Lung Cancer最新文献

{"title":"Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia","authors":"Yuki Kato ,&nbsp;Hibiki Udagawa ,&nbsp;Shingo Matsumoto ,&nbsp;Hiroki Izumi ,&nbsp;Yuichiro Ohe ,&nbsp;Terufumi Kato ,&nbsp;Kazumi Nishino ,&nbsp;Shingo Miyamoto ,&nbsp;Sachiko Kawana ,&nbsp;Kenichi Chikamori ,&nbsp;Masato Shingyoji ,&nbsp;Yuki Sato ,&nbsp;Yuji Takada ,&nbsp;Ryo Toyozawa ,&nbsp;Koichi Azuma ,&nbsp;Yu Tanaka ,&nbsp;Tetsuya Sakai ,&nbsp;Yuji Shibata ,&nbsp;Eri Sugiyama ,&nbsp;Kaname Nosaki ,&nbsp;Koichi Goto","doi":"10.1016/j.lungcan.2024.107992","DOIUrl":"10.1016/j.lungcan.2024.107992","url":null,"abstract":"<div><h3>Introduction</h3><div><em>HER2</em> mutations are reported to occur in 2%–5% of all cases of non-small cell lung cancer (NSCLC). The clinical outcomes in patients with <em>HER2</em>-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear.</div></div><div><h3>Methods</h3><div>Using the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with <em>HER2</em>-mutant NSCLC were investigated.</div></div><div><h3>Results</h3><div>Of the 15,251 patients with NSCLC enrolled in the LC-SCRUM-Asia database, tumor <em>HER2</em> mutations were detected in 402 patients (2.6 %). The most common subtype of <em>HER2</em> mutations was exon 20 in-frame insertions (79 %), followed in frequency by mutations in the tyrosine kinase domain other than Exon20ins (10 %) and mutations in extracellular domains (7 %). NSCLCs harboring <em>HER2</em> mutations showed a higher tumor mutation burden (TMB) as compared with NSCLCs harboring <em>EGFR</em> mutations or <em>ALK</em> fusions (median: 4.22 vs. 2.54 and 2.52 mutation per megabase, respectively). Of the 402 patients, 268 patients had received platinum-based chemotherapy with ICIs (Chemo-ICI, n = 95) or without ICI (Chemo-alone, n = 173) as 1st line treatment. The progression-free survival (PFS) was significantly longer in the Chemo-ICI group as compared with the Chemo-alone group (median 8.5 vs. 6.3 months; HR [95 %CI]: 0.66 [0.50–0.88]; <em>P</em> &lt; 0.005). Multivariate analysis identified use of ICIs in addition to platinum-based chemotherapy as an independent favorable prognostic factor for PFS. There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57–1.12], <em>P</em> = 0.20).</div></div><div><h3>Conclusions</h3><div>Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with <em>HER2</em>-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with <em>HER2</em>-mutant NSCLC receiving platinum-based chemotherapy with ICIs.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107992"},"PeriodicalIF":4.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446990","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":"Reassessing pembrolizumab dosing in NSCLC for methodological and clinical accuracy","authors":"Da Qiu ,&nbsp;Chao Qiu ,&nbsp;Yongneng Wang ,&nbsp;Dan Shan","doi":"10.1016/j.lungcan.2024.107989","DOIUrl":"10.1016/j.lungcan.2024.107989","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107989"},"PeriodicalIF":4.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432439","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":"Afatinib plus bevacizumab combination after osimertinib resistance in advanced EGFR-mutant non-small cell lung cancer: Phase II ABCD-study","authors":"Akito Hata ,&nbsp;Nobuyuki Katakami ,&nbsp;Naoto Takase ,&nbsp;Kayoko Kibata ,&nbsp;Yuta Yamanaka ,&nbsp;Motohiro Tamiya ,&nbsp;Masahide Mori ,&nbsp;Takashi Kijima ,&nbsp;Satoshi Morita ,&nbsp;Kazuko Sakai ,&nbsp;Kazuto Nishio","doi":"10.1016/j.lungcan.2024.107988","DOIUrl":"10.1016/j.lungcan.2024.107988","url":null,"abstract":"<div><h3>Introduction</h3><div>Many clinical studies showed a synergy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor inhibitors. We hypothesized afatinib plus bevacizumab exerts clinical potency after developing various osimertinib resistant mechanisms.</div></div><div><h3>Methods</h3><div><em>EGFR</em>-mutant non-small cell lung cancer patients were enrolled after osimertinib resistance. Afatinib at 30–40 mg/day and bevacizumab at 15 mg/kg tri-weekly were administered until progression. Plasma/histologic rebiopsied samples after osimertinib failure were analyzed to examine resistant mechanisms: gene alterations/copy-number gain using cancer personalized profiling by deep sequencing.</div></div><div><h3>Results</h3><div>Between January 2018 and October 2020, 28 patients were enrolled. Response and disease control rates were 17.9 % and 78.6 %, respectively. Median duration of response was 9.0 (range, 4.2–22.3) months. Median progression-free and overall survivals were 2.7 and 9.3 months, respectively. Twenty-eight (100 %) plasma and/or 21 (75 %) histologic rebiopsies identified: 17 (61 %) <em>TP53</em>; 15 (54 %) <em>T790M</em>; 9 (32 %) uncommon <em>EGFR</em>; 9 (32 %) <em>MET</em>; 6 (21 %) <em>C797S</em>; 3 (11 %) <em>BRAF</em>; 2 (7 %) <em>HER2</em>; 2 (7 %) <em>KRAS</em>; and 2 (7 %) <em>PI3K</em> mutations. One (17 %) of 6 <em>C797S</em> patients showed complete response. Three (33 %) of 9 uncommon <em>EGFR</em>-mutated patients achieved radiographic response. Neither 15 <em>T790M</em>-positive nor 6 <em>EGFR</em> downstream signaling mutations: <em>BRAF</em>; <em>KRAS</em>; or <em>PI3K</em>-positive patients responded, but 5 (38 %) of 13 <em>T790M</em>-negative patients responded. Adverse events ≥ grade 3 and incidence ≥ 5 % were: hypertension (29 %); proteinuria (7 %); and diarrhea (7 %). There were neither treatment-related death nor interstitial lung disease.</div></div><div><h3>Conclusions</h3><div>Selected population could obtain clinical benefit from afatinib plus bevacizumab, based on rebiopsy results after osimertinib resistance.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107988"},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406587","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":"Crispr-mediated genome editing reveals a preponderance of non-oncogene addictions as targetable vulnerabilities in pleural mesothelioma","authors":"Duo Xu ,&nbsp;Shun-Qing Liang ,&nbsp;Min Su ,&nbsp;Haitang Yang ,&nbsp;Rémy Bruggmann ,&nbsp;Simone Oberhaensli ,&nbsp;Zhang Yang ,&nbsp;Yanyun Gao ,&nbsp;Thomas M. Marti ,&nbsp;Wenxiang Wang ,&nbsp;Ralph A. Schmid ,&nbsp;Yongqian Shu ,&nbsp;Patrick Dorn ,&nbsp;Ren-Wang Peng","doi":"10.1016/j.lungcan.2024.107986","DOIUrl":"10.1016/j.lungcan.2024.107986","url":null,"abstract":"<div><div>Pleural mesothelioma (PM) is an aggressive cancer with limited treatment options. In particular, the frequent loss of tumor suppressors, a key oncogenic driver of the disease that is therapeutically intractable, has hampered the development of targeted cancer therapies. