ESMO Open最新文献

{"title":"Corrigendum to “An open-label, phase IB/II study of abemaciclib with paclitaxel for tumors with CDK4/6 pathway genomic alterations”","authors":"K.H. Kim , C. Park , S.-H. Beom , M.H. Kim , C.G. Kim , H.R. Kim , M. Jung , S.J. Shin , S.Y. Rha , H.S. Kim","doi":"10.1016/j.esmoop.2025.104542","DOIUrl":"10.1016/j.esmoop.2025.104542","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 5","pages":"Article 104542"},"PeriodicalIF":7.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815948","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":"Afatinib in patients with solid tumors with neuregulin 1 (NRG1) fusions: a case series from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study","authors":"J. Rodon ,&nbsp;M. Rothe ,&nbsp;P.K. Mangat ,&nbsp;E. Garrett-Mayer ,&nbsp;T.L. Cannon ,&nbsp;E. Hobbs ,&nbsp;G.P. Kalemkerian ,&nbsp;D.C. Hinshaw ,&nbsp;A. Gregory ,&nbsp;G.N. Grantham ,&nbsp;S. Halabi ,&nbsp;R.L. Schilsky","doi":"10.1016/j.esmoop.2025.104545","DOIUrl":"10.1016/j.esmoop.2025.104545","url":null,"abstract":"<div><h3>Background</h3><div>TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Results of four patients with various tumors with <em>NRG1</em> fusions treated with afatinib are reported.</div></div><div><h3>Patients and methods</h3><div>Eligible patients had advanced cancer, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with <em>NRG1</em> fusions, and no standard treatment options. The primary endpoint was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks’ duration (SD16+). Secondary endpoints included OR, duration of response, duration of SD, and safety.</div></div><div><h3>Results</h3><div>Four patients were enrolled from February 2020 to July 2021; all had solid tumors [colorectal cancer (<em>n</em> = 2), non-small-cell lung cancer (<em>n</em> = 1), and pancreatic adenocarcinoma (<em>n</em> = 1)] with an <em>NRG1</em> fusion. All patients were evaluable for efficacy. One partial response and two SD16+ were observed. One patient was still alive as of October 2024 with SD of 134 weeks’ duration. No patients had a drug-related grade 3-5 adverse event (AE) or serious AE.</div></div><div><h3>Conclusion</h3><div>Though the sample size was small, afatinib demonstrated promising activity in patients with advanced solid tumors with <em>NRG1</em> fusions, including durable DC warranting additional study.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 5","pages":"Article 104545"},"PeriodicalIF":7.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815947","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":"Claudin 18.2: a promising actionable target in biliary tract cancers","authors":"V. Angerilli ,&nbsp;D. Sacchi ,&nbsp;M. Rizzato ,&nbsp;J. Gasparello ,&nbsp;C. Ceccon ,&nbsp;M. Sabbadin ,&nbsp;M. Niero ,&nbsp;F. Bergamo ,&nbsp;U. Cillo ,&nbsp;C. Franzina ,&nbsp;C. Luchini ,&nbsp;A.P. Dei Tos ,&nbsp;S. Lonardi ,&nbsp;M. Fassan","doi":"10.1016/j.esmoop.2025.105049","DOIUrl":"10.1016/j.esmoop.2025.105049","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Anti-claudin 18.2 (anti-CLDN18.2) therapy has been approved for patients with CLDN18-positive gastric and gastroesophageal junction adenocarcinomas. The current study aims at evaluating the expression of CLDN18 in a large cohort of pathologically characterized biliary tract cancers (BTCs).</div></div><div><h3>Materials and methods</h3><div>A series of 237 BTCs were collected and reviewed under the BITCOIN protocol. All samples were assessed for CLDN18 status using immunohistochemistry (clone 43-14A). Tumor positivity for CLDN18 was determined if ≥75% of tumor cells exhibited moderate-to-strong membranous staining.