Therapeutic Advances in Medical Oncology最新文献

{"title":"Corrigendum to \"Outcomes of patients with refractory upper GI cancers enrolled in phase I trials: a 10-year analysis from the Sarah Cannon Research Institute UK Drug Development Unit\".","authors":"","doi":"10.1177/17588359251334877","DOIUrl":"https://doi.org/10.1177/17588359251334877","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/17588359251318864.].</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251334877"},"PeriodicalIF":4.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038599","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":"ICOS and ICOS ligand: expression patterns and outcomes in oncology patients.","authors":"Mina Nikanjam, Shumei Kato, Daisuke Nishizaki, Donald A Barkauskas, Sarabjot Pabla, Mary K Nesline, Jeffrey M Conroy, Aung Naing, Razelle Kurzrock","doi":"10.1177/17588359251330514","DOIUrl":"https://doi.org/10.1177/17588359251330514","url":null,"abstract":"<p><strong>Background: </strong>Inducible T-cell co-stimulator (ICOS) and its ligand (ICOSL) form a complex, two-faced immune machinery that can lead to both immune stimulation and inhibition.</p><p><strong>Objective: </strong>We explored ICOS transcriptomic expression patterns and their relationship with other checkpoints and with outcomes in patients with advanced/metastatic cancers.</p><p><strong>Design: </strong>This was a retrospective cohort study.</p><p><strong>Methods: </strong>RNA expression for ICOS and other immune checkpoints was quantified by RNA sequencing and stratified by rank values into high (75-100 percentiles) and low (0-24 percentiles). Fischer's exact tests were used for univariate analyses to evaluate independent predictors of ICOS high and logistic regression was used for multivariate analyses. Progression-free survival (PFS) and overall survival (OS) for ICOS high versus not high expression were evaluated using the log-rank test (Kaplan-Meier analysis) and Cox proportional hazards.</p><p><strong>Results: </strong>High ICOS (⩾75 percentile RNA rank) was present in 14% of 514 cancers and independently associated with high PD-1 (<i>p</i> = 0.025), PD-L1 (<i>p</i> < 0.0001), and CTLA-4 RNA expression (<i>p</i> < 0.0001) and with patients not having colorectal cancer (<i>p</i> = 0.0009; multivariate analysis). Patterns of ICOS and ICOSL expression varied between and within tumor types. For 217 patients receiving immune checkpoint inhibitors (ICIs), there were no significant differences in PFS or OS between patients with ICOS high versus not-high expression (multivariate analysis). In 272 immunotherapy-naïve patients, OS was also similar between patients with ICOS high versus not-high expression (<i>p</i> = 0.91).</p><p><strong>Conclusion: </strong>High ICOS expression was not a prognostic marker and did not independently predict outcomes after ICIs. Variable expression of ICOS/ICOSL between tumors and association of high ICOS with high PD-1, PD-L1, and CTLA-4 suggest that individual tumor immunomic analysis may be required for optimized patient selection in clinical trials targeting the ICOS/ICOSL system, especially when given in combination with ICIs.</p><p><strong>Trial registration: </strong>UCSD_PREDICT, NCT02478931.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251330514"},"PeriodicalIF":4.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027140","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":"Navigating second-line therapy in metastatic renal cell carcinoma: a comparative analysis of immune checkpoint inhibitors and tyrosine kinase inhibitors: a study of Turkish Oncology Group Kidney Cancer Consortium.","authors":"Musa Barış Aykan, Hatice Bölek, Emre Yekedüz, Elif Sertesen, Deniz Tural, Cengiz Karaçin, Mehmet Ali Nahit Şendur, Gökhan Uçar, Çağatay Arslan, Selver Işık, Saadet Sim, Özlem Nuray Sever, Bekir Hacıoğlu, Sema Sezgin Göksu, Mustafa Özgüroğlu, Nuri Karadurmuş, Yüksel Ürün","doi":"10.1177/17588359251331540","DOIUrl":"https://doi.org/10.1177/17588359251331540","url":null,"abstract":"<p><strong>Background: </strong>Despite progress in treatment, many metastatic renal cell carcinoma (mRCC) patients still experience progression after first-line tyrosine kinase inhibitor (TKI), necessitating effective second-line options. While guidelines endorse combination therapies, accessibility limitations often restrict therapy to TKI monotherapy.