ESMO Open最新文献

{"title":"Is pathological response an adequate surrogate marker for survival in neoadjuvant therapy with immune checkpoint inhibitors?","authors":"K. Sugiyama ,&nbsp;A. Gordon ,&nbsp;S. Popat ,&nbsp;A. Okines ,&nbsp;J. Larkin ,&nbsp;I. Chau","doi":"10.1016/j.esmoop.2024.104122","DOIUrl":"10.1016/j.esmoop.2024.104122","url":null,"abstract":"<div><div>Pathological response (PR) is an oncological outcome measure that indicates the therapeutic response to neoadjuvant therapy. In clinical trials involving neoadjuvant or perioperative interventions, overall survival and disease/event-free survival are typically the primary outcome measures. Although some evidence suggests that pathological complete response (pCR) can serve as a surrogate marker for the primary endpoint in prospective trials, it remains uncertain whether pCR is a true surrogate marker for patients with cancer undergoing curative resection across all solid tumours. Here, we review the role of PR as a surrogate marker and its associated methodological issues in the era of perioperative immune checkpoint inhibitors.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104122"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058493","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":"Liver metastases do not predict resistance to the addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab in proficient MMR metastatic colorectal cancer: a secondary analysis of the AtezoTRIBE study","authors":"C. Antoniotti ,&nbsp;M. Carullo ,&nbsp;D. Rossini ,&nbsp;F. Pietrantonio ,&nbsp;L. Salvatore ,&nbsp;S. Lonardi ,&nbsp;S. Tamberi ,&nbsp;C. Sciortino ,&nbsp;V. Conca ,&nbsp;M.A. Calegari ,&nbsp;P. Ciracì ,&nbsp;E. Tamburini ,&nbsp;F. Bergamo ,&nbsp;C. Boccaccio ,&nbsp;A. Passardi ,&nbsp;G. Ritorto ,&nbsp;C. Ugolini ,&nbsp;G. Aprile ,&nbsp;J. Galon ,&nbsp;C. Cremolini","doi":"10.1016/j.esmoop.2025.104135","DOIUrl":"10.1016/j.esmoop.2025.104135","url":null,"abstract":"<div><h3>Background</h3><div>Liver metastases (LMs) are related to poor efficacy of immune checkpoint inhibitor (ICI)-containing therapies. In the AtezoTRIBE trial, Immunoscore-Immune-Checkpoint (immunoscore-IC) was a predictor of benefit from atezolizumab in mismatch repair-proficient (pMMR) metastatic colorectal cancer (mCRC).</div></div><div><h3>Patients and methods</h3><div>In pMMR patients enrolled in the AtezoTRIBE study, we investigated the association of LMs with immune-related biomarkers and treatment outcomes, and the predictive role of immunoscore-IC in the LMs group.</div></div><div><h3>Results</h3><div>Out of 202 pMMR patients, 151 (75%) had LMs. No differences in immune-related features were observed according to the presence or not of LMs, except for a lower prevalence of tumour-infiltrating lymphocytes-high tumours in the LMs group (33% versus 52%, <em>P</em> = 0.03). Worse outcomes were observed among patients with LMs [progression-free survival (PFS), <em>P</em> = 0.002; overall survival (OS), <em>P</em> = 0.011], also in multivariable models. The effect of adding atezolizumab to FOLFOXIRI/bevacizumab was independent from LMs in terms of PFS (<em>P</em>_int = 0.990) and OS (<em>P</em>_int = 0.800). Among patients with pMMR mCRC and LMs, those with immunoscore-IC-high but not those with immunoscore-IC-low tumours achieved benefit from atezolizumab, though in the absence of a statistically significant interaction effect (<em>P</em>_int for PFS and OS = 0.166 and 0.473, respectively).</div></div><div><h3>Conclusions</h3><div>LMs are associated with poor prognosis in pMMR mCRC and do not predict resistance to the addition of atezolizumab to FOLFOXIRI/bevacizumab. Immunoscore-IC seems to retain its predictive impact also among patients with LMs.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104135"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143133020","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":"An open-label, phase IB/II study of abemaciclib with paclitaxel for tumors with CDK4/6 pathway genomic alterations","authors":"K.H. Kim ,&nbsp;C. Park ,&nbsp;S.