Journal of Thoracic Oncology最新文献

{"title":"Rapid Intracranial Response With Tarlatamab in Patients With Untreated Brain Metastases From SCLC-A Real-World Case Series: Case Report.","authors":"Bingnan Zhang, Komal B Shah, Mitchell Parma, Kaiwen Wang, Eric K Singhi, Whitney Lewis, Melvin Rivera, Mehmet Altan, Jenny Pozadzides, Xiuning Le, Natalie Vokes, Frank Fossella, Barbara O'Brien, Chenyang Wang, Martin C Tom, Thomas Beckham, Todd Swanson, Julianna Bronk, Steven H Lin, Maria Franco Vega, Joshua Jacome, Alexa Halliday, Marcelo Negrao, Jianjun Zhang, Don L Gibbons, John V Heymach, Lauren A Byers, Carl M Gay","doi":"10.1016/j.jtho.2025.02.023","DOIUrl":"https://doi.org/10.1016/j.jtho.2025.02.023","url":null,"abstract":"<p><p>SCLC has the highest propensity for brain metastases among all malignancies. Systemic treatment for SCLC, particularly in the setting of brain metastases, is very limited. Tarlatamab, the CD3/delta-like ligand 3 bispecific T-cell engager, has changed the treatment landscape of relapsed SCLC since its Food and Drug Administration approval in May 2024. Patients with treated and stable brain metastases were included in the phase 1 DeLLphi-300 trial and phase 2 DeLLphi-301 trials of tarlatamab. Nevertheless, it remains unknown if tarlatamab is safe and efficacious in the setting of untreated, active or symptomatic brain metastases. Our case series provides, to our knowledge, the first reported evidence of the safety and efficacy of tarlatamab in patients with untreated brain metastases. In our cohort of 10 patients with relapsed SCLC and untreated brain metastases, including those with symptomatic intracranial disease and one with suspected leptomeningeal disease, clinical response or stability was seen in 90% of patients. We present several cases in which rapid, dramatic radiographic responses and clinical improvement were observed in patients with innumerable growing brain metastases (>20 lesions) who would otherwise require whole brain radiation, suggesting that tarlatamab can control intracranial metastases as monotherapy, potentially sparing or deferring the need for brain radiation.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anatomic Lung Resection is Associated with Improved Survival Compared with Wedge Resection for Stage IA (≤2 cm) Non-Small Cell Lung Cancer.","authors":"Christopher W Seder, Shu-Ching Chang, Christopher W Towe, Varun Puri, Justin D Blasberg, Levi Bonnell, Felix G Fernandez, Robert H Habib, Benjamin D Kozower","doi":"10.1016/j.jtho.2025.03.042","DOIUrl":"https://doi.org/10.1016/j.jtho.2025.03.042","url":null,"abstract":"<p><strong>Introduction: </strong>Given the uncertain generalizability of recent clinical trial data, a comparative effectiveness analysis examining the long-term survival of \"real world\" patients may clarify the role of lobectomy and sublobar resection (segmentectomy or wedge resection) in the treatment of early-stage non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>Adult patients undergoing lung resection for clinical stage IA NSCLC (≤2 cm) between 2012 and 2022 were identified from the Society of Thoracic Surgeons General Thoracic Surgery Database. Long-term vital status was determined by linkage to the National Death Index and Centers for Medicare & Medicaid Services inpatient data. The primary endpoint was overall survival (OS); secondary endpoints included lung cancer-specific survival (LCSS). Stabilized inverse probability weighted Cox Regression was used to account for selection bias and derive hazard ratios (HR) with 95% confidence intervals comparing the lobectomy, segmentectomy, and wedge resection cohorts.