</p><p><strong>Objectives: </strong>Existing decision-making relies on limited evidence, lacking direct comparisons between the leading second-line options (cabozantinib and nivolumab) which surpass everolimus in advanced mRCC. To address this gap, this study compares the efficacy of TKI versus nivolumab in second line while investigating factors influencing outcomes.</p><p><strong>Design: </strong>This was a retrospective cohort study.</p><p><strong>Methods: </strong>Turkish Oncology Group Kidney Cancer Consortium includes more than 1000 mRCC patients from 13 centers in Türkiye. It has the largest national data. We extracted 214 patients treated with a TKI in the first line and nivolumab or TKI in the second line.</p><p><strong>Results: </strong>The median overall survival (OS) and time to treatment failure (TTF) were similar in the TKI-TKI and TKI-immune checkpoint inhibitor (ICI; 41.1 and 44.8 months, <i>p</i> = 0.446 for OS; 27.4 and 29.8 months, <i>p</i> = 0.857 for TTF). The presence of previous nephrectomy for TTF made a significant difference in univariable and multivariable analysis. Bone metastases negatively affected TTF in both univariable and multivariable analyses. In the neutrophil-to-lymphocyte ratio (NLR)-high group, OS and TTF were longer in patients treated with TKI-ICI than in the TKI-TKI. In multivariable analysis, NLR was an independent prognostic factor for OS and TTF to select ICI in the second-line.</p><p><strong>Conclusion: </strong>Our analysis revealed no significant difference in OS between patients receiving ICIs or TKIs as second-line therapy. In the subgroup of patients with elevated NLR, ICI therapy was found to cause no improvement in OS. This finding suggests the potential utility of NLR as a biomarker to guide targeted selection of ICI therapy among patients progressing after first-line TKIs. Furthermore, our study identified other noteworthy prognostic factors influencing outcomes, including the presence of bone or liver metastases, Eastern Cooperative Oncology Group performance status, and International Metastatic Renal Cell Carcinoma Database Consortium risk score.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251331540"},"PeriodicalIF":4.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987727","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 mechanisms of HER2 targeted ADCs are dependent on Rab GTPases.","authors":"Astrid Medhus, Kay Oliver Schink, Ane Sager Longva, Olav Engebraaten, Kristian Berg, Anette Weyergang","doi":"10.1177/17588359251332473","DOIUrl":"https://doi.org/10.1177/17588359251332473","url":null,"abstract":"<p><strong>Introduction: </strong>In the era of personalized cancer therapy, antibody-drug conjugates (ADCs) have become one of the fastest-emerging groups of anticancer drugs. ADCs consist of an antibody coupled to a cytotoxic payload by a chemical linker, designed to be cleaved off intracellularly. Understanding the intracellular trafficking and processing of ADCs is crucial for elucidating their mechanism of action.</p><p><strong>Objective: </strong>This study aimed to compare trastuzumab deruxtecan (T-DXd) to ado-trastuzumab emtansine (T-DM1) with emphasis on Rab GTPase-regulated intracellular trafficking and its impact on ADC efficacy.</p><p><strong>Methods: </strong>The efficacy of T-DXd and T-DM1 was assessed in a panel of HER2-positive cell lines. Correlations between ADC efficacy and the expression of HER2 and Rab GTPases were evaluated. Functional studies, including knockdown (KD), overexpression, and microscopy, were performed to evaluate the impact of Rab GTPases on ADC cytotoxicity.</p><p><strong>Results: </strong>In contrast to T-DM1, T-DXd efficacy was found not to correlate to HER2 expression in a panel of HER2-positive cell lines. However, a correlation to RAB5A expression was found for T-DXd efficacy, although not as strong as for T-DM1. Altering the expression of RAB5 in our model system confirmed RAB5 to have an impact on both T-DXd and T-DM1 cytotoxicity, but more on T-DM1. In addition, RAB4a was found to influence T-DXd sensitivity, but not T-DM1, indicating differences in intracellular processing between T-DXd and T-DM1.