-H. Beom ,&nbsp;M.H. Kim ,&nbsp;C.G. Kim ,&nbsp;H.R. Kim ,&nbsp;M. Jung ,&nbsp;S.J. Shin ,&nbsp;S.Y. Rha ,&nbsp;H.S. Kim","doi":"10.1016/j.esmoop.2024.104106","DOIUrl":"10.1016/j.esmoop.2024.104106","url":null,"abstract":"<div><h3>Background</h3><div>Disruption of cyclin D-dependent kinases (CDKs), particularly <em>CDK4/6</em>, drives cancer cell proliferation via abnormal protein phosphorylation. This open-label, single-arm, phase Ib/II trial evaluated the efficacy of the <em>CDK4/6</em> inhibitor, abemaciclib, combined with paclitaxel against <em>CDK4/</em><em>6</em>-activated tumors.</div></div><div><h3>Patients and methods</h3><div>Patients with locally advanced or metastatic solid tumors with <em>CDK4/6</em> pathway aberrations were included. Based on phase Ib, the recommended phase II doses were determined as abemaciclib 100 mg twice daily and paclitaxel 70 mg/m² on days 1, 8, and 15, over 4-week-long cycles. The primary endpoint for phase II was the overall response rate (ORR). The secondary endpoints included the clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Tissue-based next-generation sequencing and exploratory circulating tumor DNA analyses were carried out.</div></div><div><h3>Results</h3><div>Between February 2021 and April 2022, 30 patients received abemaciclib/paclitaxel (median follow-up: 15.7 months), and 27 were included in the efficacy analysis. <em>CDK4/6</em> amplification (50%) and <em>CCND1/3</em> amplification (20%) were common activating mutations. The ORR was 7.4%, with two partial responses, and the CBR was 66.7% (18/27 patients). The median OS and PFS were 9.9 months [95% confidence interval (CI) 5.7-14.0 months] and 3.5 months (95% CI 2.6-4.3 months), respectively. Grade 3 adverse events (50%, 21 events) were mainly hematologic. Genetic analysis revealed a ‘poor genetic status’ subgroup characterized by mutations in key signaling pathways (RAS, Wnt, PI3K, and NOTCH) and/or <em>CCNE</em> amplification, correlating with poorer PFS.</div></div><div><h3>Conclusion</h3><div>Abemaciclib and paclitaxel showed moderate clinical benefits for <em>CDK4/</em><em>6</em>-activated tumors. We identified a poor genetic group characterized by bypass signaling pathway activation and/or <em>CCNE</em> amplification, which negatively affected treatment response and survival. Future studies with homogeneous patient groups are required to validate these findings.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104106"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058484","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":"Interobserver consistency and diagnostic challenges in HER2-ultralow breast cancer: a multicenter study","authors":"S. Wu ,&nbsp;J. Shang ,&nbsp;Z. Li ,&nbsp;H. Liu ,&nbsp;X. Xu ,&nbsp;Z. Zhang ,&nbsp;Y. Wang ,&nbsp;M. Zhao ,&nbsp;M. Yue ,&nbsp;J. He ,&nbsp;J. Miao ,&nbsp;Y. Sang ,&nbsp;J. Yan ,&nbsp;W. Pang ,&nbsp;Q. Shao ,&nbsp;Y. Zhang ,&nbsp;M. Zhao ,&nbsp;X. Liu ,&nbsp;P. Wang ,&nbsp;C. Cai ,&nbsp;Y. Liu","doi":"10.1016/j.esmoop.2024.104127","DOIUrl":"10.1016/j.esmoop.2024.104127","url":null,"abstract":"<div><h3>Background</h3><div>Recent advancements in novel antibody–drug conjugates (ADCs) have demonstrated efficacy in patients with human epidermal growth factor receptor 2 (HER2)-ultralow breast cancer (BC), expanding the eligibility for anti-HER2 targeted therapy to include some patients previously categorized as HER2 immunohistochemistry (IHC) 0. This expansion underscores the need for pathologists to accurately differentiate HER2-null and HER2-ultralow.</div></div><div><h3>Materials and methods</h3><div>Thirty-six pathologists from four centers nationwide conducted microscopic visual assessments on HER2 IHC slides from 50 consecutive BC surgical specimens, all previously diagnosed as HER2 IHC 0.</div></div><div><h3>Results</h3><div>The interobserver consistency in differentiating HER2-null from HER2-ultralow, measured by Fleiss κ, was only 0.230—lower than the consistency for combined HER2 IHC 0 cases (Fleiss κ = 0.344) and binary classification (HER2-null versus HER2-non-null; Fleiss κ = 0.292). High agreement for HER2-null versus HER2-ultralow differentiation was achieved in only 4% of cases, while combining them into HER2 IHC 0 raised high agreement cases to 32%, higher than the 18% seen in the binary classification. Consensus among the 36 pathologists aligned with historical scores in 72% of cases; however, when subdividing HER2 IHC 0 into HER2-null and HER2-ultralow, the consistency dropped to 54%.