</p><p><strong>Results: </strong>Overall, 32,340 stage IA NSCLC patients (19,778 lobectomies [OS=71.9% (5-year), 44.8% (10-year)], 4,279 segmentectomies [OS=69.6%, 44.2%], and 8,283 wedge resections [OS=66.3%, 41.4%]) were examined. After risk adjustment, lobectomy was associated with improved OS and LCSS compared to sublobar resection [HR(OS)=0.87(0.83-0.92); HR(LCSS)=0.84(0.73-0.97)]. Both lobectomy [HR(OS)=0.84(0.80-0.88); HR(LCSS)=0.72(0.56-0.93)] and segmentectomy [HR(OS)=0.88(0.81-0.95); HR(LCSS)=0.77(0.66-0.89)] were associated with improved survival compared to wedge resection. No differences in OS or LCSS were observed between lobectomy and segmentectomy.</p><p><strong>Conclusion: </strong>In routine clinical practice, lobectomy and segmentectomy are associated with improved overall and lung cancer-specific survival compared with wedge resection for stage IA NSCLC (≤2 cm). These findings highlight the potential gap between trial efficacy and real-world effectiveness.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cemiplimab Monotherapy for First-Line Treatment of Patients with Advanced NSCLC with PD-L1 Expression ≥50%: 5-Year Outcomes of EMPOWER-Lung 1.","authors":"Saadettin Kilickap, Ana Baramidze, Ahmet Sezer, Mustafa Özgüroğlu, Mahmut Gumus, Igor Bondarenko, Miranda Gogishvili, Marina Nechaeva, Michael Schenker, Irfan Cicin, Ho Gwo Fuang, Yaroslav Kulyaba, Kasimova Zyuhal, Roxana-Ioana Scheusan, Marina Chiara Garassino, Yuntong Li, Cong Zhu, Manika Kaul, Javier Perez, Frank Seebach, Israel Lowy, Jean-Francois Pouliot, Eric Kim, Heather Magnan","doi":"10.1016/j.jtho.2025.03.033","DOIUrl":"https://doi.org/10.1016/j.jtho.2025.03.033","url":null,"abstract":"<p><strong>Introduction: </strong>Earlier results from the phase 3 EMPOWER-Lung 1 trial demonstrated significant survival benefits and a generally acceptable safety profile of first-line cemiplimab monotherapy versus chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) expression in ≥50% of tumor cells and no EGFR, ALK, or ROS1 aberrations. Here, we report the 5-year outcomes.</p><p><strong>Methods: </strong>Patients were randomized 1:1 to cemiplimab 350 mg intravenous every 3 weeks for 2 years or investigator's choice of chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS).</p><p><strong>Results: </strong>A total of 712 patients were randomized to cemiplimab (n = 357) or chemotherapy (n = 355). Median duration of follow-up was 59.6 months (interquartile range: 55.1-66.7 months) at the data cutoff (January 16, 2024). In patients with verified PD-L1 ≥50% (n = 565), median OS was 26.1 months for cemiplimab vs. 13.3 months for chemotherapy (hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.48-0.72); median PFS was 8.1 months versus 5.3 months (HR 0.50, 95% CI: 0.41-0.61); the objective response rate was 46.5% versus 20.6%. The 5-year OS probability was 29.0% for cemiplimab and 15.0% for chemotherapy. Improved survival outcomes were observed with both squamous and non-squamous histology, and increasing activity of cemiplimab was correlated with higher PD-L1 expression, with the highest PD-L1 expression having the best outcome. The safety profile remains consistent with previous results. Grade ≥3 treatment-related adverse events occurred in 18.3% of patients for cemiplimab and 39.9% for chemotherapy.</p><p><strong>Conclusions: </strong>At 5-year follow-up, first-line cemiplimab monotherapy continued to show durable clinical benefits versus chemotherapy in patients with advanced NSCLC with PD-L1 ≥50%. Patients with PD-L1 ≥90% derived the largest clinical benefits.