ESMO Open最新文献

{"title":"Longer survival with precision medicine in late-stage cancer patients☆","authors":"C.K. Mapendano ,&nbsp;A.K. Nøhr ,&nbsp;M. Sønderkær ,&nbsp;A. Pagh ,&nbsp;A. Carus ,&nbsp;T. Lörincz ,&nbsp;C.A. Haslund ,&nbsp;L.Ø. Poulsen ,&nbsp;A. Ernst ,&nbsp;J.S. Bødker ,&nbsp;S.C. Dahl ,&nbsp;L. Sunde ,&nbsp;A.H. Brügmann ,&nbsp;C. Vesteghem ,&nbsp;I.S. Pedersen ,&nbsp;M. Ladekarl","doi":"10.1016/j.esmoop.2024.104089","DOIUrl":"10.1016/j.esmoop.2024.104089","url":null,"abstract":"<div><h3>Background</h3><div>In a per-protocol analysis of molecularly profiled patients with treatment-refractory, end-stage cancer discussed at the National Molecular Tumor Board (NMTB), we aimed to assess the overall survival (OS) outcome of targeted treatment compared with no targeted treatment.</div></div><div><h3>Materials and methods</h3><div>Patients were prospectively included at a single oncological center. Whole exome and RNA sequencing (tumor-normal) were carried out, and cases were presented at the NMTB for discussion of targeted treatment. Treatment was available through a basket trial, by compassionate use or in early clinical trials.</div></div><div><h3>Results</h3><div>One hundred and ninety-six patients were included from 2020 to 2023. In all but three patients a driver variant was disclosed, while 42% had simultaneous affection of more than three oncogenic pathways. In 42% of patients a druggable target was identified but two-thirds did not receive the suggested treatment. The fraction of patients initiating treatment yearly rose from 8% to 22%. For patients treated (<em>N</em> = 30), the clinical benefit rate was 44% and median time on treatment was 3.5 months. Druggable targets were enriched in lung cancers, while patients receiving or not receiving targeted treatment had similar clinical characteristics. The median OS was longer for patients receiving targeted treatment (15 months), but similar for patients with no druggable target and suggested targeted treatment not initiated (5 and 6 months, respectively) (<em>P</em> = 0.004). In multivariate analysis, targeted treatment (hazard ratio 0.43, confidence interval 0.25-0.72), few metastatic sites, and adenocarcinoma histology were predictive of improved OS while alterations of the RTK/RAS pathway were prognostically unfavorable.</div></div><div><h3>Conclusions</h3><div>Tissue-agnostic targeted treatment based on molecular tumor profiling is possible in an increasing fraction of end-stage cancer patients. In those who receive targeted treatment, results strongly suggest a significant survival benefit.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104089"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926921","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":"Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients","authors":"A. Gravina ,&nbsp;P. Gargiulo ,&nbsp;M. De Laurentiis ,&nbsp;L. Arenare ,&nbsp;S. De Placido ,&nbsp;M. Orditura ,&nbsp;S. Cinieri ,&nbsp;F. Riccardi ,&nbsp;A.S. Ribecco ,&nbsp;C. Putzu ,&nbsp;L. Del Mastro ,&nbsp;E. Rossi ,&nbsp;F. Ciardiello ,&nbsp;F. Di Rella ,&nbsp;F. Nuzzo ,&nbsp;C. Pacilio ,&nbsp;R. Caputo ,&nbsp;D. Cianniello ,&nbsp;V. Forestieri ,&nbsp;M. Giuliano ,&nbsp;F. Perrone","doi":"10.1016/j.esmoop.2024.104085","DOIUrl":"10.1016/j.esmoop.2024.104085","url":null,"abstract":"<div><h3>Background</h3><div>The Hormonal Bone Effects (HOBOE) study tested whether adjuvant triptorelin plus either letrozole (L) or zoledronic acid (Z) plus L (ZL) was more effective than tamoxifen (T) in premenopausal patients with hormone receptor-positive (HR+) early breast cancer (BC). Here we report the long-term follow-up analysis.</div></div><div><h3>Patients and methods</h3><div>HOBOE (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> number NCT00412022) is an open-label, three-arm, randomised, phase III trial that involved 16 centres in Italy. One thousand and sixty-five premenopausal patients with HR+ early BC receiving triptorelin were randomly assigned (1 : 1 : 1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis.</div></div><div><h3>Results</h3><div>As of 24 October 2024 at a median follow-up of 9.2 years, 199 DFS events and 79 deaths were reported. Both ZL and L improved DFS over T, with a hazard ratio (HR) of 0.58 [95% confidence interval (CI) 0.41-0.82; <em>P</em> = 0.002] for ZL versus T and 0.69 (95% CI 0.49-0.97, <em>P</em> = 0.030) for L versus T. No statistically significant difference in OS was reported (global log-rank <em>P</em> = 0.103). The previously reported statistically significant interaction with human epidermal growth factor receptor 2 (HER2) status was confirmed for ZL versus T comparison (<em>P</em> = 0.007).</div></div><div><h3>Conclusion</h3><div>In this updated analysis, L plus triptorelin, with or without Z, demonstrated a statistically significant DFS improvement over T plus triptorelin for the adjuvant treatment of early BC in premenopausal patients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"Article 104085"},"PeriodicalIF":7.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926924","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":"Beyond the sarcoma center: establishing the Sarcoma HASM network—a Hub and Spoke Model network for global integrated and precision care","authors":"B. Fuchs ,&nbsp;A. Gronchi","doi":"10.1016/j.esmoop.2024.103734","DOIUrl":"10.1016/j.esmoop.2024.103734","url":null,"abstract":"<div><div>The landscape of sarcoma treatment has evolved significantly, transitioning from amputations to limb-sparing surgeries, underpinned by advancements in multidisciplinary strategies. The establishment of specialized sarcoma centers has been pivotal, though challenges in accessibility and expertise persist. This manuscript proposes the Sarcoma Hub and Spoke Model (HASM) network to address these issues, enhancing coordination and expanding access to specialized care. The HASM network centralizes complex case management at hubs while peripheral spokes manage routine diagnostics and treatments, optimizing resource use and ensuring patient-centered care. Integration with digital interoperable platforms facilitates real-time/real-world data exchange, supports multidisciplinary team meetings, and enables advanced predictive analytics such as Sarcoma Digital Twins and causal machine learning for personalized treatment. The Sarcoma Care Data Warehouse further enhances this model by aggregating comprehensive patient data, supporting quality assessment and continuous improvement. This innovative approach aims to set a new standard for sarcoma care, leveraging technology and collaborative expertise to improve outcomes globally.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103734"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791337","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":"Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial","authors":"T.K. Choueiri ,&nbsp;T.M. Kuzel ,&nbsp;S.S. Tykodi ,&nbsp;E. Verzoni ,&nbsp;H. Kluger ,&nbsp;S. Nair ,&nbsp;R. Perets ,&nbsp;S. George ,&nbsp;H. Gurney ,&nbsp;R.K. Pachynski ,&nbsp;E. Folefac ,&nbsp;V. Castonguay ,&nbsp;C.-H. Lee ,&nbsp;U. Vaishampayan ,&nbsp;W.H. Miller Jr. ,&nbsp;P. Bhagavatheeswaran ,&nbsp;Y. Wang ,&nbsp;S. Gupta ,&nbsp;H. DeSilva ,&nbsp;C.-W. Lee ,&nbsp;R.J. Motzer","doi":"10.1016/j.esmoop.2024.104073","DOIUrl":"10.1016/j.esmoop.2024.104073","url":null,"abstract":"<div><h3>Background</h3><div>The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology study in patients with aRCC (FRACTION-RCC) was designed to assess new immuno-oncology (IO) combinations in patients with advanced renal cell carcinoma (aRCC). We present results in IO-naive patients treated with nivolumab (NIVO) + relatlimab (RELA) or NIVO + ipilimumab (IPI) in track 1.</div></div><div><h3>Methods</h3><div>The open-label, randomised, phase II FRACTION-RCC trial enrolled patients with aRCC from 32 hospitals and cancer centres across six countries. Patients were enrolled in track 1 (IO-naive) or track 2 (IO-experienced). IO-naive patients were stratified by previous tyrosine kinase inhibitor therapy and randomised to NIVO (240 mg) + RELA (80 mg) intravenously once every 2 weeks or NIVO (3 mg/kg) + IPI (1 mg/kg) intravenously once every 3 weeks for four doses, followed by NIVO (480 mg) once every 4 weeks, each up to ∼2 years. The primary endpoints were objective response by investigator (RECIST version 1.1), duration of response (DOR), and progression-free survival (PFS) rate at 24 weeks. Safety was a secondary endpoint; biomarker analyses were exploratory.