</p><p><strong>Conclusion: </strong>The study demonstrates that ADC design significantly influences intracellular trafficking and processing. The linker design, in particular, plays a major role in determining the intracellular fate of an ADC.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251332473"},"PeriodicalIF":4.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052547","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":"Efficacy and safety of radiotherapy to delay second-line systemic therapy in patients with oligoprogressive hepatocellular carcinoma: study protocol of a multicentre, single-arm, phase II trial.","authors":"Haohua Wang, Xiang Zhang, Kunli Zhu, Shumei Jiang, Tianxing Liu, Rui Feng, Xue Dou, Lei Xu, Junyi He, Fang Shi, Jinbo Yue","doi":"10.1177/17588359251334538","DOIUrl":"https://doi.org/10.1177/17588359251334538","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a highly aggressive cancer with a paucity of efficacious treatment options, particularly in advanced stages following first-line systemic therapy (FLST).</p><p><strong>Objectives: </strong>The objective of this trial is to assess the efficacy and safety of radiotherapy as a treatment option to prolong progression-free survival (PFS) and delay the necessity for second-line systemic therapy (SLST) in patients with oligoprogressive HCC following FLST.</p><p><strong>Design: </strong>Multicentre, single-arm, phase II trial.</p><p><strong>Methods and analysis: </strong>This prospective, multicentre, single-arm phase II clinical trial will enrol 36 patients with oligoprogressive advanced HCC following FLST. A comprehensive clinical imaging evaluation will be conducted to confirm the presence of oligoprogressive disease, categorized as metachronous oligoprogression, repeat oligoprogression or induced oligoprogression. Furthermore, patients must have demonstrated stability of the primary HCC for a minimum of 3 months during FLST. Eligible patients will receive radiotherapy for all oligoprogressive lesions with a biologically effective dose (LQ, α/β = 10) of at least 60 Gy while continuing their current FLST until disease progression necessitates SLST. The primary endpoint is PFS, with secondary endpoints including objective remission rate, overall survival (OS), disease control rate, safety and duration of disease remission.</p><p><strong>Ethics: </strong>The final protocol was approved by the Ethics Committee of the Affiliated Cancer Hospital of Shandong First Medical University.</p><p><strong>Discussion: </strong>Given the greater number of options for FLST in advanced HCC, which have demonstrated improvements in PFS and OS, and the limited number and less effective SLST options, this phase II trial aims to evaluate the use of radiotherapy to extend PFS and delay the application of SLST in patients with oligoprogressive HCC after FLST. This approach may preserve SLST options for more aggressive, widespread metastatic disease in the future.</p><p><strong>Trial registration: </strong>This study is registered on ClinicalTrials.gov identifier: NCT06261047.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251334538"},"PeriodicalIF":4.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049551","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 antibody-drug conjugate targeting ROR1, NBE-002, is active in high-grade serous ovarian cancer preclinical models.","authors":"Dongli Liu, Cassandra J Vandenberg, Patrizia Sini, Lorenz Waldmeier, Rosa Baumgartinger, Laura Pisarsky, Georg Petroczi, Gayanie Ratnayake, Clare L Scott, Caroline E Ford","doi":"10.1177/17588359251332471","DOIUrl":"https://doi.org/10.1177/17588359251332471","url":null,"abstract":"<p><strong>Background: </strong>Novel therapeutics are urgently needed for high-grade serous ovarian cancer (HGSOC). We identified the receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a therapeutic target. NBE-002, an antibody-drug conjugate (ADC) consisting of a humanised anti-ROR1 antibody, huXBR1-402, linked to a highly potent anthracycline-derivative (PNU), has activity in ROR1-positive haematologic malignancies.