ESMO Open最新文献

{"title":"Survival outcomes of young-age female patients with early breast cancer: an international multicenter cohort study","authors":"","doi":"10.1016/j.esmoop.2024.103732","DOIUrl":"10.1016/j.esmoop.2024.103732","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of breast cancer among young Asian women is increasing, yet they remain underrepresented in global data. We analyzed the epidemiology and outcomes of Asian patients with breast cancer &lt;40 years old across different subtypes to identify their clinical unmet needs.</div></div><div><h3>Patients and methods</h3><div>Female patients aged ≥20 years diagnosed with early breast cancer were analyzed from the prospective cohort of the Asian Breast Cancer Cooperative Group (ABCCG). For comparison, data from the Surveillance, Epidemiology, and End Results Program (SEER) cancer registry were used. Patients were categorized into three age groups: young (&lt;40 years), alleged premenopausal mid-age (40-49 years), and alleged postmenopausal (aged ≥50 years). Multivariable Cox proportional hazards models for survival were adjusted for subtypes, histologic grade, T stage, nodal status, and study centers.</div></div><div><h3>Results</h3><div>A total of 45 021 patients with breast cancer from Asian study centers, 496 332 SEER-White patients, and 18 279 SEER-Asian patients were included in the analysis. The median age at diagnosis was younger in the Asian cohort (51 years) compared with SEER-Whites (62 years) and SEER-Asians (58 years; <em>P</em> &lt; 0.0001). In the young-age group, hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) breast cancer was more prevalent among Asians and SEER-Asians compared with SEER-Whites (61.2% and 59.8% versus 54.7%). In the Asian population, young patients with HR+/HER2− breast cancer exhibited significantly inferior overall survival than the mid-age group (6-year overall survival 94.4% versus 96.6%; mid-age to young-age group hazard ratio 0.62; <em>P</em> &lt; 0.001). Similarly, young patients in SEER-Whites showed an earlier decline in survival compared with the mid-age group (89.1% versus 94.0%; <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>ABCCG-Asian patients with breast cancer &lt;40 years old with HR+/HER2− subtypes were more likely to have worse survival outcomes than their mid-age counterparts. Our study highlights the poorer prognosis of young patients and underscores the need for a tailored therapeutic approach, such as ovarian function suppression, particularly considering ethnic factors.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442646","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":"Breast cancer in adolescents and young adults has a specific biology and poor patient outcome compared with older patients","authors":"","doi":"10.1016/j.esmoop.2024.103737","DOIUrl":"10.1016/j.esmoop.2024.103737","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to clarify the features of adolescents and young adults (AYA: younger than 40 years old) breast cancer (BC) compared with other age groups in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC, given the effects of age-related hormonal status.</div></div><div><h3>Methods</h3><div>The cohorts analyzed were divided into AYA (15-39 years old), perimenopausal (40-54 years old), menopausal (55-64 years old), and old (65+ years old). Clinicopathological and biological features were analyzed using gene set variation analysis and xCell algorithm using transcriptome profiles from large public databases of ER-positive/HER2-negative BC (METABRIC; <em>n</em> = 1353, SCAN-B; <em>n</em> = 2381).</div></div><div><h3>Results</h3><div>In the ER-positive/HER2-negative subtype, pathological lymph node positivity, and Nottingham grade 3 were higher among AYA (all <em>P</em> &lt; 0.001). AYA patients had a trend toward worse disease-specific and overall survival, particularly compared with the perimenopausal group. Estrogen response late signaling decreased with age (all <em>P</em> ≤ 0.001 in both METABRIC and SCAN-B cohorts). AYA was associated with significantly higher BRCAness and DNA repair than the other groups (all <em>P</em> &lt; 0.05 in both cohorts). AYA significantly enriched cell proliferation-related and procancerous gene sets [mTORC1, unfolded protein response, and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling] when compared with the others (all <em>P</em> &lt; 0.03 in both cohorts). Interestingly, these features have also been observed in tumors &lt;2 cm. Infiltration of CD8⁺, regulatory, T helper type 2 cells, and M1 macrophages was higher, while M2 macrophages were lower in AYA (all <em>P</em> &lt; 0.03 in both cohorts). Finally, ER-positive/HER2-negative BC in AYA patients has different features of gene mutations, including <em>AHNAK2</em>, <em>GATA3</em>, <em>HERC2</em>, and <em>TG</em>, which were observed at a higher rate in AYA, and <em>KMT2C</em>, which was observed at a lower rate in AYA, compared with other age groups.</div></div><div><h3>Conclusions</h3><div>ER-positive/HER2-negative BC in AYA was highly proliferative with high immune cell infiltration compared with the other age groups.