</div></div><div><h3>Results</h3><div>CLDN18 expression was found in 29.5% of BTCs (70/237), with the highest rates in gallbladder carcinoma (GBC; 62.5%; 20/32) and extrahepatic cholangiocarcinoma (eCCA; 53.4%; 31/58), compared with intrahepatic cholangiocarcinoma (iCCA; 12.9%; 19/147) (<em>P</em> &lt; 0.0001). CLDN18 positivity was detected in 5.5% of cases (13/237), most common in GBC (15.6%; 5/32), followed by eCCAs (8.6%; 5/58) and iCCAs (2.0%; 3/147) (<em>P</em> = 0.0045). Most CLDN18-positive samples (10/13) exhibited a heterogenous staining pattern. In iCCAs, large duct subtypes had higher CLDN18 expression [33.3% (10/30) versus 7.7% (9/117), <em>P</em> = 0.0002] and positivity [6.7% (2/30) versus 0.9% (1/117), <em>P</em> = 0.106] than small duct iCCAs. No significant differences were observed across GBC and eCCA histotypes, and CLDN18 was not associated with <em>IDH1</em> or <em>FGFR2</em> status in iCCAs.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that CLDN18 expression is present in a subset of BTCs, with significantly higher positivity rates in GBCs and eCCAs compared with iCCAs. In iCCAs, CLDN18 expression was more frequent in the large duct subtype but was not associated with <em>IDH1</em> or <em>FGFR2</em> status. These findings suggest that CLDN18 could be a potential therapeutic target in BTCs, warranting further prospective studies to evaluate its clinical significance and impact on patient outcomes.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 5","pages":"Article 105049"},"PeriodicalIF":7.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815973","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":"Molecular targeted maintenance therapy versus standard of care in advanced biliary cancer: an international, randomised, controlled, open-label, phase III umbrella trial (SAFIR-ABC10—Precision Medicine)","authors":"D. Malka ,&nbsp;I. Borbath ,&nbsp;A. Lopes ,&nbsp;D. Couch ,&nbsp;M. Jimenez ,&nbsp;T. Vandamme ,&nbsp;J.W. Valle ,&nbsp;J. Wason ,&nbsp;E. Ambrose ,&nbsp;L. Dewever ,&nbsp;I. De Bruyne ,&nbsp;J. Edeline ,&nbsp;J. Bridgewater","doi":"10.1016/j.esmoop.2025.104540","DOIUrl":"10.1016/j.esmoop.2025.104540","url":null,"abstract":"<div><h3>Background</h3><div>Advanced biliary tract cancers (ABCs) are a heterogeneous group of rare malignancies of the bile ducts and gall-bladder with a poor prognosis and limited treatment options. Cisplatin–gemcitabine (CISGEM) chemotherapy plus immunotherapy (durvalumab or pembrolizumab) is the current first-line standard of care (1L-SoC). ABCs frequently harbour actionable molecular alterations that suggest a high potential for benefit from molecular targeted therapies (MTTs). However, the assessment of potential first-line MTT treatments is hindered by the scarcity of ABCs harbouring a specific alteration and the time required to carry out tumour molecular profiling.</div></div><div><h3>Materials and methods</h3><div>We detail here the design of SAFIR-ABC10, an international, randomised, phase III umbrella trial comparing the efficacy of sequential matched targeted therapy after four cycles (12 weeks) of 1L-SoC versus continued 1L-SoC in patients with ABC and an actionable molecular alteration [European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) tier I or II]. The primary study endpoint is progression-free survival. Besides initial tumour and circulating DNA next-generation sequencing analysis, sequential blood and tumour sampling will be carried out to identify biomarkers of prognosis, response and acquired resistance.</div></div><div><h3>Perspectives</h3><div>SAFIR-ABC10 is, to our knowledge, the first randomised, umbrella trial assessing the concept of precision medicine in ABC, the ideal setting for addressing this question with a high rate of targetable alterations.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 5","pages":"Article 104540"},"PeriodicalIF":7.