</p><p><strong>Objectives: </strong>This study explored the anti-cancer effects of NBE-002 alone and in combination with standard HGSOC therapies, carboplatin, paclitaxel and olaparib.</p><p><strong>Design: </strong>A ROR1-ADC was tested in cell lines and <i>in vivo</i> models of HGSOC.</p><p><strong>Methods: </strong>Different ROR1-targeting antibodies and payload compositions were constructed and tested <i>in vitro</i>. The dose effect of NBE-002 alone and in combination with carboplatin, paclitaxel or olaparib was analysed in ROR1+ HGSOC cell lines. Growth inhibition and apoptosis were monitored by live cell imaging and combination effects determined. Ten HGSOC PDX models were treated with NBE-002 alone, or in combination with carboplatin or olaparib, over 4 weeks and tumour volume and overall survival evaluated.</p><p><strong>Results: </strong>Synergistic interaction was observed in two out of five HGSOC cell lines treated with NBE-002 and carboplatin (PEO4 and OC023, chemo-resistant), in one out of five treated with NBE-002 and olaparib (PEO1, BRCA2 mutated, HR deficient) and none of five treated with NBE-002 and paclitaxel. In vivo, NBE-002 exhibited activity in PA-1 xenografts and three HGSOC PDX models with high ROR1 expression, platinum sensitivity and homologous recombination DNA repair deficient (HRD). When NBE-002 was combined with carboplatin, activity was observed in 7 of 10 ROR1-expressing PDX models, regardless of platinum or HRD status. The activity was demonstrated in combination with olaparib in both PDX tested, one HRD and one HRD reverted.</p><p><strong>Conclusion: </strong>The ROR1-targeting ADC, NBE-002, has therapeutic potential in HGSOC, with single agent activity observed both <i>in vitro</i> and <i>in vivo</i>. Broader clinical applications were evident when NBE-002 was combined with carboplatin or olaparib.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251332471"},"PeriodicalIF":4.3,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039591","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":"TROPION-Breast05: a randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer.","authors":"Peter Schmid, Mafalda Oliveira, Joyce O'Shaughnessy, Massimo Cristofanilli, Stephanie L Graff, Seock-Ah Im, Sherene Loi, Shigehira Saji, Shusen Wang, David W Cescon, Tina Hovey, Agata Nawrot, Karson Tse, Petra Vukovic, Giuseppe Curigliano","doi":"10.1177/17588359251327992","DOIUrl":"https://doi.org/10.1177/17588359251327992","url":null,"abstract":"<p><strong>Background: </strong>Standard of care (SoC) for patients with advanced triple-negative breast cancer (TNBC) whose tumors express PD-L1 (combined positive score ⩾ 10) is chemotherapy plus anti-PD-(L)1 inhibitors; however, prognosis and survival for most patients is poor. Datopotamab deruxtecan (Dato-DXd), a novel antibody-drug conjugate comprising a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor payload via a plasma-stable, cleavable, tetrapeptide-based linker, has shown preliminary activity as mono or combination therapy in advanced/metastatic TNBC.</p><p><strong>Objectives: </strong>TROPION-Breast05 is an ongoing randomized, open-label, multicenter phase III study. The primary objective is to demonstrate the superiority of Dato-DXd in combination with durvalumab (an anti-PD-L1 antibody) versus SoC treatment in patients with PD-L1-high locally recurrent inoperable or metastatic TNBC.</p><p><strong>Methods and design: </strong>Patients (⩾18 years) will be randomized 1:1 to receive Dato-DXd (6 mg/kg intravenously (IV) every 3 weeks (Q3W)) plus durvalumab (1120 mg IV Q3W) or investigator's choice of chemotherapy (ICC; paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) plus pembrolizumab (200 mg IV Q3W). In selected countries, patients will also be randomized (1:1:1) to a third arm of Dato-DXd monotherapy. The primary study endpoint is progression-free survival (PFS) per blinded independent central review (Dato-DXd plus durvalumab arm vs ICC plus pembrolizumab arm). Overall survival is a key secondary endpoint; other secondary endpoints include PFS (investigator-assessed), objective response rate, duration of response, clinical benefit rate at Week 24 (all assessed in the Dato-DXd plus durvalumab arm vs ICC plus pembrolizumab arm), patient-reported outcomes, and safety.