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432026","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 microenvironment modulation following neoadjuvant therapy for oesophageal adenocarcinoma: a translational analysis of the DEBIOC clinical trial","authors":"","doi":"10.1016/j.esmoop.2024.103930","DOIUrl":"10.1016/j.esmoop.2024.103930","url":null,"abstract":"<div><h3>Background</h3><div>The Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC) trial reported an acceptable safety profile for neoadjuvant oxaliplatin and capecitabine (Xelox) ± AZD8931 in oesophageal adenocarcinoma (OAC) but limited efficacy. We evaluated the impact of neoadjuvant Xelox ± AZD8931, a novel small-molecule inhibitor with equipotent activity against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2 and HER3, on biological pathways using a unique software-driven solution.</div></div><div><h3>Patients and methods</h3><div>Transcriptomic profiles from 25 pre-treatment formalin-fixed paraffin-embedded OAC biopsies and 18 matched resection specimens, treated with Xelox + AZD8931 (<em>n</em> = 16) and Xelox alone (<em>n</em> = 9), were analysed using the Almac clara^T total mRNA report analysing 92 gene signatures, 100 unique single-gene drug targets and 7337 single genes across 10 hallmarks of cancer. Gene-set enrichment analysis (GSEA) was utilised to investigate pathways governing pathological response. Tumour-infiltrating lymphocytes (TILs) were assessed digitally using the QuPath software.</div></div><div><h3>Results</h3><div>Hierarchical clustering identified three molecular subgroups classified by activation of innate immune signalling. The immune-high subgroup was associated with HER2 positivity, increased pathological response and a marked reduction in immune signalling and TILs following neoadjuvant therapy. The immune-low cluster was predominantly HER2/EGFR-negative, and EGFR positivity was associated with the immune-mixed subgroup. Treatment with neoadjuvant therapy induced common resistance mechanisms, such as angiogenesis and epithelial–mesenchymal transition signalling, and a reduction in DNA repair signatures. Addition of AZD8931 was associated with reduction of expression of EGFR, HER2 and AKT pathways and also promoted an immunosuppressive microenvironment. GSEA showed that patients with a pathological response to treatment had increased immune signalling, whereas non-responders to neoadjuvant therapy were enriched for nucleotide repair and cellular growth through the action of E2F transcription factors.</div></div><div><h3>Conclusion</h3><div>OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2-positive/immune-high tumours.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423522","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":"Fruquintinib in refractory metastatic colorectal cancer: a multicenter real-world study","authors":"","doi":"10.1016/j.esmoop.2024.103702","DOIUrl":"10.1016/j.esmoop.2024.103702","url":null,"abstract":"<div><h3>Background</h3><div>Fruquintinib has been approved by the Food and Drug Administration for refractory metastatic colorectal cancer (mCRC). In clinical practice, fruquintinib is sometimes used in combination with other drugs, but its efficacy and safety are still unknown. In this study, we present a comprehensive analysis of the real-world treatment modalities involving fruquintinib in late-line settings for mCRC across six centers in China.</div></div><div><h3>Patients and methods</h3><div>Patients with refractory mCRC who received fruquintinib treatment in six centers in China between 1 January 2021 and 31 June 2022 were included in this study. Patients were categorized into two cohorts: the monotherapy group (treated solely with fruquintinib) and the combined group (received fruquintinib combined with chemotherapy and/or anti-programmed cell death protein 1 antibodies). Demographic, clinical, survival, and safety data were retrospectively analyzed. The study was registered at <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> as NCT06202417.</div></div><div><h3>Results</h3><div>A total of 520 patients were included in this study. The median follow-up time was 9.7 months. The disease control rate was 64.8%. The median progression-free survival was 5.0 months and the median overall survival was 11.4 months. Of them, 387 (74.4%) were treated with fruquintinib alone, while 133 (25.6%) were administered fruquintinib plus chemotherapy and/or anti-programmed cell death protein 1 antibodies, respectively. Adverse events were reported by 91.3% (457/520) of patients. The rate of grade 3 or 4 toxicity was 42.4% (237/520). No treatment-related death occurred.</div></div><div><h3>Conclusion</h3><div>Fruquintinib, either as a standalone treatment or in combination with other medications, demonstrates substantial efficacy and favorable tolerability in refractory mCRC patients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423523","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":"Clinical relevance of reports on early access programs for checkpoint inhibitors in cancer patients: a French retrospective nationwide cohort study","authors":"","doi":"10.1016/j.esmoop.2024.103711","DOIUrl":"10.1016/j.esmoop.2024.103711","url":null,"abstract":"<div><h3>Background</h3><div>To accelerate access to new drugs, France operated an early access program known as Temporary Authorizations for Use (ATUs) until 2021. We analyzed clinical reports submitted under ATUs for immune checkpoint inhibitors (ICIs) and assessed their clinical relevance regarding the approval of ICIs in oncology.