Lung Cancer最新文献

{"title":"Treatment patterns and outcomes in KRASG12C‐positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study","authors":"Samir H. Barghout ,&nbsp;Luna Jia Zhan ,&nbsp;Starvroula Raptis ,&nbsp;Faisal Al-Agha ,&nbsp;Niki Esfahanian ,&nbsp;Aimee Popovacki ,&nbsp;Goulnar Kasymjanova ,&nbsp;Francis Proulx-Rocray ,&nbsp;Sze Wah Samuel Chan ,&nbsp;Matthew Richardson ,&nbsp;M. Catherine Brown ,&nbsp;Devalben Patel ,&nbsp;Michelle Liane Dean ,&nbsp;Vishal Navani ,&nbsp;Erica Moore ,&nbsp;Lane Carvery ,&nbsp;Elizabeth Yan ,&nbsp;Daniel Goldshtein ,&nbsp;Jasmine Cleary-Gosine ,&nbsp;Amanda JW Gibson ,&nbsp;Stephanie Snow","doi":"10.1016/j.lungcan.2024.107898","DOIUrl":"10.1016/j.lungcan.2024.107898","url":null,"abstract":"<div><h3>Objectives</h3><p><em>KRAS</em> mutations, particularly <em>KRAS^G12C</em>, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRAS^G12C-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with <em>KRAS^G12C</em>-positive advanced NSCLC receiving systemic therapy post-ICI treatment.</p></div><div><h3>Methods</h3><p>From the CAnadian CAncers With Rare Molecular Alterations-Basket Real-world Observational Study (CARMA-BROS), a cohort of 102 patients with <em>KRAS^G12C</em>-positive advanced NSCLC across 9 Canadian centers diagnosed between 2015 and 2021 was analyzed. Clinico-demographic and treatment data were obtained from electronic health records. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models.</p></div><div><h3>Results</h3><p>The patients (median age 66 years; 58 % female; 99 % current/former tobacco exposure; 59 % PD-L1 ≥ 50 %), exhibited heterogeneous treatment patterns post-ICI. Most patients received ICIs as a first-line therapy, with varying subsequent lines including chemotherapy and targeted therapy. In patients receiving systemic therapy post-ICI, median overall survival was 12.6 months, and real-world progression-free survival was 4.7 months. KRAS^G12C-selective targeted therapy post-ICI (n = 20) showed longer real-world progression-free survival compared to single-agent chemotherapy (aHR = 0.39, <em>p</em> = 0.012).</p></div><div><h3>Conclusion</h3><p>This study contributes valuable real-world data on <em>KRAS^G12C</em>-positive advanced NSCLC post-ICI treatment. The absence of a standard treatment sequencing post-ICI underscores the need for further investigation and consensus-building in the evolving landscape of KRAS^G12C-targeted therapies.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107898"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of prognosis in lung cancer using machine learning with inter-institutional generalizability: A multicenter cohort study (WJOG15121L: REAL-WIND)","authors":"Daichi Fujimoto ,&nbsp;Hidetoshi Hayashi ,&nbsp;Kenta Murotani ,&nbsp;Yukihiro Toi ,&nbsp;Toshihide Yokoyama ,&nbsp;Terufumi Kato ,&nbsp;Teppei Yamaguchi ,&nbsp;Kaoru Tanaka ,&nbsp;Satoru Miura ,&nbsp;Motohiro Tamiya ,&nbsp;Motoko Tachihara ,&nbsp;Takehito Shukuya ,&nbsp;Yuko Tsuchiya-Kawano ,&nbsp;Yuki Sato ,&nbsp;Satoshi Ikeda ,&nbsp;Shinya Sakata ,&nbsp;Takeshi Masuda ,&nbsp;Shinnosuke Takemoto ,&nbsp;Kohei Otsubo ,&nbsp;Ryota Shibaki ,&nbsp;Nobuyuki Yamamoto","doi":"10.1016/j.lungcan.2024.107896","DOIUrl":"10.1016/j.lungcan.2024.107896","url":null,"abstract":"<div><h3>Objectives</h3><p>Predicting the prognosis of lung cancer is crucial for providing optimal medical care. However, a method to accurately predict the overall prognosis in patients with stage IV lung cancer, even with the use of machine learning, has not been established. Moreover, the inter-institutional generalizability of such algorithms remains unexplored. This study aimed to establish machine learning-based algorithms with inter-institutional generalizability to predict prognosis.