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807777","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":"Final results from the phase Ia/Ib study of the novel bromodomain and extra-terminal domain inhibitor, BI 894999, in patients with advanced solid tumors or diffuse large B-cell lymphoma","authors":"U.M. Lauer ,&nbsp;A. Awada ,&nbsp;S. Postel-Vinay ,&nbsp;G.I. Shapiro ,&nbsp;C. Thieblemont ,&nbsp;S.A. Piha-Paul ,&nbsp;P.K. Paik ,&nbsp;D.R. Shepard ,&nbsp;L.I. Docampo ,&nbsp;R. Galot ,&nbsp;S. Rottey ,&nbsp;B. Sadrolhefazi ,&nbsp;K. Marzin ,&nbsp;H. Musa ,&nbsp;P. Schöffski","doi":"10.1016/j.esmoop.2025.104499","DOIUrl":"10.1016/j.esmoop.2025.104499","url":null,"abstract":"<div><h3>Background</h3><div>Bromodomain and extraterminal domain (BET) inhibitors have demonstrated efficacy in solid and hematological malignancies. BI 894999, a novel, orally administered BET inhibitor, has demonstrated preclinical efficacy.</div></div><div><h3>Methods</h3><div>This was an open-label, dose-finding study evaluating BI 894999 for diffuse large B-cell lymphoma (DLBCL; phase Ia extension) and solid tumors [colorectal cancer (CRC), nuclear protein in testis (NUT) carcinoma, metastatic castration-resistant prostate cancer (mCRPC) and small-cell lung cancer (SCLC); phase Ib cohort]. The primary endpoint was dose-limiting toxicities (DLTs) during the maximum tolerated dose (MTD) period (phase Ia) and treatment period (phase Ib).</div></div><div><h3>Results</h3><div>Eighteen patients with DLBCL were enrolled in the phase Ia extension and 79 with solid tumors in phase Ib cohorts (SCLC, <em>n</em> = 12; CRC, <em>n</em> = 14; mCRPC, <em>n</em> = 11; NUT carcinoma, <em>n</em> = 42). Four patients had DLTs in phase Ia and 17 in phase Ib; the most frequent was grade 4 thrombocytopenia. The MTD for DLBCL was 1.5 mg (days 1-14/21). One patient (5.6%) with DLBCL achieved a partial response (PR) and three (16.7%) had stable disease. Of 42 patients with NUT carcinoma, 3 patients (7.1%) had responses (complete response, <em>n</em> = 1; confirmed PR, <em>n</em> = 1; unconfirmed PR, <em>n</em> = 1). Responses in other solid tumor types (<em>n</em> = 37) included one patient (2.7%) with mCRPC who had a confirmed PR.</div></div><div><h3>Conclusions</h3><div>The safety profile of BI 894999 was consistent with those of other BET inhibitors. Due to minimal efficacy results, further evaluation of BI 894999 as monotherapy is not planned.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 5","pages":"Article 104499"},"PeriodicalIF":7.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective multicentric survival analysis of patients receiving TPEx regimen as first-line treatment of recurrent and/or metastatic head and neck squamous cell carcinoma","authors":"L. Libert ,&nbsp;C. Abdeddaim ,&nbsp;K. Saleh ,&nbsp;C. Even ,&nbsp;S. Duplomb ,&nbsp;J. Dubreuil ,&nbsp;A. Rambeau ,&nbsp;E. Guiard ,&nbsp;Y. Pointreau ,&nbsp;N. Olympios-Gerotzortzos ,&nbsp;C. Moldovan ,&nbsp;E. Lévêque ,&nbsp;F. Clatot","doi":"10.1016/j.esmoop.2025.104544","DOIUrl":"10.1016/j.esmoop.2025.104544","url":null,"abstract":"<div><h3>Background</h3><div>TPEx regimen (docetaxel, platinum, cetuximab) is a first-line treatment option for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) if combined positive score &lt;1, or in case of high tumor burden. We sought to evaluate the survival rates of patients receiving TPEx in real life as first-line treatment of R/M HNSCC, particularly since the advent of immunotherapy (IO) as second-line therapy.</div></div><div><h3>Methods</h3><div>This multicentric retrospective study included patients treated by a first cycle of TPEx between 2018 and 2023, with a performance status of 0 or 1. The primary endpoint was overall survival (OS). Secondary end-points were progression free survival (PFS1), rate of patients exposed to IO after TPEx, PFS of patients on second line treatment (PFS2).