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota in Advanced NSCLC Receiving Chemoimmunotherapy: An Ancillary Biomarker Study From the Phase III Trial JCOG2007 (NIPPON).","authors":"Taiki Hakozaki, Kentaro Tanaka, Yoshimasa Shiraishi, Yuta Sekino, Noriko Mitome, Yusuke Okuma, Tomoiki Aiba, Takahiro Utsumi, Junko Tanizaki, Koichi Azuma, Satoshi Hara, Ryo Morita, Seiji Niho, Toshihide Yokoyama, Ryo Toyozawa, Hidehito Horinouchi, Isamu Okamoto, Yukio Hosomi, Yuichiro Ohe","doi":"10.1016/j.jtho.2025.02.026","DOIUrl":"10.1016/j.jtho.2025.02.026","url":null,"abstract":"<p><strong>Introduction: </strong>Immunotherapy has transformed the treatment for NSCLC. Nevertheless, reliable biomarkers for treatment selection remain scarce. Gut microbiota has emerged as a potential biomarker, but its role in chemoimmunotherapy for NSCLC is unclear.</p><p><strong>Methods: </strong>The phase III trial (JCOG2007, NIPPON) compared pembrolizumab plus platinum doublet chemotherapy (PC) with nivolumab and ipilimumab plus platinum doublet chemotherapy (NIC) in treatment-naive patients with advanced NSCLC without driver gene alterations. As an ancillary biomarker study, 270 patients with baseline fecal samples were analyzed for gut microbiota composition from 295 patients enrolled. 16S ribosomal DNA sequencing was performed for the diversity and differential abundance analysis.</p><p><strong>Results: </strong>The beta diversity analysis of the overall cohort (n = 270) revealed distinct microbial structures between the subpopulations defined by whether overall survival (OS) exceeds 12 or 18 months. Subsequent linear discriminant analysis effect size analysis identified specific bacterial genera that differed between the subpopulations, with Fusicatenibacter, Butyricicoccus, and Blautia being enriched in patients with longer OS. Regarding adverse events (AEs), lower microbial alpha diversity and the presence of certain taxa were linked to a higher risk of serious (≥grade 4) AEs. In addition, favorable genera, including Fusicatenibacter and Butyricicoccus, were associated with a lower risk of serious AEs. Last, regimen-specific analysis demonstrated that higher abundance of Fusicatenibacter and Butyricicoccus was linked to better OS in the NIC arm compared with that in the CP arm (hazard ratio for OS = 0.56 and 0.52, respectively). Conversely, the higher abundance of Prevotellaceae NK3B31 was associated with higher mortality risk in the NIC arm (hazard ratio for OS = 2.33).</p><p><strong>Conclusions: </strong>Gut microbiota may serve as a biomarker for chemoimmunotherapy in advanced NSCLC. Differences in microbial diversity and specific bacterial genera were associated with prognosis and serious AEs, with potential regimen-specific effects. These findings support integrating gut microbiota profiling into clinical practice to optimize first-line treatment strategies.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective depletion of CCR8+Treg cells enhances anti-tumor immunity of cytotoxic T cells in lung cancer via dendritic cells.","authors":"Peixin Chen, Haowei Wang, Zhuoran Tang, Jinpeng Shi, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou","doi":"10.1016/j.jtho.2025.02.029","DOIUrl":"https://doi.org/10.1016/j.jtho.2025.02.029","url":null,"abstract":"<p><p>Accumulation of regulatory T (Treg) cells, an immunosuppressive population, limits the efficacy of immunotherapy in non-small cell lung cancer (NSCLC). C-C Motif Chemokine Receptor 8 (CCR8) is selectively expressed in tumor-infiltrating Treg cells and, thus considered an ideal target. Across four NSCLC-bearing mice models, the combination of CCR8 antibody and programmed cell death protein-1 (PD1) inhibitor significantly reduced tumor growth without obvious mouse body weight drops and systemic cytokine storm. The single-cell RNA and T-cell receptor sequencing analysis demonstrated that anti-CCR8 therapy synergizes with PD1 blockade by remodeling the tumor microenvironment and