ESMO Open最新文献

{"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":"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, M D Galsky, T Powles, D P Petrylak, J Bellmunt, Y Loriot, A Necchi, J Hoffman-Censits, J L Perez-Gracia, M S van der Heijden, R Dreicer, I Durán, D Castellano, A Drakaki, M Retz, S S Sridhar, P Grivas, E Y Yu, P H O'Donnell, H A Burris, S Mariathasan, Y Shi, E Goluboff, D Bajorin","doi":"10.1016/j.esmoop.2024.103972","DOIUrl":"10.1016/j.esmoop.2024.103972","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Patients and methods: </strong>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; n = 119) and those previously treated with platinum-based chemotherapy (cohort 2; n = 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"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}

{"title":"Sex differences in the pharmacokinetics of anticancer drugs: a systematic review.","authors":"J Delahousse, A D Wagner, S Borchmann, A A Adjei, J Haanen, F Burgers, A Letsch, A Quaas, S Oertelt-Prigione, B C Özdemir, R H A Verhoeven, O Della Pasqua, A Paci, O Mir","doi":"10.1016/j.esmoop.2024.104002","DOIUrl":"10.1016/j.esmoop.2024.104002","url":null,"abstract":"<p><strong>Background: </strong>In addition to the effect of body weight, a patient's sex can influence the pharmacokinetics (PK) of anticancer agents, and thereby their activity and safety. The magnitude and relevance of sex differences, however, are currently unclear.</p><p><strong>Methods: </strong>We carried out a systematic review of published studies (clinical, n ≥ 10) on Food and Drug Administration (FDA)-approved (on 31 January 2022) anticancer drugs (excluding hormonal agents), aiming to identify significant PK differences between male and female patients. A difference of ≥20% on PK parameters (clearance or trough concentration) was considered significant. The methodological quality was assessed using the National Institutes of Health study quality assessment tool. This systematic review was conducted according to the PRISMA2020 guidelines and a previously published protocol, which was registered in the PROSPERO database (number 291008).</p><p><strong>Results: </strong>Data on 99 anticancer agents (for a total of 1643 abstracts and European Medicines Agency/FDA documents) were screened. The final dataset included 112 articles and 8 European Medicines Agency/FDA documents. The median size of a study cohort was 445 patients (range: 12-6468 patients). Significant PK differences (>+20% in clearance or apparent clearance in women) were identified for 14 drugs, and potentially significant PK differences (due to conflicting reports) for another 8 drugs. None of the studies included sex-based summaries to assess whether the observed differences in PK may impact the efficacy or safety profile.</p><p><strong>Conclusions: </strong>Significant sex differences in PK have been identified including commonly used drugs of different classes, such as 5-fluorouracil, doxorubicin, paclitaxel, regorafenib, atezolizumab, and temozolomide. The risk-benefit ratio for such anticancer drugs is likely to be improved by the development of sex-specific dosing strategies. Additional sex-based PK-pharmacodynamic analyses are recommended during dose optimisation and are to be conducted in line with the FDA Project Optimus guidance. They should be reported even if no association between the patients' sex and the activity and/or toxicity of an anticancer drug has been identified.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"104002"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812681","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":"Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer","authors":"S.-H. Lee ,&nbsp;J. Menis ,&nbsp;T.M. Kim ,&nbsp;H.R. Kim ,&nbsp;C. Zhou ,&nbsp;S.A. Kurniawati ,&nbsp;K. Prabhash ,&nbsp;H. Hayashi ,&nbsp;D.D.-W. Lee ,&nbsp;M.S. Imasa ,&nbsp;Y.L. Teh ,&nbsp;J.C.-H. Yang ,&nbsp;T. Reungwetwattana ,&nbsp;V. Sriuranpong ,&nbsp;C.-E. Wu ,&nbsp;Y. Ang ,&nbsp;M. Sabando ,&nbsp;M. Thiagarajan ,&nbsp;H. Mizugaki ,&nbsp;V. Noronha ,&nbsp;S. Popat","doi":"10.1016/j.esmoop.2024.103996","DOIUrl":"10.1016/j.esmoop.2024.103996","url":null,"abstract":"<div><div>The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer (mNSCLC), published in January 2023, was modified according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with oncogene-addicted mNSCLC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with oncogene-addicted mNSCLC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Korean Society for Medical Oncology (KSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with oncogene-addicted mNSCLC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, while respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies between the different regions of Asia.