</p></div><div><h3>Materials and Methods</h3><p>This multicenter, retrospective, hospital-based cohort study included consecutive patients with stage IV lung cancer who were randomly categorized into the training and independent test cohorts with a 2:1 ratio, respectively. The primary metric to assess algorithm performance was the area under the receiver operating characteristic curve in the independent test cohort. To assess the inter-institutional generalizability of the algorithms, we investigated their ability to predict patient outcomes in the remaining facility after being trained using data from 15 other facilities.</p></div><div><h3>Results</h3><p>Overall, 6,751 patients (median age, 70 years) were enrolled, and 1,515 (22 %) showed mutated epidermal growth factor receptor expression. The median overall survival was 16.6 (95 % confidence interval, 15.9–17.5) months. Algorithm performance metrics in the test cohort showed that the areas under the curves were 0.90 (95 % confidence interval, 0.88–0.91), 0.85 (0.84–0.87), 0.83 (0.81–0.85), and 0.85 (0.82–0.87) at 180, 360, 720, and 1,080 predicted survival days, respectively. The performance test of 16 algorithms for investigating inter-institutional generalizability showed median areas under the curves of 0.87 (range, 0.84–0.92), 0.84 (0.78–0.88), 0.84 (0.76–0.89), and 0.84 (0.75–0.90) at 180, 360, 720, and 1,080 days, respectively.</p></div><div><h3>Conclusion</h3><p>This study developed machine learning algorithms that could accurately predict the prognosis in patients with stage IV lung cancer with high inter-institutional generalizability. This can enhance the accuracy of prognosis prediction and support informed and shared decision-making in clinical settings.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107896"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The next-generation KRAS inhibitors…What comes after sotorasib and adagrasib?","authors":"Yuko Oya ,&nbsp;Kazuyoshi Imaizumi ,&nbsp;Tetsuya Mitsudomi","doi":"10.1016/j.lungcan.2024.107886","DOIUrl":"10.1016/j.lungcan.2024.107886","url":null,"abstract":"<div><p>The Kirsten rat sarcoma viral oncogene homolog (<em>KRAS</em>) is one of the first driver oncogenes identified in human cancer in the early 1980s. However, it has been deemed ’undruggable’ for nearly four decades until the discovery of KRAS G12C covalent inhibitors, which marked a pivotal breakthrough. Currently, sotorasib and adagrasib have been approved by the US FDA to treat patients with non-small cell lung cancer (NSCLC) harboring <em>KRAS</em> G12C mutation. However, their efficacy is somewhat limited compared to that of other targeted therapies owing to intrinsic resistance or early acquisition of resistance. While G12C is the predominant subtype of <em>KRAS</em> mutations in NSCLC, G12D/V is prevalent in colorectal and pancreatic cancers. These facts have spurred active research to develop more potent KRAS G12C inhibitors as well as inhibitors targeting non-G12C <em>KRAS</em> mutations. Novel approaches, such as molecular shielding or targeted protein degradation, are also under development. Combining KRAS inhibitors with inhibitors of the receptor-tyrosine kinase-RAS-mitogen-activated protein kinase (MAPK) pathway is underway to counteract redundant feedback mechanisms. Additionally, immunological approaches utilizing T-cell receptor (TCR)-engineered T cell therapy or vaccines, and Hapimmune antibodies are ongoing. This review delineates the recent advancements in KRAS inhibitor development in the post-sotorasib/adagrasib era, with a focus on NSCLC.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107886"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NGS and FISH for MET amplification detection in EGFR TKI resistant non-small cell lung cancer (NSCLC) patients: A prospective, multicenter study in China","authors":"Qian Zheng ,&nbsp;Xue Lin ,&nbsp;Wenli Qi ,&nbsp;Jun Yin ,&nbsp;Juan Li ,&nbsp;Ye Wang ,&nbsp;Weiya Wang ,&nbsp;Weimin Li ,&nbsp;Zongan Liang","doi":"10.1016/j.lungcan.2024.107897","DOIUrl":"10.1016/j.lungcan.2024.107897","url":null,"abstract":"<div><h3>Objectives</h3><p>Comprehensive data using Next-Generation Sequence (NGS) and fluorescence in situ hybridization (FISH) for detecting <em>MET</em> amplification is limited in Chinese patients, we evaluating NGS performance both in tissue and plasma samples using FISH as reference. We also sought to find optimal thresholds value for NGS in detecting <em>MET</em> amplification via bioinformatics methods.