</div></div><div><h3>Results</h3><div>FRACTION-RCC enrolled patients between 2 February 2017 and 23 January 2020. In track 1, 30 patients each were treated with NIVO + RELA or NIVO + IPI (clinical database lock, 1 November 2021). With NIVO + RELA [median follow-up, 48.6 months; interquartile range (IQR) 46.9-51.7 months], objective response was 30% [95% confidence interval (CI) 15% to 49%], with 33 weeks (95% CI 16-53 weeks) median DOR. The PFS rate at 24 weeks was 43% (95% CI 25% to 60%). With NIVO + IPI (median follow-up, 48.7 months; IQR 47.1-52.0 months), the objective response was 20% (95% CI 8% to 39%), with the median DOR not reached (95% CI 33 weeks-not estimable). The PFS rate at 24 weeks was 49% (95% CI 29% to 66%). Higher baseline lymphocyte activation gene 3 (LAG-3) and programmed death-ligand 1 (PD-L1) expression levels were detected among track 1 NIVO + RELA responders. Grade 3-4 treatment-related adverse events were reported in 4/30 (13%) patients treated with NIVO + RELA and 10/30 (33%) patients treated with NIVO + IPI. No deaths were attributed to study treatments.</div></div><div><h3>Conclusions</h3><div>Results showed antitumour activity and manageable safety with NIVO + RELA. Findings also support NIVO + IPI as an effective combination regimen in IO-naive patients with aRCC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 104073"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791345","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":"Uncertainties about the benefit-risk balance of oncology medicines assessed by the European Medicines Agency","authors":"A.C. Taams ,&nbsp;C.A. Herberts ,&nbsp;A.C.G. Egberts ,&nbsp;N. Zafiropoulos ,&nbsp;F. Pignatti ,&nbsp;L.T. Bloem","doi":"10.1016/j.esmoop.2024.103991","DOIUrl":"10.1016/j.esmoop.2024.103991","url":null,"abstract":"<div><h3>Background</h3><div>Drug regulators assess and describe uncertainties regarding treatment outcomes and the benefit-risk balance of newly authorised medicines. We aimed to evaluate the type and number of uncertainties described in the benefit-risk assessment for initial marketing authorisations of oncology medicines assessed by the European Medicines Agency (EMA). We also aimed to develop a systematic classification of uncertainties to contribute to improved communication about uncertainties.</div></div><div><h3>Materials and methods</h3><div>We included all medicines containing a new active substance assessed by the EMA and granted an initial marketing authorisation by the European Commission in 2011-2022 for an oncology indication. We extracted characteristics of these oncology medicines and uncertainties described under the benefit-risk balance section of European public assessment reports. Uncertainties were categorised and their frequencies stratified according to time of marketing authorisation, and medicine and regulatory characteristics.</div></div><div><h3>Results</h3><div>In total, 121 oncology medicines were included for which 800 (median 6, range 0-23) uncertainties were identified. Uncertainties were classified into five categories: safety (<em>n</em> = 404, 51%), efficacy (<em>n</em> = 322, 40%), pharmacology (<em>n</em> = 58, 7%), use in clinical practice (<em>n</em> = 10, 1%), and quality (<em>n</em> = 6, 1%). Among 27 subcategories, most uncertainties were related to specific adverse events (<em>n</em> = 156, 20%), effect size (<em>n</em> = 155, 20%), safety in subpopulations (<em>n</em> = 124, 16%), or efficacy in subpopulations (<em>n</em> = 88, 11%). The type of medicine (<em>P</em> = 0.012), type of marketing authorisation (<em>P</em> = 0.001), and year of marketing authorisation (<em>P</em> = 0.007) were associated with the number of uncertainties per medicine, with the highest number observed for cell and gene therapies [8 (3-23)], medicines granted conditional marketing authorisation [7 (3-23)], and medicines authorised in 2019-2022 [7 (2-23)].</div></div><div><h3>Conclusion</h3><div>At the time of initial marketing authorisation of oncology medicines, uncertainties about their benefit-risk balance most often concerned safety aspects, followed by efficacy. The number of uncertainties was highest for cell and gene therapies, conditionally authorised medicines, and medicines authorised in recent years.