disrupting CCR8+Treg - CCL5+ dendritic cells (DC) interaction. Mechanistically, therapeutic depletion of CCR8+Treg cells combined with PD1 inhibitor extremely increased interleukin-12 secretion by the JAK-STAT pathway activation on CCL5+ DCs, thereby promoting cytotoxic activity of CD8+ T cells. The therapeutic potential of the CCR8 antibody LM-108 in combination with immunotherapy was observed in clinical patients with advanced NSCLC. Overall, CCR8 expression on tumor-infiltrating Treg cells is correlated with immunosuppressive function on DCs and CD8+ T cells, thus impeding anti-tumor immunity.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"10.1016/S1556-0864(25)00039-5","DOIUrl":"10.1016/S1556-0864(25)00039-5","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 3","pages":"Pages A11-A12"},"PeriodicalIF":21.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"40P: Metformin plus/minus cyclic fasting mimicking diet to improve the efficacy of first-line chemo-immunotherapy in advanced LKB1-inactive NSCLC: Results of the phase II trial FAME","authors":"M. Occhipinti ,&nbsp;M. Brambilla ,&nbsp;G. Di Liberti ,&nbsp;C. Proto ,&nbsp;A. Prelaj ,&nbsp;T. Beninato ,&nbsp;M.C. Garassino ,&nbsp;P. Ambrosini ,&nbsp;S. Manglaviti ,&nbsp;L. Mazzeo ,&nbsp;C. Vernieri ,&nbsp;A. Fabbri ,&nbsp;E. Tamborini ,&nbsp;F. Galli ,&nbsp;D. Signorelli ,&nbsp;M.P. Di Palma ,&nbsp;S. De Giorgi ,&nbsp;F.G.M. De Braud ,&nbsp;G. Lo Russo ,&nbsp;M. Ganzinelli","doi":"10.1016/S1556-0864(25)00235-7","DOIUrl":"10.1016/S1556-0864(25)00235-7","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 3","pages":"Pages S36-S37"},"PeriodicalIF":21.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"38P: Two years of follow-up data of a phase II clinical trial of atezolizumab with bevacizumab for patients with PD-L1 high expression non-squamous non-small cell lung cancer (WJOG10718L/@ Be Study)","authors":"T. Seto ,&nbsp;M. Shimokawa ,&nbsp;R. Toyozawa ,&nbsp;S. Sugawara ,&nbsp;H. Hayashi ,&nbsp;H. Murakami ,&nbsp;T. Kato ,&nbsp;S. Niho ,&nbsp;M. Oki ,&nbsp;H. Yoshioka ,&nbsp;H. Daga ,&nbsp;K. Azuma ,&nbsp;S. Miura ,&nbsp;K. Nishino ,&nbsp;M. Satouchi ,&nbsp;I. Okamoto ,&nbsp;N. Yamamoto","doi":"10.1016/S1556-0864(25)00233-3","DOIUrl":"10.1016/S1556-0864(25)00233-3","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 3","pages":"Pages S34-S35"},"PeriodicalIF":21.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"45P: Extended follow-up confirmed real-world efficacy and safety of cemiplimab monotherapy in advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression","authors":"S. Masini ,&nbsp;R. Alvarez Cabellos ,&nbsp;I. De Elejoste Echebarria ,&nbsp;M. Martinez Kareaga ,&nbsp;M. Antonanzas Basa ,&nbsp;M.C. Escoin Perez ,&nbsp;F. Navarro ,&nbsp;C. Traseira Puchol ,&nbsp;L. Cabezon Gutierrez ,&nbsp;S. Falagán Martínez ,&nbsp;C. Garcia Benito ,&nbsp;L. Masfarre Pinto ,&nbsp;C. Avila Andrade ,&nbsp;S. Sequero ,&nbsp;J. Mosquera Martinez ,&nbsp;E. Garcia Lorenzo ,&nbsp;A. Azkárate Martínez ,&nbsp;L. Paz-Ares ,&nbsp;J. Zugazagoitia ,&nbsp;J. Baena Espinar","doi":"10.1016/S1556-0864(25)00240-0","DOIUrl":"10.1016/S1556-0864(25)00240-0","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 3","pages":"Pages S39-S40"},"PeriodicalIF":21.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"46P: Comparison of camrelizumab, pembrolizumab, tislelizumab, and sintilimab as first-line treatment in patients with non-small cell lung cancer: A retrospective study","authors":"S. Yu,&nbsp;Y. Xiaoqi","doi":"10.1016/S1556-0864(25)00241-2","DOIUrl":"10.1016/S1556-0864(25)00241-2","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 3","pages":"Page S40"},"PeriodicalIF":21.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}