</div></div><div><h3>Conclusions</h3><div>The low consistency among pathologists in distinguishing HER2-null, -ultralow, and 1+ cases may impact patient eligibility for new ADC therapies. To address this challenge, there is a need for improved detection methods, artificial intelligence-assisted quantitative assessments, and larger clinical datasets to refine the definition of HER2-ultralow.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104127"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074154","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":"Tumor-infiltrating lymphocytes in HER2-positive breast cancer: potential impact and challenges","authors":"I. Schlam ,&nbsp;S. Loi ,&nbsp;R. Salgado ,&nbsp;S.M. Swain","doi":"10.1016/j.esmoop.2024.104120","DOIUrl":"10.1016/j.esmoop.2024.104120","url":null,"abstract":"<div><h3>Introduction</h3><div>In this review, we evaluate the role of stromal tumor-infiltrating lymphocytes (sTILs) as a biomarker in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, exploring the prognostic and predictive potential in various treatment settings.</div></div><div><h3>Methods</h3><div>Data from multiple clinical trials in the early and metastatic settings, focusing on TILs’ correlation with pathologic complete response (pCR), progression-free survival (PFS), and overall survival across early and metastatic HER2-positive breast cancer were summarized. This review also discusses TILs’ assessment methods, interobserver variability, and emerging technologies to assess TILs.</div></div><div><h3>Results</h3><div>TILs have been identified as a highly reproducible biomarker that predicts pCR in patients receiving neoadjuvant therapy and serves as a prognostic indicator for long-term outcomes in several breast cancer subtypes, including HER2-positive. Studies indicate that higher TIL levels correlate with better recurrence-free survival rates. Despite these findings, there is no consensus on the optimal TIL threshold for clinical decision making, and further research is required on how to incorporate TILs into routine clinical practice.</div></div><div><h3>Conclusions</h3><div>TILs represent a promising biomarker in HER2-positive breast cancer, particularly in early disease settings. This assessment could guide treatment de-escalation or intensification, tailoring therapies to individual patient profiles. Due to their prognostic importance, TILs can be added to pathology reports. However, further validation in clinical trials is essential for the widespread adoption of TILs in clinical practice.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104120"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002212","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 prognostic and predictive value of the luminal-like subtype in hormone receptor-positive breast cancer: an analysis of the DATA trial","authors":"S.W.M. Lammers ,&nbsp;S.M.E. Geurts ,&nbsp;K.E.P.E. Hermans ,&nbsp;L.F.S. Kooreman ,&nbsp;A.C.P. Swinkels ,&nbsp;C.H. Smorenburg ,&nbsp;M.J.C. van der Sangen ,&nbsp;J.R. Kroep ,&nbsp;A.H. Honkoop ,&nbsp;F.W.P.J. van den Berkmortel ,&nbsp;W.K. de Roos ,&nbsp;S.C. Linn ,&nbsp;A.L.T. Imholz ,&nbsp;I.J.H. Vriens ,&nbsp;V.C.G. Tjan-Heijnen ,&nbsp;Dutch Breast Cancer Research Group (BOOG) for the DATA investigators","doi":"10.1016/j.esmoop.2025.104154","DOIUrl":"10.1016/j.esmoop.2025.104154","url":null,"abstract":"<div><h3>Background</h3><div>This study determines the prognostic value of the luminal-like subtype in patients with hormone receptor-positive breast cancer and explores whether the efficacy of extended anastrozole therapy differs between patients with luminal A-like versus luminal B-like tumours.