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103991"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806032","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":"Characteristics, treatment patterns and survival of patients with high-risk early hormone receptor-positive breast cancer in French real-world settings: an exploratory study of the CANTO cohort☆","authors":"F. Giugliano ,&nbsp;A. Bertaut ,&nbsp;J. Blanc ,&nbsp;A.-L. Martin ,&nbsp;C. Gaudin ,&nbsp;M. Fournier ,&nbsp;A. Kieffer ,&nbsp;B. Sauterey ,&nbsp;C. Levy ,&nbsp;M. Campone ,&nbsp;C. Tarpin ,&nbsp;F. Lerebours ,&nbsp;M.-A. Mouret-Reynier ,&nbsp;G. Curigliano ,&nbsp;F. André ,&nbsp;B. Pistilli ,&nbsp;E. Rassy","doi":"10.1016/j.esmoop.2024.103994","DOIUrl":"10.1016/j.esmoop.2024.103994","url":null,"abstract":"<div><h3>Background</h3><div>Patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (HR+ BC) with unfavorable features have an increased risk of relapse and are currently candidate for additional treatment strategies. We evaluated the real-world clinicopathological characteristics, treatment patterns and survival outcomes of these patients within the CANcer TOxicities study (CANTO, NCT01993498).</div></div><div><h3>Patients and methods</h3><div>This is a retrospective analysis of the prospective data collected within CANTO between 2012 and 2022. Patients with high-risk HR+ BC were defined either by the identification of at least four positive axillary lymph nodes (LNs) or one to three positive axillary LNs with a tumor size ≥5 cm or histologic grade 3 (cohort 1). The definition 1-3 positive LNs with Ki-67 ≥20% was also considered (cohort 2). The Kaplan–Meier method was used for survival analysis.</div></div><div><h3>Results</h3><div>Patients with high-risk HR+ BC represented 15.0%-19.6% of HR+ BC (cohort 1 and 2, respectively) in the CANTO cohort. Of the 1266 patients in cohort 1, 617 patients (49.0%) had ≥4 LNs, 327 (26.0%) had tumor ≥5 cm and 727 (57.6%) had grade III tumors. 79.9% had a favorable Charlson comorbidity score and 88.1% stage II/IIIA. Patients with ≥10 LNs accounted for 11.8%. (Neo)adjuvant chemotherapy was administered in 94.2%. Endocrine therapy was prescribed in 97.3%, mostly with aromatase inhibitors and discontinued in 34.3%, mainly for adverse events. Patients enrolled at least 6 years before data extraction had a 5-year invasive disease-free survival and 5-year distant relapse-free survival of 79.9% [95% confidence interval (CI) 77.2% to 82.4%] and 83.5% (95% CI 80.9% to 85.7%), respectively.</div></div><div><h3>Conclusions</h3><div>This real-world study confirms that patients with HR+ BC and unfavorable clinicopathological features are at risk of relapse early in their adjuvant treatment trajectory, despite (neo)adjuvant chemotherapy. It is imperative to implement innovative treatment approaches for high-risk patients, ideally adding them as early as possible to the adjuvant treatment.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103994"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746183","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":"The clinical dilemma of high-risk stage II colon cancer: are we truly prepared to withdraw oxaliplatin?","authors":"J. Taieb ,&nbsp;A. Gandini ,&nbsp;J.F. Seligmann ,&nbsp;C. Gallois","doi":"10.1016/j.esmoop.2024.104072","DOIUrl":"10.1016/j.esmoop.2024.104072","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 104072"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766872","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":"Prognostic value of radiologic and pathological response in colorectal cancer liver metastases upon systemic induction treatment: subgroup analysis of the CAIRO5 trial","authors":"M.J.G. Bond ,&nbsp;C. Mijnals ,&nbsp;K. Bolhuis ,&nbsp;M.J. van Amerongen ,&nbsp;M.R.W. Engelbrecht ,&nbsp;J.J. Hermans ,&nbsp;K.P. van Lienden ,&nbsp;A.M. May ,&nbsp;R.-J. Swijnenburg ,&nbsp;C.J.A. Punt","doi":"10.1016/j.esmoop.2024.104075","DOIUrl":"10.1016/j.esmoop.2024.104075","url":null,"abstract":"<div><h3>Background</h3><div>RECIST may not be optimal for assessing treatment response with current systemic regimens. We evaluated RECIST, morphologic, and pathologically documented response (pathological response) in patients with initially unresectable colorectal cancer liver-only metastases (CRLM).