</div></div><div><h3>Results</h3><div>A total of 204 patients were included, mainly men (86%), previously treated for a localized HNSCC (78%). Some 32% of patients had a clinically threatening disease. Combined positive score was available for 88 patients (43%). Patients were treated with a median of four cycles of TPEx, followed by cetuximab maintenance for 154 patients. After a median follow-up of 35.8 months, median OS was 17.9 months [95% confidence interval (CI) 15.7-19.6 months], median PFS1 was 6.0 months (95% CI 5.7-6.9 months) and median PFS2 was 2.5 months (95% CI 2.0-2.8 months). Among the 182 patients who progressed under TPEx, 148 patients were exposed to IO (81.3%) in subsequent lines.</div></div><div><h3>Conclusion</h3><div>Median OS of 17.9 months under TPEx as first-line treatment of R/M HNSCC compares favorably with historical data. IO exposure after progression on TPEx was the rule.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104544"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816995","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":"LUDICAS: sexual dysfunction in patients with lung cancer, a multicenter cross-sectional study☆","authors":"A.V. Ospina-Serrano ,&nbsp;A. Collazo-Lorduy ,&nbsp;E. Azkona-Uribelarrea ,&nbsp;P. Guillen-Sentís ,&nbsp;F. Aparisi ,&nbsp;R. López ,&nbsp;P. Cruz ,&nbsp;A. Valdivia ,&nbsp;P. Cordeiro ,&nbsp;A. Olivares-Hernández ,&nbsp;M. Blanco ,&nbsp;R. Casas-Cornejo ,&nbsp;E. Carcereny ,&nbsp;M. Dómine ,&nbsp;M. Antoñanzas ,&nbsp;A. Blasco-Cordellat ,&nbsp;D. Peralta ,&nbsp;M. Sereno ,&nbsp;A. Cardeña-Gutiérrez ,&nbsp;R. Romão ,&nbsp;M. Provencio-Pulla","doi":"10.1016/j.esmoop.2025.104539","DOIUrl":"10.1016/j.esmoop.2025.104539","url":null,"abstract":"<div><h3>Background</h3><div>Patients with lung cancer may suffer from sexual dysfunction (SD) related to oncological treatment. This is an under-recognized condition among clinicians. The aim of this study was to describe the prevalence of SD in a multicenter cohort of patients.</div></div><div><h3>Patients and methods</h3><div>This multicenter, cross-sectional, observational study was conducted between July 2023 and February 2024. Sexual function was assessed by patient-reported outcome (PRO) system using sex-specific questionnaire. Descriptive analysis and evaluation of differences between categorical variables were carried out. Associations between clinical characteristics and SD were assessed by logistic regression.</div></div><div><h3>Results</h3><div>Four hundred and forty-eight patients from 24 hospitals in Spain, Colombia, Argentina, and Portugal were included. Of these, 277 (61.83%) were male and 365 (81.48%) had metastatic disease. Two hundred and eighty-four patients (63.39%) reported the onset of SD following the initiation of oncological treatment. Males and females reported a high frequency of severe impairment of sexual response phases, which was twice as high in females (<em>P</em> <em>=</em> 0.001). Female sex was a factor for severe impairment of desire, arousal, and orgasm [odds ratio (OR) 3.72, 95% confidence interval (CI) 2.48-5.60, <em>P</em> <em>=</em> 0.001] and decreased sexual activity (OR 1.98, 95% CI:1.17-3.19, <em>P</em> = 0.01), in addition to age over 65 years (OR 3.86, 95% CI 1.01-15.25, <em>P</em> <em>=</em> 0.004) and high educational level (OR 0.29, 95% CI 0.09-0.94, <em>P</em> <em>=</em> 0.0040). Patients from Portugal and Latin America were more likely to report dissatisfaction with sexual activity (OR 3.75, 95% CI 1.06-13.22, <em>P</em> <em>=</em> 0.0039). Female sex (OR 3.53, 95% CI 1.88-6.6, <em>P</em> 0.001), smoking history (OR 1.77, 95% CI 1.01-4.01, <em>P</em> <em>=</em> 0.04), and obesity (OR 1.70 95% CI 1.01-3.16, <em>P</em> <em>=</em> 0.05) were associated with global sexual dissatisfaction.</div></div><div><h3>Conclusions</h3><div>Our patients with lung cancer had a high prevalence of SD after initiation of oncological treatment. There was remarkable sex disparity in the frequency and severity of this disorder as well as an important influence of sociocultural factors in the clinical presentation.