90.9%, disease control rate was 97.0%, and median duration of response was 23.5 months. Median time to response was 5.9 weeks. Median progression-free and overall survival were 22.1 months and 36.9 months, respectively. All patients experienced one or more treatment-emergent adverse events (TEAE), and 71.1% experienced grade ≥3 TEAEs. All patients had one or more treatment-related AE (TRAE), and 97.4% experienced zanidatamab-related TRAEs. Serious TEAEs were reported for 31.6% of patients: 18.4% had serious TRAEs, all of which were zanidatamab related. One death due to respiratory failure was recorded but was assessed as not related to study treatment. TEAEs and TRAEs leading to treatment discontinuation were recorded for 10.5% and 7.9% of patients, respectively.</div></div><div><h3>Conclusion</h3><div>Zanidatamab demonstrated efficacy and a manageable and tolerable safety profile with docetaxel as first-line treatment in patients with HER2-positive breast cancer. These data support the further development of zanidatamab in this patient population.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 11","pages":"Article 105852"},"PeriodicalIF":8.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}