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103996"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746182","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":"Measuring financial distress in German cancer patients: development and validation of the Financial Distress of Cancer Assessment Tool (FIAT)","authors":"L. Richter ,&nbsp;S. Pauge ,&nbsp;K. Mehlis ,&nbsp;A. Zueger ,&nbsp;B. Surmann ,&nbsp;V. Mathies ,&nbsp;W. Greiner ,&nbsp;T. Ernst ,&nbsp;E.C. Winkler ,&nbsp;N. Menold","doi":"10.1016/j.esmoop.2024.103992","DOIUrl":"10.1016/j.esmoop.2024.103992","url":null,"abstract":"<div><h3>Background</h3><div>Cancer diagnosis and therapy can lead to significant financial distress for those affected, even in universal health care systems. We present the development and validation of a patient-reported outcome measure for financial distress in German cancer patients.</div></div><div><h3>Methods</h3><div>Validation of the newly developed instrument followed a two-step approach, including two quantitative paper–pencil surveys (<em>N1</em> = 111, <em>N2</em> = 267) with patients of all types of cancer and treatment status at two German university hospitals. Factorial validity, reliability, construct, and criterion validity were assessed using exploratory and confirmatory factor analysis, correlative and linear regression analysis.</div></div><div><h3>Results</h3><div>The Financial Distress of Cancer Assessment Tool (FIAT) comprises 19 items across three domains of subjective financial distress: (i) financial worries; (ii) dissatisfaction across various life domains, and (iii) challenging experiences with authorities and benefit providers (e.g. employment agency, health insurance). Confirmatory factor analysis confirmed the instrument’s factorial structure. Composite reliability (Raykov’s rho) ranges from 0.88 to 0.96, and retest reliability ranges from 0.64 to 0.75. Correlational analyses showed significant associations between FIAT scores and related constructs [e.g. correlations with the EORTC-QLQ-C30 financial distress subscale (Q28) ranging from 0.47 to 0.60], supporting its construct validity. Additionally, higher FIAT scores were significantly associated with lower health-related quality of life measured by Q29 and Q30 of the EORTC-QLQ-C30, with correlations ranging from −0.21 to −0.28. They were also positively correlated with depression (PHQ-4), with correlations ranging from 0.33 to 0.45, and anxiety (PHQ-4) with correlations ranging from 0.25 to 0.36, confirming its criterion validity.</div></div><div><h3>Conclusions</h3><div>The newly developed patient-reported outcome measure is the first reported measurement tool to assess financial distress in German cancer patients. The instrument can be used for research purposes and to enable the provision of coordinated support services.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103992"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746185","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":"Surface-based deep inspiration breath-hold radiotherapy in left-sided breast cancer: final results from the SAVE-HEART study.","authors":"S Schönecker, L Angelini, A Gaasch, A Zinn, D Konnerth, C Heinz, Y Xiong, K Unger, G Landry, I Meattini, M Braun, M Pölcher, N Harbeck, R Würstlein, M Niyazi, C Belka, M Pazos, S Corradini","doi":"10.1016/j.esmoop.2024.103993","DOIUrl":"10.1016/j.esmoop.2024.103993","url":null,"abstract":"<p><strong>Background: </strong>Adjuvant radiotherapy (RT) plays an essential role in the management of early breast cancer (BC), but can lead to cardiovascular and lung toxicities. RT in deep inspiration breath hold (DIBH) often allows better protection of organs at risk. This prospective study compares surface-guided DIBH with free breathing (FB) in patients with left-sided BC, by evaluating individual cardiovascular risks and treatment plan dosimetry.</p><p><strong>Patients and methods: </strong>The study enrolled 585 patients from October 2016 to January 2021 with left-sided invasive breast carcinoma with indicated adjuvant RT of the breast/thoracic wall with or without regional lymph nodes. The ability to hold breath for 20 s was a prerequisite. The treatments were either hypofractionated (HF; 40.05 Gy/15Fx) or normofractionated (NF; 50.00 Gy/25Fx). DIBH was applied using the automatically triggered surface guidance system Catalyst with audio-video feedback. Computed tomography and surface data were acquired during both DIBH and FB. The primary endpoint of the study was the comparative evaluation of heart dose reduction using DIBH.