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104539"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosis, clinicopathological characteristics, and treatment patterns of patients with ER-intermediate-positive breast cancer undergoing long-term follow-up","authors":"N. Matsumoto ,&nbsp;Y. Wanifuchi-Endo ,&nbsp;T. Fujita ,&nbsp;T. Asano ,&nbsp;M. Terada ,&nbsp;K. Nozawa ,&nbsp;M. Mori ,&nbsp;A. Isogai ,&nbsp;Y. Niwa ,&nbsp;H. Kato ,&nbsp;M. Komura ,&nbsp;T. Toyama","doi":"10.1016/j.esmoop.2025.104508","DOIUrl":"10.1016/j.esmoop.2025.104508","url":null,"abstract":"<div><h3>Background</h3><div>Estrogen receptor (ER) expression levels in breast cancer tissue predict the efficacy of endocrine therapy and the prognosis of breast cancer patients. Recently, it was reported that the prognosis of patients with ER-low-positive breast cancer was similar to that of ER-negative patients. This study aimed to investigate how ER expression levels impact the prognosis of patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer undergoing long-term follow-up.</div></div><div><h3>Patients and methods</h3><div>The correlation between ER expression levels and prognosis was retrospectively evaluated in a cohort of 3091 consecutive patients with HER2-negative early breast cancer who were treated at our institute between 1981 and 2022. The median follow-up period was 85.2 (range 0-480) months. The proportion of ER-expressing cells in breast cancer tissues was assessed by immunohistochemistry and used to classify patients into four categories: ER negative (&lt;1%), ER-low positive (1% ≤ ER &lt; 10%), ER-intermediate positive (10% ≤ ER &lt; 2/3), and ER-high positive (≥2/3).</div></div><div><h3>Results</h3><div>Patients with ER-intermediate-positive breast cancer had a prognosis similar to that of patients with ER-low-positive or ER-negative disease. By contrast, patients with ER-high-positive breast cancer had significantly longer disease-free survival (DFS) and overall survival (OS) times than the other groups. Multivariate analysis demonstrated that ER-intermediate positivity was an independent factor for poor prognosis for both DFS and OS in patients with HER2-negative early breast cancer. The distributions of tumor grades 1, 2, and 3 were nearly equal among the ER-intermediate-positive patients, whereas more than half of patients with ER-high-positive breast cancer had grade 1 tumors. By analyzing changes in prognosis over time, we found that the prognosis of patients with ER-high-positive breast cancer markedly improved over three decades, while that of patients with ER-intermediate-positive disease did not.</div></div><div><h3>Conclusions</h3><div>Patients with ER-intermediate-positive breast cancer differ from patients with ER-high-positive breast cancer, suggesting that the treatment of ER-positive breast cancer patients should be tailored based on ER expression levels.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104508"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefit from maintenance with PARP inhibitor in newly diagnosed ovarian cancer according to BRCA1/2 mutation type and site: a multicenter real-world study","authors":"C. Marchetti ,&nbsp;A. Fagotti ,&nbsp;R. Fruscio ,&nbsp;C. Cassani ,&nbsp;L. Incorvaia ,&nbsp;M.T. Perri ,&nbsp;C.M. Sassu ,&nbsp;C.A. Camnasio ,&nbsp;E. Giudice ,&nbsp;A. Minucci ,&nbsp;M. Seca ,&nbsp;E. Arbustini ,&nbsp;L. Vertechy ,&nbsp;M. De Bonis ,&nbsp;S.M. Boccia ,&nbsp;D. Giannarelli ,&nbsp;V. Salutari ,&nbsp;M. Distefano ,&nbsp;M.G. Ferrandina ,&nbsp;C. Nero ,&nbsp;D. Lorusso","doi":"10.1016/j.esmoop.2025.104533","DOIUrl":"10.1016/j.esmoop.2025.104533","url":null,"abstract":"<div><h3>Background</h3><div>Knowledge about the association between the <em>BRCA1/2</em> mutation type and location and response to poly (ADP-ribose) polymerase inhibitors (PARPis) as single agent in ovarian cancer is limited. This study aimed to investigate the effectiveness of PARPi based on functional domains (FD) [RING, BRCT, DNA-binding (BD), RAD51-BD] and types (frameshift, missense, nonsense, splicing) of <em>BRCA1/2</em> gene mutations in ovarian cancer.