</div></div><div><h3>Materials and methods</h3><div>The phase III DATA study (NCT00301457) examined the efficacy of 6 versus 3 years of anastrozole in postmenopausal women with early-stage hormone receptor-positive breast cancer who had received 2-3 years of tamoxifen. Patients with available formalin-fixed paraffin-embedded tissue blocks were identified and classified by immunohistochemical luminal-like subtype. Distant recurrence (DR) and breast cancer-specific mortality (BCSM) were compared by luminal-like subtype and treatment arm using competing risk methods.</div></div><div><h3>Results</h3><div>This study included 788 patients: 491 had a luminal A-like tumour and 297 had a luminal B-like tumour. The median follow-up time was 13.1 years. Patients with luminal B-like tumours experienced a higher risk of DR [subdistribution hazard ratio (sHR) 1.44, 95% confidence interval (CI) 1.03-2.01, <em>P</em> = 0.03] and BCSM (sHR 1.68, 95% CI 1.15-2.45, <em>P</em> = 0.008) than patients with luminal A-like tumours. The efficacy of extended anastrozole therapy differed between patients with luminal A-like tumours (DR: sHR 0.51, 95% CI 0.30-0.88, <em>P</em> = 0.02; BCSM: sHR 0.39, 95% CI 0.19-0.82, <em>P</em> = 0.01) and patients with luminal B-like tumours (DR: sHR 2.09, 95% CI 0.96-4.53, <em>P</em> = 0.06; BCSM: sHR 2.36, 95% CI 0.80-7.00, <em>P</em> = 0.12) (<em>P</em>-interaction = 0.03 and <em>P</em>-interaction = 0.06, respectively).</div></div><div><h3>Conclusion</h3><div>In patients with hormone receptor-positive breast cancer, the luminal B-like subtype was associated with a significantly worse prognosis when compared with the luminal A-like subtype. Extended anastrozole therapy halved the risk of DR and BCSM in patients with luminal A-like tumours, whereas no effect was seen in patients with luminal B-like tumours.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104154"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350063","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":"Psychiatric disorders in adolescent and young adult cancer survivors in Korea","authors":"S.-M. Jeong ,&nbsp;D. Kang ,&nbsp;H. Kim ,&nbsp;K.H. Jeon ,&nbsp;H.L. Choi ,&nbsp;H.Y. Park ,&nbsp;S. Kim ,&nbsp;J. Cho ,&nbsp;D.W. Shin","doi":"10.1016/j.esmoop.2024.104101","DOIUrl":"10.1016/j.esmoop.2024.104101","url":null,"abstract":"<div><h3>Background</h3><div>Although adolescent and young adult (AYA) cancer survivors have an increased risk of psychiatric disorders, limited evidence has been suggested. We aimed to determine the risk of psychiatric disorders among AYA cancer survivors.</div></div><div><h3>Materials and methods</h3><div>A retrospective population-based cohort study based on the Korea National Health Insurance Service database was carried out. All men and women aged 15-39 years diagnosed with cancer between 2006 and 2019 (<em>N</em> = 88 965) were included and matched with controls (1 : 4). The prevalence ratios (PRs) of psychiatric disorders were calculated in cancer patients and compared with those in the control group every 6 months before and after cancer diagnosis.</div></div><div><h3>Results</h3><div>The mean age of the participants was 32.2 years and the majority were 30-39 years of age (72.9%). There was no difference in the PRs of psychiatric disorders between AYA cancer patients and the control group before cancer diagnosis, but it increased sharply after cancer diagnosis [PR 2.50, 95% confidence interval (CI) 2.42-2.58 in the first 6 months]. During a median follow-up of 6.5 years, 54 733 participants developed psychiatric disorders. The overall risk of psychiatric disorders among AYA cancer survivors compared with the control group had a sub-distribution hazard ratio of 1.42 (95% CI 1.39-1.45) after considering competing risks.</div></div><div><h3>Conclusions</h3><div>Our study confirmed a 42% increased risk of psychiatric disorders among AYA cancer survivors compared with controls across various cancer types. Our findings suggest that AYA cancer survivors require long-term psychological support following their cancer diagnosis.