</div></div><div><h3>Patients and methods</h3><div>Four hundred and eighty-nine patients from the phase III CAIRO5 trial were included who were treated with FOLFOX/FOLFIRI/FOLFOXIRI and bevacizumab or panitumumab. The association of the different response tools with overall survival (OS) was evaluated for all patients, and with early recurrence (&lt;6 months) for patients after complete local treatment.</div></div><div><h3>Results</h3><div>In the overall population, suboptimal [hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.83-1.47] and optimal (HR 0.95, 95% CI 0.74-1.22) morphologic response were not associated with OS compared with no response. RECIST partial response (HR 0.61, 95% CI 0.49-0.76) and progressive disease (HR 5.77, 95% CI 3.97-8.39) were associated with OS compared with stable disease. In 242 patients who underwent local treatment, suboptimal (HR 1.22, 95% CI 0.76-1.96) and optimal (HR 1.28, 95% CI 0.89-1.86) morphologic response were not associated with OS compared with no response. RECIST partial response was not significantly associated with OS (HR 0.73, 95% CI 0.52-1.01), whereas progressive disease was (HR 19.74, 95% CI 5.75-67.78), compared with stable disease. While major pathological response (HR 0.66, 95% CI 0.44-0.99) was associated with OS, partial pathological response (HR 0.82, 95% CI 0.57-1.19) was not, compared with no pathological response. Pathological response, but not morphologic response and RECIST, was significantly associated with early recurrence (<em>P</em> &lt; 0.001) which occurred in 13/58 (22%) patients with major response, 29/61 (48%) patients with partial response, and 51/88 (58%) patients with no response.</div></div><div><h3>Conclusions</h3><div>Our results show that RECIST but not morphologic response was prognostic for OS. In patients eligible for local treatment, neither RECIST nor morphologic response were associated with early recurrence. Pathological response was associated with early recurrence but is only available post-operatively. Hence, novel preoperative parameters are warranted to predict early recurrence and prevent potentially futile liver surgery.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 104075"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817401","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":"Clinicopathological analysis of claudin 18.2 focusing on intratumoral heterogeneity and survival in patients with metastatic or unresectable gastric cancer","authors":"T.-Y. Kim ,&nbsp;Y. Kwak ,&nbsp;S.K. Nam ,&nbsp;D. Han ,&nbsp;D.-Y. Oh ,&nbsp;S.-A. Im ,&nbsp;H.S. Lee","doi":"10.1016/j.esmoop.2024.104000","DOIUrl":"10.1016/j.esmoop.2024.104000","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to investigate the prevalence of claudin 18.2 (CLDN18.2) positivity, with a particular focus on intratumoral heterogeneity, and its association with clinicopathological features in metastatic or unresectable gastric cancer (GC).</div></div><div><h3>Patients and methods</h3><div>We investigated 400 patients who received systemic chemotherapy for unresectable, metastatic, or recurrent GC. Immunohistochemistry for CLDN18 (43-14A), human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and fibroblast growth factor receptor 2, as well as HER2 silver <em>in situ</em> hybridization (ISH), Epstein–Barr virus (EBV) ISH, and microsatellite instability testing were carried out. CD3+, CD8+, CD4+, and Foxp3-positive immune cell densities were calculated using digital image analysis.