</p><p><strong>Results: </strong>Plan dosimetry was significantly improved by DIBH. The mean and maximum doses to the heart and the left coronary artery were significantly reduced by 36%-42% in HF and NF plans (P < 0.001), while the mean ipsilateral lung dose was reduced by 12%-14% (P < 0.001). Furthermore, DIBH resulted in a 5% reduction in the cumulative 10-year cardiovascular disease risk (10-year cardiovascular disease risk) compared with FB (3.59% to 3.41%; P < 0.001).</p><p><strong>Conclusion: </strong>To the best of our knowledge, this is the largest prospective study showing better sparing for cardiac and ipsilateral lung doses with surface-guided DIBH compared with FB in patients with left-sided BC.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"103993"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779658","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":"Practical treatment strategies and novel therapies in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) advanced breast cancer.","authors":"K Fanucci, A Giordano, T Erick, S M Tolaney, S Sammons","doi":"10.1016/j.esmoop.2024.103997","DOIUrl":"10.1016/j.esmoop.2024.103997","url":null,"abstract":"<p><p>Mutations in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway occur in 30%-40% of patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer. For most patients, endocrine therapy with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor is the first-line treatment. Recent studies indicate that adding inavolisib, a PI3Kα inhibitor, to palbociclib/fulvestrant benefits patients with endocrine-resistant HR+/HER2- metastatic breast cancer with a PIK3CA mutation. Alpelisib and capivasertib are both US Food and Drug Administration (FDA) approved in combination with fulvestrant in patients with endocrine-resistant HR+/HER2-, PIK3CA-mutant metastatic breast cancer, both with activity in the post-CDK4/6 setting. Capivasertib added to fulvestrant is the first AKT inhibitor to show a significant progression-free survival benefit with a trend for overall survival benefit and the only approved option for patients with phosphate and tensin homolog (PTEN) or AKT alterations. Toxicity profiles of all agents necessitate careful patient selection. Several mutant-selective and pan-mutant-selective novel inhibitors are under investigation with the potential to improve tolerability and efficacy.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"103997"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823923","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":"Use and outcomes of trastuzumab deruxtecan in HER2-positive and HER2-low metastatic breast cancer in a real-world setting: a nationwide cohort study.","authors":"H Jourdain, A Di Meglio, I Mansouri, D Desplas, M Zureik, N Haddy","doi":"10.1016/j.esmoop.2024.104083","DOIUrl":"10.1016/j.esmoop.2024.104083","url":null,"abstract":"<p><strong>Background: </strong>Since 2020, trastuzumab deruxtecan (T-DXd) has been used in France for patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive or HER2-low metastatic breast cancer (mBC). We aimed to describe the clinical characteristics, outcomes, and potential toxicities among patients receiving T-DXd for HER2-positive and HER2-low mBC.</p><p><strong>Patients and methods: </strong>Using the French National Health Data System (SNDS), we identified patients who initiated T-DXd for mBC from 30 September 2020 to 30 September 2023. Follow-up data were available through 31 December 2023. Patients were categorized into three groups according to HER2 expression and line of treatment: HER2-positive mBC receiving T-DXd in the third (HER2+ 3L) or second line (HER2+ 2L) and HER2-low mBC receiving T-DXd in the second line (HER2-low2L). We describe their characteristics and report the Kaplan-Meier estimates of overall survival (OS) and incidence of hospitalization.