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104101"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058513","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":"Phase I trial of the combination of the pan-ErbB inhibitor neratinib and mTOR inhibitor everolimus in advanced cancer patients with ErbB family gene alterations","authors":"S.A. Piha-Paul ,&nbsp;C. Tseng ,&nbsp;H.T. Tran ,&nbsp;A. Naing ,&nbsp;E.E. Dumbrava ,&nbsp;D.D. Karp ,&nbsp;J. Rodon ,&nbsp;T.A. Yap ,&nbsp;K.P. Raghav ,&nbsp;S. Damodaran ,&nbsp;X. Le ,&nbsp;P.T. Soliman ,&nbsp;J. Lim ,&nbsp;F. Meric-Bernstam","doi":"10.1016/j.esmoop.2025.104136","DOIUrl":"10.1016/j.esmoop.2025.104136","url":null,"abstract":"<div><h3>Background</h3><div>The ErbB family of receptor tyrosine kinases are key targets for antitumor therapy. Although neratinib, a pan-ErbB kinase inhibitor, is approved in ErbB2-positive breast cancer, drug resistance is common. Preclinical data suggest that combining neratinib with the mTOR inhibitor everolimus may overcome such resistance.</div></div><div><h3>Patients and methods</h3><div>Our trial evaluated this combination’s safety and efficacy in advanced cancers with ErbB alterations. We conducted a phase I dose-escalation trial of neratinib and everolimus. Primary objectives were to assess safety, tolerability, and dose-limiting toxicities (DLTs) and establish the maximum tolerated dose (MTD). Secondary objectives included objective response by RECIST v1.1 and pharmacokinetic analyses.</div></div><div><h3>Results</h3><div>Twenty-two patients (median age 61, median of four prior therapies) with ErbB alterations (mutations 63.6%, amplification 36.3%, or ErbB2-overexpressed by immunohistochemistry 9.1%) were enrolled. Common tumor types included breast (31.8%), colorectal (18.2%), cervical (9.1%), and endometrial (9.1%) cancers. Frequent grade (G) 3 treatment-related adverse events were diarrhea (18.2%), anemia (9.1%), mucositis (9.1%), and acute kidney injury (9.1%). DLTs included G3 mucositis and diarrhea at dose level (DL) 5, and G3 increased creatinine at DL4. The MTD was DL4: neratinib 240 mg with everolimus 7.5 mg. The objective response rate was 19% with partial response in four patients. Stable disease ≥16 weeks was seen in two patients (9.5%), resulting in a clinical benefit rate of 28.6%.</div></div><div><h3>Conclusion</h3><div>Pharmacokinetic data indicated reduced neratinib clearance possibly due to CYP3A4 pathway saturation by everolimus. Combination therapy with neratinib and everolimus has a tolerable safety profile and clinical activity in ErbB-altered patients. ErbB family receptors and the PI3K pathway are commonly implicated in oncogenesis. This clinical study of neratinib and everolimus demonstrated favorable clinical activity and tolerability.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104136"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132656","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":"Outcomes and prognostic indicators in daratumumab-refractory multiple myeloma: a multicenter real-world study of elotuzumab, pomalidomide, and dexamethasone in 247 patients","authors":"E.A. Martino ,&nbsp;S. Palmieri ,&nbsp;M. Galli ,&nbsp;D. Derudas ,&nbsp;R. Mina ,&nbsp;R. Della Pepa ,&nbsp;R. Zambello ,&nbsp;E. Vigna ,&nbsp;A. Bruzzese ,&nbsp;S. Mangiacavalli ,&nbsp;E. Zamagni ,&nbsp;C. Califano ,&nbsp;M. Musso ,&nbsp;C. Conticello ,&nbsp;C. Cerchione ,&nbsp;G. Mele ,&nbsp;N. Di Renzo ,&nbsp;M. Offidani ,&nbsp;G. Tarantini ,&nbsp;G.M. Casaluci ,&nbsp;M. Gentile","doi":"10.1016/j.esmoop.2024.104084","DOIUrl":"10.1016/j.esmoop.2024.104084","url":null,"abstract":"<div><h3>Background</h3><div>Daratumumab-refractory multiple myeloma (Dara-R MM) presents a significant treatment challenge. This study aimed to evaluate the efficacy and survival outcomes of elotuzumab, pomalidomide, and dexamethasone (EloPd) in a large, real-world cohort of patients with Dara-R MM, with particular focus on progression-free survival (PFS) and overall survival (OS).