</p></div><div><h3>Method</h3><p>Patients progressed after 1st-, 2nd-, or 3rd-generation (G) EGFR-TKIs were enrolled. Tissue biopsy samples were performed for <em>MET</em> amplification detection via both NGS and FISH. Paired plasma samples were collected for <em>MET</em> amplification detection by NGS. The sensitivity, specificity and agreement were analyzed between NGS and FISH.</p></div><div><h3>Results</h3><p>116 eligible patients were analyzed. 44 patients were male. 82 patients were after 3rd generation EGFR-TKI. <em>MET</em> amplification was detected in 43 (37.1 %) patients by FISH, including 19 (16.4 %) polysomy and 24 (20.7 %) focal amplification. The positive rate of <em>MET</em> amplification in post 3rd generation EGFR-TKI and post 1st/2ndgeneration EGFR-TKI resistant patients was 42.7 % (35/82), and 23.5 % (8/34).</p><p>The sensitivity, specificity and agreement of detecting <em>MET</em> amplification by NGS in tissue were 39.5 % (17/43), 98.6 % (72/73) and 76.7 % (89/116), respectively, 66.7 % (16/24), 98.6 % (72/73) and 90.7 % (88/97) for focal <em>MET</em> amplification in tissue and 29.2 % (7/24), 94.5 % (69/73), 78.4 % (76/97) for focal amplification in plasma. Results were shown in the table below.</p></div><div><h3>Conclusion</h3><p>NGS is an alternative method for <em>MET</em> focal amplification detection in tissue. While the sensitivity of NGS testing in plasma needs further improvement to maximize identification of patients with potential benefit from dual-targeted therapy.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107897"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment sequences in EGFR mutant advanced NSCLC","authors":"M. Wespiser,&nbsp;A. Swalduz,&nbsp;M. Pérol","doi":"10.1016/j.lungcan.2024.107895","DOIUrl":"10.1016/j.lungcan.2024.107895","url":null,"abstract":"<div><p>Common <em>EGFR</em> gene mutations (<em>exon 19 deletion</em> and <em>L858R in exon 21</em>) are the most frequent cause of actionable genomic alterations in non-small cell lung cancer (NSCLC) patients. The introduction of EGFR tyrosine kinase inhibitors (TKIs) as 1st-line treatment of advanced stages of the disease has changed the natural history of the disease and extended survival rates, establishing third generation TKIs as a new standard of frontline treatment. Nonetheless, the prolongation of overall survival remains modest, as multiple escape pathways and tumor increasing heterogeneity inevitably develop over time. Several strategies are currently developed to improve these patients’ outcome: prevent the emergence of resistance mechanisms by therapeutic combinations introduced from the first line, act on the residual disease at the time of maximum response to 1st line treatment, develop therapeutic strategies at the time of acquired resistance to TKIs, either dependent on the resistance mechanisms, or agnostic of the resistance pathways. Recent advancements in treatment combinations have shown promising results in prolonging progression-free survival, but often at the cost of more severe side effects in comparison with the current standard of care. These emerging new treatment options open up possibilities for diverse therapeutic sequences in the management of advanced NSCLC depending on common <em>EGFR</em> mutations. The impact on the disease natural history, the patients’ survival and quality of life is not yet fully understood. In this review, we propose an overview of published and forthcoming advances, and a management algorithm considering the different first-line options, integrating the clinical and biological parameters that are critical to clinicians’ decision-making process.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107895"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016950022400429X/pdfft?md5=6b6885c314e529e878663099a5157946&pid=1-s2.0-S016950022400429X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759606","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":"Trajectory of PD-L1 expression in a patient underwent neoadjuvant chemo-immunotherapy for resectable NSCLC","authors":"Filippo Tommaso Gallina ,&nbsp;Vittoria Balzano ,&nbsp;Nicla Porciello ,&nbsp;Riccardo Tajè ,&nbsp;Daniele Forcella ,&nbsp;Enrico Melis ,&nbsp;Fabiana Letizia Cecere ,&nbsp;Francesca Fusco ,&nbsp;Simonetta Buglioni ,&nbsp;Paolo Visca ,&nbsp;Paola Nisticò ,&nbsp;Federico Cappuzzo ,&nbsp;Jonathan Spicer","doi":"10.1016/j.lungcan.2024.107900","DOIUrl":"10.1016/j.lungcan.2024.107900","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"194 ","pages":"Article 107900"},"PeriodicalIF":4.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1000 Robotic-assisted lobectomies for primary lung cancer: 16 years single center experience","authors":"Monica Casiraghi ,&nbsp;Andrea Cara ,&nbsp;Antonio Mazzella ,&nbsp;Lara Girelli ,&nbsp;Giorgio Lo Iacono ,&nbsp;Clarissa Uslenghi ,&nbsp;Giovanni Caffarena ,&nbsp;Riccardo Orlandi ,&nbsp;Luca Bertolaccini ,&nbsp;Patrick Maisonneuve ,&nbsp;Lorenzo Spaggiari","doi":"10.1016/j.lungcan.2024.107903","DOIUrl":"10.1016/j.lungcan.2024.107903","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed at describing our high-volume single center experience in robotic-assisted thoracic surgery (RATS) to evaluate short outcome and feasibility of the technique, the adequacy of oncological results, and the learning curve.</p></div><div><h3>Methods</h3><p>We retrospectively analyzed data from 1000 consecutive patients who underwent lobectomy and systematic lymphadenectomy for primary lung cancer using RATS approach between May 2007 and May 2023.</p></div><div><h3>Results</h3><p>Nine-hundred ninety-seven patients (99.7 %) underwent lobectomy, whereas 3 (0.03 %) patients bilobectomy. Conversion rate to open surgery was 3.7 %. Minor complications occurred in 213 (21.3 %) patients, major complications in 29 patients (2.9 %). The 30-day and 90-day operative mortality was 0 % and 0.1 %, respectively. The median number of N1 + N2 stations resected was 5 (range 0–9), with a median number of 17 of N1 + N2 lymph nodes resected (range 0–55). The oncological outcome was evaluated only on the subgroup of patients (n = 895) with non-small cell lung cancer. Pathological lymph node upstaging from cN0 to pN1/pN2 was evident in 147 patients (17.3 %): 9 % from cN0 to pN1 and 7.1 % from cN0 to pN2. With a median follow-up of 3.9, 5-year OS and DFS were respectively 89.3 % and 83.6 % for stage I, 74 % and 66.5 % for stage II, and 61 % and 36.4 % for stage IIIA.</p></div><div><h3>Conclusions</h3><p>Better vision and excellent instrument maneuverability of the robotic surgical system allowed excellent results in terms of early, adequate oncological outcome comparable to open surgery literature data, and acceptable learning curve.</p></div><div><h3>Ultramini abstract</h3><p>1000 consecutive patients who underwent lobectomy and systematic lymphadenectomy for primary lung cancer using RATS approach have been analyzed with the aim to describe our high-volume single center experience, and to evaluate short outcome and feasibility of the technique, the adequacy of oncological results, and the learning curve.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107903"},"PeriodicalIF":4.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A predictive model for prognostic risk stratification of early-stage NSCLC based on clinicopathological and miRNA panel","authors":"Lisha Ying ,&nbsp;Tingting Lu ,&nbsp;Yiping Tian ,&nbsp;Hui Guo ,&nbsp;Conghui Wu ,&nbsp;Chen Xu ,&nbsp;Jiaoyue Jin ,&nbsp;Rui Zhu ,&nbsp;Pan Liu ,&nbsp;Ying Yang ,&nbsp;Chaodan Yang ,&nbsp;Wenyu Ding ,&nbsp;Chenyang Xu ,&nbsp;Minran Huang ,&nbsp;Zhengxiao Ma ,&nbsp;Yuting Zhang ,&nbsp;Yue Zhuo ,&nbsp;Ruiyang Zou ,&nbsp;Dan Su","doi":"10.1016/j.lungcan.2024.107902","DOIUrl":"10.1016/j.lungcan.2024.107902","url":null,"abstract":"<div><h3>Objective</h3><p>The 5-year survival rate of early-stage non-small cell lung cancer (NSCLC) is still not optimistic. We aimed to construct prognostic tools using clinicopathological (CP) and serum 8-miRNA panel to predict the risk of overall survival (OS) in early-stage NSCLC.</p></div><div><h3>Materials and methods</h3><p>A total of 799 patients with early-stage NSCLC, treated between April 2008 and September 2019, were included in this study. A sub-group of patients with serum samples, 280, were analyzed for miRNA profiling. The primary endpoint of the study was OS. The CP panel for prognosis was developed using multivariate and forward stepwise selection analyses. The serum 8-miRNA panel was developed using the miRNAs that were significant for prognosis, screened using real-time quantitative PCR (qPCR) followed by differential, univariate and Cox regression analyses. The combined model was developed using CP panel and serum 8-miRNA panel. The predictive performance of the panels and the combined model was evaluated using the area under curve (AUC) values of receiver operating characteristics (ROC) curves and Kaplan-Meier survival analysis.</p></div><div><h3>Result</h3><p>The prognostic panels and the combined model (comprising CP panel and serum 8-miRNA panel) was used to classify the patients into high-risk and low-risk groups. The OS rates of these two groups were significantly different (<em>P</em>&lt;0.05). The two panels had higher AUC than the two guidelines, and the combined model had the highest AUC. The AUC of the combined model (AUC=0.788; 95 %CI 0.706–0.871) was better than that of the National Comprehensive Cancer Network (NCCN) guideline (AUC=0.601; 95 %CI 0.505–0.697) and Chinese Society of Clinical Oncology (CSCO) guideline (AUC=0.614; 95 %CI 0.520–0.708).</p></div><div><h3>Conclusion</h3><p>The combined model based on CP panel and serum 8-miRNA panel allows better prognostic risk stratification of patients with early-stage NSCLC to predict risk of OS.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107902"},"PeriodicalIF":4.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Befotertinib for patients with pretreated EGFR T790M mutated locally advanced or metastatic NSCLC: Final overall survival results from a phase 2 trial","authors":"Shun Lu ,&nbsp;Yiping Zhang ,&nbsp;Guojun Zhang ,&nbsp;Jianying Zhou ,&nbsp;Shundong Cang ,&nbsp;Ying Cheng ,&nbsp;Gang Wu ,&nbsp;Peiguo Cao ,&nbsp;Dongqing Lv ,&nbsp;Hong Jian ,&nbsp;Xiangming Jin ,&nbsp;Chengshui Chen ,&nbsp;Panwen Tian ,&nbsp;Kai Wang ,&nbsp;Guanming Jiang ,&nbsp;Gongyan Chen ,&nbsp;Qun Chen ,&nbsp;Hui Zhao ,&nbsp;Cuimin Ding ,&nbsp;Renhua Guo ,&nbsp;Zhilin Shen","doi":"10.1016/j.lungcan.2024.107901","DOIUrl":"10.1016/j.lungcan.2024.107901","url":null,"abstract":"<div><h3>Background</h3><p>In the initial analysis of a pivotal phase 2 single-arm study (NCT03861156), befotertinib (D-0316) showed clinical benefit with a manageable safety profile in pretreated patients with EGFR T790M mutated non-small cell lung cancer (NSCLC), including those with brain metastases.</p></div><div><h3>Methods</h3><p>Eligible patients received oral befotertinib of 50 mg (cohort A) or 75–100 mg (cohort B) once daily until disease progression, withdrawal of informed consent, or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee. OS and safety were secondary endpoints. Herein, we present the final OS and safety data.