</div></div><div><h3>Results</h3><div>In GC cases with any CLDN18.2 expression, more than half of the cases (61.3%) showed different expression results between four different tissue microarray (TMA) cores. When comparing CLDN18.2 status between whole tissue sections and the combined results from the four TMA cores, discrepancies were observed in only 2 out of 85 GC cases (2.4%), with 1 false positive and 1 false negative. After considering intratumoral heterogeneity, a CLDN18.2 positivity rate of 31.3% was observed among the 400 GC patients. CLDN18.2 positivity was rare in GCs located in the antrum (or lower third) and in HER2-positive cases but was common in EBV-positive GCs (<em>P</em> &lt; 0.05). No differences in overall survival (OS) were observed according to CLDN18.2 positivity (<em>P</em> = 0.116). Additionally, there was no association between OS and CLDN18.2 positivity in patients treated with fluoropyrimidine plus platinum, chemotherapy plus trastuzumab, paclitaxel with or without ramucirumab, and immuno-oncologic agents. CLDN18.2-positive/PD-L1-high GCs showed statistically significantly longer OS than others (<em>P</em> = 0.025) and higher CD8+ T-cell densities in both the tumor center and periphery (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Characterizing unresectable, metastatic, or recurrent GC with positive CLDN18.2 expression and evaluating intratumoral heterogeneity and prognostic implications of various therapeutics help advance treatment strategies and develop new therapies for patients with GC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 104000"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746184","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":"Atezolizumab monotherapy for metastatic urothelial carcinoma: final analysis from the phase II IMvigor210 trial","authors":"J.E. Rosenberg ,&nbsp;M.D. Galsky ,&nbsp;T. Powles ,&nbsp;D.P. Petrylak ,&nbsp;J. Bellmunt ,&nbsp;Y. Loriot ,&nbsp;A. Necchi ,&nbsp;J. Hoffman-Censits ,&nbsp;J.L. Perez-Gracia ,&nbsp;M.S. van der Heijden ,&nbsp;R. Dreicer ,&nbsp;I. Durán ,&nbsp;D. Castellano ,&nbsp;A. Drakaki ,&nbsp;M. Retz ,&nbsp;S.S. Sridhar ,&nbsp;P. Grivas ,&nbsp;E.Y. Yu ,&nbsp;P.H. O’Donnell ,&nbsp;H.A. Burris ,&nbsp;D. Bajorin","doi":"10.1016/j.esmoop.2024.103972","DOIUrl":"10.1016/j.esmoop.2024.103972","url":null,"abstract":"<div><h3>Background</h3><div>The IMvigor210 trial demonstrated clinical benefit and manageable toxicity with atezolizumab monotherapy [anti-programmed death-ligand 1 (PD-L1)] in patients with metastatic urothelial carcinoma (UC) in primary analyses. Final efficacy and safety results after long-term follow-up are reported.</div></div><div><h3>Patients and methods</h3><div>This phase II single-arm trial of atezolizumab monotherapy in patients with advanced UC included two cohorts: untreated patients ineligible for cisplatin-based chemotherapy (cohort 1; <em>n</em> = 119) and those previously treated with platinum-based chemotherapy (cohort 2; <em>n</em> = 310). Atezolizumab was administered i.v. (1200 mg every 21 days) until progression or unacceptable toxicity. Primary endpoints were independent review facility-assessed confirmed objective response rate (ORR) per RECIST 1.1 in cohort 1 and independent review facility-assessed ORR per RECIST 1.1 and investigator-assessed modified (m)RECIST in cohort 2. Overall survival (OS), efficacy by PD-L1 status, and safety were also assessed.</div></div><div><h3>Results</h3><div>At data cut-off (1 June 2023), the median survival follow-up was 96.4 months (range, 0.2-103.4 months) in cohort 1 and 46.2 months [0.2 (censored)-54.9 months] in cohort 2. In cohort 1, the ORR [95% confidence interval (CI)] was 23.5% (16.2% to 32.2%) in all patients and 28.1% (13.8% to 46.8%) in the PD-L1 tumor-infiltrating immune cell (IC)2/3 subgroup. Median OS (95% CI) was 16.3 months (10.4-24.5 months) overall and 12.3 months (6.0-49.8 months) in the PD-L1 IC2/3 subgroup. In cohort 2, the ORR (95% CI) was 16.5% (12.5% to 21.1%) per RECIST 1.1 and 19.7% (95% CI 15.4% to 24.6%) per mRECIST in all patients and 27.0% (18.6% to 36.8%) and 28.0% (19.5% to 37.9%), respectively, in the PD-L1 IC2/3 subgroup. Median OS (95% CI) was 7.9 months (6.7-9.3 months) in all patients and 11.9 months (9.0-22.8 months) in the IC2/3 subgroup. Treatment-related grade 3/4 adverse events occurred in 21.8% (cohort 1) and 18.7% (cohort 2); one treatment-related death occurred in cohort 1.</div></div><div><h3>Conclusions</h3><div>With long-term follow-up, atezolizumab monotherapy demonstrated clinically meaningful efficacy with durable responses in a subset of patients with metastatic UC; there were no new safety signals.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103972"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791333","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}