</p><p><strong>Results: </strong>The cohort comprised 5890 patients, including 2010 (34.1%) HER2+ 3L, 1260 (21.4%) HER2+ 2L, and 2620 (44.5%) HER2-low2L. For the three respective groups, the median age at inclusion was 59 years [interquartile range (IQR) 51-69 years], 59 years (50-68 years), and 61 years (52-70 years); 34.8%, 30.2%, and 16.0% had brain metastases; 14.2%, 13.7%, and 13.4% had a current or history of cardiovascular disease. Median OS was 30.2 months [95% confidence interval (CI) 28.1-33.5 months] for HER2+ 3L patients, was not reached for HER2+ 2L patients, and was 16.8 months (95% CI 14.5 months-not reached) for HER2-low2L patients. The incidence of hospitalization for cardiac, respiratory, digestive, and hematological disorders was similar for HER2-positive patients treated in the second or third line, whereas HER2-low patients had higher incidence rates for these events.</p><p><strong>Conclusion: </strong>In this large French observational study, T-DXd users were older, had more comorbidities, and had more brain metastases than patients included in registration trials. The rapid expansion of clinical indications of T-DXd calls for proactive surveillance and timely management of potentially life-threatening T-DXd-related toxicity.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"104083"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812682","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":"Identifying predictors of treatment response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-negative breast cancer: the NEOENDO translational study☆","authors":"F. Schettini ,&nbsp;F. Brasó-Maristany ,&nbsp;T. Pascual ,&nbsp;N. Lorman-Carbó ,&nbsp;S. Nucera ,&nbsp;M. Bergamino ,&nbsp;P. Galván ,&nbsp;B. Conte ,&nbsp;E. Seguí ,&nbsp;I. García Fructuoso ,&nbsp;R. Gómez Bravo ,&nbsp;A.B. Rodríguez ,&nbsp;O. Martínez-Sáez ,&nbsp;N. Chic ,&nbsp;M. Vidal ,&nbsp;B. Adamo ,&nbsp;B. González-Farre ,&nbsp;E. Sanfeliu ,&nbsp;I. Cebrecos ,&nbsp;E. Mensión ,&nbsp;A. Prat","doi":"10.1016/j.esmoop.2024.103989","DOIUrl":"10.1016/j.esmoop.2024.103989","url":null,"abstract":"<div><h3>Background</h3><div>Predictors of response to neoadjuvant chemotherapy (NACT) and endocrine therapy (NET) in hormone receptor-positive (HoR+)/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) are required. Also, pathological and molecular changes induced by both strategies and their impact on patients’ outcomes have not been reported so far.</div></div><div><h3>Patients and methods</h3><div>In a cohort of 186 patients with early-stage HoR+/HER2-negative BC treated with NACT or NET, we assessed the association of baseline main clinicopathological features and PAM50 gene expression (GE), intrinsic subtypes (IS) and risk-of-relapse (ROR-P) score with pathological outcomes according to treatment strategy. Molecular NACT/NET-induced changes were described and compared, along with their associations with event-free survival (EFS). Comparison of the two cohorts after propensity score matching (PSM) was used as sensitivity analysis. Molecular changes were confirmed in cell lines.</div></div><div><h3>Results</h3><div>NACT was associated with higher rates of residual cancer burden (RCB)-0/I than NET in the overall population (38.2% versus 13.5%, <em>P</em> &lt; 0.001) and after PSM (<em>P</em> = 0.036). PAM50 non-luminal IS were the only independent and positive predictor of RCB-0/I (<em>P</em> = 0.024) in the NACT cohort, while <em>MMP11</em> messenger RNA levels were the only independent and negative predictor (<em>P</em> = 0.014) in the NET cohort. Both treatments shifted the tumor types toward less aggressive forms (i.e. PAM50 luminal A/normal-like), lowered the risk of recurrence in terms of ROR-P, up-regulated selected immune genes and PAM50 basal-like-related genes/signature and significantly downregulated proliferation-/luminal-/HER2-related genes/signatures, though NACT more than NET. Molecular findings were confirmed after PSM. A net reduction in proliferation-related genes and ROR-P was confirmed in cell lines with chemotherapy and endocrine therapy. Different baseline molecular features associated with diverse kind of responses (ROR-P downstaging, Ki67 reduction or pathological responses) with NACT and NET. Decreasing ROR-P and transitioning the tumor subtype to resemble normal tissue (i.e. PAM50 normal-like) suggested improved EFS.</div></div><div><h3>Conclusions</h3><div>NACT was more effective in the molecular and dimensional tumor ‘downstaging’ than NET but baseline molecular features associated with differential responses according to treatment strategy. Examining baseline and post-treatment GE might help tailor more personalized and effective care.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103989"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720974","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}