</p><p><strong>Ethics: </strong>The study is approved by independent ethics committees or institutional review boards at each study site. All patients will provide written informed consent.</p><p><strong>Discussion: </strong>TROPION-Breast05 will assess the potential role of Dato-DXd with or without durvalumab in patients with PD-L1-high advanced or metastatic TNBC. The findings of this trial could lead to a new treatment option for these patients.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT06103864 (Date of registration: 27 October 2023).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251327992"},"PeriodicalIF":4.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective analysis of capecitabine maintenance therapy in pancreatic ductal adenocarcinoma.","authors":"Jordan Powell, Alexa F Viniotis, Chase Irwin, Gayle S Jameson, Lana Caldwell, Erkut H Borazanci","doi":"10.1177/17588359251321894","DOIUrl":"https://doi.org/10.1177/17588359251321894","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PC) is an aggressive form of cancer treated with chemotherapy regimens such as leucovorin, 5-fluorouracil (5-FU), irinotecan, oxaliplatin (FOLFIRINOX), and gemcitabine plus albumin-bound paclitaxel (nab-Paclitaxel). Maintenance chemotherapy is increasingly being studied as an option for patients with a prior response to chemotherapy, prolonged stable disease, and those unable to tolerate the toxicities of traditional chemotherapy.</p><p><strong>Objective: </strong>Our retrospective analysis aims to evaluate the effectiveness and tolerability of capecitabine as maintenance therapy in patients with PC.</p><p><strong>Design: </strong>Thirty-three patients treated for PC with capecitabine (an oral formulation of 5-FU) maintenance therapy at our single institution between 8/01/2013 and 9/02/2021 were identified on chart review via the electronic medical record (EMR).</p><p><strong>Methods: </strong>Kaplan-Meier curves were fit to evaluate patient progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>Thirty-three individuals were identified: 21 males and 12 females, with a median age of 69 years. Fifteen of 33 had stage IV PC. Nineteen had progression of disease; 8 completed therapy and transitioned to observation or other treatments; 2 did not tolerate treatment; and 4 were still undergoing treatment. The median PFS was 13.01 months (396.0 days), and the median OS was 28.42 months (865.0 days).</p><p><strong>Conclusion: </strong>Maintenance with capecitabine seems safe and may represent a valuable option in patients with advanced PC controlled using FOLFIRINOX or gemcitabine/nab-Paclitaxel induction treatment.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251321894"},"PeriodicalIF":4.3,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998672","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":"Treatment status, survival and gene expression analysis of large-cell neuroendocrine lung carcinoma: a real-world study in China.","authors":"Fei Qi, Minghang Zhang, Yi Han, Juan Du, Hongjie Yang, Hongmei Zhang, Yong Zhang, Tongmei Zhang","doi":"10.1177/17588359251324900","DOIUrl":"https://doi.org/10.1177/17588359251324900","url":null,"abstract":"<p><strong>Background: </strong>Large-cell neuroendocrine lung carcinoma (LCNEC) is a rare subtype of lung cancer that lacks standard treatment at present.</p><p><strong>Purpose: </strong>This study aimed to investigate the treatment status, failure pattern, survival outcome, and gene expression profile of LCNEC in China.</p><p><strong>Design: </strong>This is a real-world retrospective study combined with transcriptome sequencing of LCNEC tumors.</p><p><strong>Methods: </strong>Patients with newly diagnosed LCNEC at Beijing Chest Hospital from 2015 to 2022 were retrospectively reviewed. Treatment, failure pattern, and survival were analyzed. Transcriptome sequencing of LCNEC and non-small-cell lung cancer was conducted for differentiated expressed genes exploration and enrichment analysis.