</div></div><div><h3>Methods</h3><div>We included all ICIs granted an ATU by the French drug safety agency, Agence nationale de sécurité du médicament et des produits de santé (ANSM; French National Agency for the Safety of Medicines and Health Products), for patients with cancer between 1 January 2010 and 31 December 2020. We collected patients’ clinical and pharmacovigilance data from ATU reports submitted by pharmaceutical companies and compared these data with those from corresponding pivotal clinical trials (CTs).</div></div><div><h3>Results</h3><div>The ATUs provided early access to 5807 patients with seven ICIs across 11 cancer indications, 1 of which had no corresponding ATU report. Of the 10 available ATU reports, only 1 included all required data. Clinical follow-up forms were available for 40.5% of patients. Differences in data reporting prevented us from comparing serious adverse events between the CTs and ATU reports. Clinicians and pharmaceutical companies often disagreed on whether ICIs caused 163 permanent treatment discontinuations, with Cohen’s bias- and prevalence-adjusted <em>κ</em> = 0.52, 95% CI 0.33-0.68. Although agreement was almost perfect for 93 nonprogressive tumor deaths (<em>κ</em> = 0.88, 95% CI 0.66-0.97), 29% of ATU patient deaths remained unexplained and were reported as unrelated to treatment by the pharmaceutical companies.</div></div><div><h3>Conclusion</h3><div>French ATUs facilitated early access to new ICIs for many patients with cancer. However, data attrition hindered effective real-world monitoring.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423521","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":"Clinically meaningful outcomes in refractory metastatic colorectal cancer: a decade of defining and raising the bar","authors":"","doi":"10.1016/j.esmoop.2024.103931","DOIUrl":"10.1016/j.esmoop.2024.103931","url":null,"abstract":"<div><div>Currently, there is no consensus definition for clinically meaningful outcomes in randomized clinical trials (RCTs) designed to evaluate new treatments for patients with refractory metastatic colorectal cancer (mCRC). Since 2014, recommended targets for improvements in overall survival and progression-free survival have been published by several societies, including those from the American Society of Clinical Oncology (ASCO) Clinically Meaningful Outcomes Working Group in 2014, the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) in 2015, and Colorectal Cancer Canada (CCC) consensus statements in 2019. However, evidence from several systematic reviews suggests that in a substantial proportion of RCTs that led to oncology drug approvals, the recommended thresholds of ASCO and ESMO-MCBS were not met. In addition to efficacy and safety, quality of life (QoL) is important to patients with mCRC, especially for those who are receiving later-line therapy or end-of-life care. As such, both ESMO-MCBS and CCC recommend the inclusion of QoL assessments in the design of mCRC clinical trials. Since the publication of the ASCO recommendations in 2014, there has been significant progress in the development of treatment options for patients with refractory mCRC; these include the approvals of trifluridine/tipiracil (FTD/TPI) as a single agent and in combination with bevacizumab, and the approval of fruquintinib. Among the phase III RCTs in third-line mCRC, only the SUNLIGHT trial of FTD/TPI plus bevacizumab met all recommended thresholds for clinically meaningful improvements, while also demonstrating a manageable safety profile and slower deterioration in multiple measures of QoL compared with FTD/TPI alone. The results from the SUNLIGHT study show that incremental gains in several clinically meaningful endpoints are achievable, thus raising the bar in defining clinically meaningful outcomes for emerging therapies in refractory mCRC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423524","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":"MAP 2024 Officers and Organisation","authors":"","doi":"10.1016/S2059-7029(24)01725-3","DOIUrl":"10.1016/S2059-7029(24)01725-3","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525796","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":"23P Unraveling predictive transcriptomic signatures of anti-EGFR therapy response in RAS/BRAF wild-type metastatic colorectal cancer","authors":"","doi":"10.1016/j.esmoop.2024.103769","DOIUrl":"10.1016/j.esmoop.2024.103769","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525910","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":"82P Applying computational approaches to build a predictive protein structure and discover novel inhibitors for mitotic serine/threonine kinase BUB1B","authors":"","doi":"10.1016/j.esmoop.2024.103823","DOIUrl":"10.1016/j.esmoop.2024.103823","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526201","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":"20P Distinctive genomic profile of lymph node profile and distant metastasis in papillary thyroid cancer","authors":"","doi":"10.1016/j.esmoop.2024.103766","DOIUrl":"10.1016/j.esmoop.2024.103766","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525907","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}