</p></div><div><h3>Results</h3><p>A total of 176 patients in cohort A and 290 patients in cohort B were finally enrolled. At data cutoff (May 31, 2023), the median duration of follow-up was 47.9 months (95 % CI: 47.1–48.3) in cohort A and 36.7 months (35.9–37.9) in cohort B. The median OS was 23.9 months (95 % CI: 21.1–27.2) in cohort A and 31.5 months (26.8–35.3) in cohort B. The median OS for patients with and without brain metastasis in cohort A was 18.6 months (95 % CI: 14.9–26.3) and 26.4 months (95 % CI: 23.0–29.0), respectively. In cohort B, these data was 23.0 months (95 % CI: 18.6–29.1) and 35.5 months (95 % CI: 29.3–NE), respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1 % in the cohort A and 50.3 % in the cohort B, and 22.2 % and 31.7 % were related to the study drug.</p></div><div><h3>Conclusion</h3><p>Befotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107901"},"PeriodicalIF":4.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141844924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asbestos Surveillance Program Aachen (ASPA): Cancer mortality among asbestos exposed power industry workers","authors":"Nelly Otte ,&nbsp;Ellen Fraune ,&nbsp;Yildiz Cetiner ,&nbsp;Michael K. Felten ,&nbsp;Timm Dirrichs ,&nbsp;Julia Krabbe ,&nbsp;Thomas Kraus","doi":"10.1016/j.lungcan.2024.107899","DOIUrl":"10.1016/j.lungcan.2024.107899","url":null,"abstract":"<div><h3>Background</h3><p>The time between initial asbestos exposure and asbestos-related disease can span several decades. The Asbestos Surveillance Program aims to detect early asbestos-related diseases in a cohort of 8,565 power industry workers formerly exposed to asbestos.</p></div><div><h3>Research question</h3><p>How does asbestos exposure patterns affect cancer mortality and the duration of latency until death?</p></div><div><h3>Methods</h3><p>A mortality follow-up was conducted with available vital status for 8,476 participants (99 %) and available death certificates for 89.9 % of deceased participants. Standardised mortality ratios (SMR) were calculated for asbestos-related cancers. The SMR of mesothelioma and lung cancer were stratified by exposure duration, cumulative asbestos exposure and smoking. The effect of age at first exposure, cumulative asbestos exposure and smoking on the duration of latency until death was examined using multiple linear regression analysis.</p></div><div><h3>Results</h3><p>The mortality risk of mesothelioma (n = 104) increased with cumulative asbestos exposure but not with exposure duration; the highest mortality (SMR: 23.20; 95 % CI: 17.62–29.99) was observed in participants who performed activities with short extremely high exposures (steam turbine revisions). Lung cancer mortality (n = 215) was not increased (SMR: 1.03; 95 % CI: 0.89–1.17). Median latency until death was 46 (15–63) years for mesothelioma and 44 (15–70) years for lung cancer and deaths occurred between age 64 and 82 years. Latency until death was not influenced by age at first exposure, cumulative exposure, or smoking.</p></div><div><h3>Conclusion</h3><p>Cumulative dose seems to be more appropriate than exposure duration for estimating the risk of mesothelioma death. Additionally, exposure with high cumulative doses in short time should be considered. Since only lung cancer mortality, not incidence, was recorded in this study, lung cancer risk associated with asbestos exposure could not be assessed and the lung cancer mortality was lower than expected probably due to screening effects and improved treatments. The critical time window of death from asbestos-related cancer is between the seventh and ninth decade of life. Future studies should further explore the concept of latency, especially since large ranges are reported throughout the literature.</p></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"195 ","pages":"Article 107899"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141852423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}