</p><p><strong>Results: </strong>In all, 151 eligible patients met the criteria: stage I (24.5%), II (9.9%), IIIA (13.9%), and IIIB-IV (51.7%). Median progression-free survival (PFS) and overall survival (OS) were 7.9 and 17.8 months for an entire cohort of patients. For stage I/II and IIIA patients receiving radical operation or chemoradiation, 47 out of 77 cases developed treatment failure with 2-year cumulative systemic/distant failure (SF), locoregional failure (LRF), and overall failure rates of 65.2%, 52.7%, and 30.8%, respectively. Failure incidence increased with stage development. Stage III disease presented with a significantly higher cumulative SF rate (2-year, 57.3% vs 29.7%; <i>p</i> = 0.010) but a similar LRF rate (2-year, 41.5% vs 37.6%, <i>p</i> = 0.369) than stage I/II, achieving favorable SF-free survival and comparable LRF-free survival. Adding adjuvant chemotherapy to surgery reduced distant dissemination which translated into survival benefit (2-year SF, 53.7% vs 41.3%, <i>p</i> = 0.055; 2-year OS, 37.1% vs 79.9%, <i>p</i> < 0.001). For advanced LCNEC, immunochemotherapy and chemotherapy alone achieved PFS of 10.3 and 4.7 months, respectively (<i>p</i> = 0.045). Differential gene expression analysis revealed that antigen presentation/processing, chemokine signaling, CXCR4, and IFN-γ pathways were upregulated in LCNEC, suggesting the vulnerability of LCNEC to immunotherapy. Besides, <i>MMP9, AGT, COL1A2, COL1A1</i>, and <i>CXCL9</i> may play vital roles in the LCNEC pathogenesis.</p><p><strong>Conclusion: </strong>LCNEC is a highly aggressive disease and incorporation of immunotherapy might be an effective treatment option.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251324900"},"PeriodicalIF":4.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055054","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":"Comparative real-world outcomes of stage III melanoma patients treated with talimogene laherparepvec or interleukin 2.","authors":"Markus Reitmajer, Lena Nanz, Nina Müller, Ulrike Leiter, Teresa Amaral, Valentin Aebischer, Lukas Flatz, Andrea Forschner","doi":"10.1177/17588359251324035","DOIUrl":"10.1177/17588359251324035","url":null,"abstract":"<p><strong>Background: </strong>Talimogene laherparepvec (T-VEC) and interleukin-2 (IL-2) are both used in the intralesional treatment of melanoma skin metastases. T-VEC received regulatory approval from the European Medicines Agency and the U.S. Food and Drug Administration in 2015, while IL-2 has been used off-label for this purpose for many years. Despite their use in clinical practice, there is a lack of comparative data on the efficacy and safety of these treatments.</p><p><strong>Objectives: </strong>This retrospective study aimed to compare the efficacy and safety of intralesional T-VEC and IL-2 in non-resectable stage III patients with melanoma treated at a single center between January 2016 and September 2024.</p><p><strong>Methods: </strong>We identified eligible patients using the Central Malignant Melanoma Registry and the local University Hospital Pharmacy database. Overall survival (OS) and progression-free survival (PFS) were calculated. Furthermore, best response rates and occurrence of adverse events (AEs) were compared between the T-VEC and the IL-2 group. Concomitant systemic treatment was allowed.</p><p><strong>Results: </strong>A total of 62 patients were included, with 37 receiving T-VEC and 25 receiving IL-2 as first-line therapy. Ten patients received both therapies subsequently. The median PFS for the cohort was 5.0 months, and the median OS was 34.0 months. No significant differences in PFS (<i>p</i> = 0.790), OS (<i>p</i> = 0.894), or best response rates (<i>p</i> = 0.468) were found between groups. Common AEs included local injection site reactions and fever, with no severe events leading to discontinuation by a physician.</p><p><strong>Conclusion: </strong>No significant differences in PFS, OS, or best response rates were observed between IL-2 and T-VEC treatments. The choice of therapy may be influenced by factors such as availability, physician preference, and patient-specific considerations.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251324035"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765034","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}