</div></div><div><h3>Materials and methods</h3><div>This multicenter real-world study retrospectively enrolled <em>BRCA1/2</em>-mutated ovarian cancer patients receiving olaparib maintenance between January 2010 and December 2022. Data were compared with historical series of patients who did not receive olaparib and analyzed based on the FD involved in <em>BRCA1/2</em> mutations. Progression-free survival was calculated from the date of the last platinum-based treatment until recurrence or last follow-up.</div></div><div><h3>Results</h3><div>After a median follow-up of 46 months (range 32-60 months), 140 patients who underwent olaparib maintenance were compared with 128 who did not. PARPi showed efficacy in the overall population. The no-exon 11 patients benefitted more from olaparib than exon 11 patients [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.25-0.93]. In the <em>BRCA1</em> group, patients with mutations in RING and BRCT domains had significant benefits from PARPi (HR 0.08, 95% CI 0.01-0.75; HR 0.10, 95% CI 0.02-0.38, respectively). Among <em>BRCA2</em>-mutated patients, RAD51-BD mutations were associated with higher response to olaparib (HR 0.23, 95% CI 0.10-0.52). According to the mutation type, the major effect of PARPi was in the missense group (HR 0.04, 95% CI 0.01-0.31). No patients with p.(Ala1708Glu) in the BRCT domain (<em>BRCA1</em>) receiving PARPi experienced recurring disease in the study period.</div></div><div><h3>Conclusions</h3><div><em>BRCA1/2</em>-mutated patients benefit from olaparib, but with variations according to the mutation type and FDs. <em>BRCA1</em>-mutated patients in the RING or BRCT and <em>BRCA2</em>-mutated in the RAD51-BD have the greatest benefit. Patients with missense mutations, especially those with p.(Ala1708Glu), have the most significant advantage from maintenance with PARPi.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104533"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitors use in lung transplant recipients: a case series and systematic review of literature","authors":"N. Mahmoud ,&nbsp;G. Pamart ,&nbsp;C. Nardin ,&nbsp;A. Schuller ,&nbsp;S. Hirschi ,&nbsp;T. Dégot ,&nbsp;P.-E. Falcoz ,&nbsp;A. Olland ,&nbsp;C.-A. Tacquard ,&nbsp;R. Kessler ,&nbsp;B. Coiffard ,&nbsp;B. Renaud-Picard","doi":"10.1016/j.esmoop.2025.104537","DOIUrl":"10.1016/j.esmoop.2025.104537","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) are an innovative treatment that has improved long-term survival in several neoplastic diseases over the past decade. Solid organ transplant (SOT) recipients, particularly lung transplant (LTx) recipients, have been largely excluded from clinical trials evaluating the safety and efficiency of ICIs, because of the perceived high risk of allograft rejection. In this study, we sought to evaluate the use of ICIs for all neoplastic diseases in LTx patients in all French LTx centers and two Belgian centers. We found only a limited number of cases in which ICIs were suggested to two patients due to a lack of alternative treatments. In the first case, acute respiratory failure and death occurred, whereas in the second case, ICI treatment was well tolerated and resulted in a partial response. In addition, we presented the case of a third LTx patient in whom the use of ICIs was considered but not used due to the patient’s comorbidities. This last case highlights the difficulty of discussing the risk–benefit balance, which ultimately did not favor ICI treatment of this patient. Further multicenter randomized controlled trials are necessary to investigate the safety and efficacy of ICIs in LTx recipients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104537"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}