</div></div><div><h3>Materials and methods</h3><div>This retrospective analysis included 247 Dara-R MM patients treated with EloPd. All patients were also refractory to lenalidomide, with 51.4% to a proteasome inhibitor, thus classified as triple-class refractory (TCR). Survival risk-scoring systems for PFS (progression-free risk score-PRS_{<em>DaraR</em>}) and OS (survival risk score-SRS_{<em>DaraR</em>}) were developed to stratify patients based on their risk profiles.</div></div><div><h3>Results</h3><div>The overall response rate was 52.6%, with a median PFS and OS of 6.6 and 17.0 months, respectively. The International Staging System (ISS) stages II and III, low hemoglobin (Hb) levels, the last therapy being daratumumab, and symptomatic relapse were identified as significant independent predictors of shorter PFS in multivariable analysis. In addition to advanced ISS stages, low Hb levels (&lt;10.6 g/dl), symptomatic relapse, and refractory disease exhibited an independent negative impact on OS. Importantly, no significant differences in both PFS and OS were observed between TCR and non-TCR patients. Based on these multivariable analyses, we developed PRS_{<em>DaraR</em>} and SRS_{<em>DaraR</em>} according to the magnitude of the hazard ratio. In PRS_{<em>DaraR</em>}, 10.1% were low-risk, 41.3% intermediate, 43.3% high, and 5.3% very high-risk. The 12-month PFS probabilities were 86.3% (low), 67.6% (intermediate), 52.9% (high), and 31.8% (very high). For SRS_{<em>DaraR</em>}, 6.1% were low-risk, 47.8% intermediate, 19.4% high, and 26.7% very high. The 12-month OS probabilities were 90.9% (low), 75.7% (intermediate), 55.9% (high), and 32.6% (very high).</div></div><div><h3>Conclusions</h3><div>This study supports EloPd as an effective treatment option in Dara-R MM patients, providing valuable disease control and acting as a potential bridge to newer therapies, such as CAR-T and bispecific antibodies.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104084"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946613","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":"HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers☆","authors":"F. Lynce ,&nbsp;O. Martínez-Sáez ,&nbsp;B. Walbaum ,&nbsp;F. Brasó-Maristany ,&nbsp;A.G. Waks ,&nbsp;P. Villagrasa ,&nbsp;G. Villacampa Javierre ,&nbsp;E. Sanfeliu ,&nbsp;P. Galván ,&nbsp;L. Paré ,&nbsp;L.M. Anderson ,&nbsp;C.M. Perou ,&nbsp;J.S. Parker ,&nbsp;A. Vivancos ,&nbsp;M.K. DiLullo ,&nbsp;S. Pernas ,&nbsp;E.P. Winer ,&nbsp;B. Overmoyer ,&nbsp;E.A. Mittendorf ,&nbsp;C. Bueno-Muiño ,&nbsp;S.M. Tolaney","doi":"10.1016/j.esmoop.2024.104100","DOIUrl":"10.1016/j.esmoop.2024.104100","url":null,"abstract":"<div><h3>Background</h3><div>The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC).</div></div><div><h3>Patients and methods</h3><div>HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay’s predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts. Comparative analyses included HER2DX scores, gene signatures, and expression of individual genes between patients with IBC and non-IBC.</div></div><div><h3>Results</h3><div>Notable differences in clinicopathological characteristics included higher pertuzumab and chemotherapy usage and lower axillary burden in patients with IBC compared with non-IBC. In the combined cohort (<em>n</em> = 179), HER2DX pCR score and pertuzumab use were significant predictors of pCR, but not IBC status. The pCR rates in patients treated with trastuzumab-based chemotherapy (including IBC and non-IBC) were 68.9%, 58.5%, and 16.3% in the HER2DX pCR-high, -medium, and -low groups, respectively. Comparative gene expression analysis indicated minor differences between IBC and non-IBC affecting individual <em>HER2</em>, immune, and proliferation genes.</div></div><div><h3>Conclusions</h3><div>The HER2DX pCR score could predict pCR in stage III HER2-positive IBC following treatment with de-escalated neoadjuvant systemic therapy and in stage III HER2-positive non-IBC. Elevated pCR rates in HER2-positive IBC with high HER2DX pCR scores suggest there may be a role for treatment de-escalation in these patients and confirmatory studies are justified.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104100"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002110","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}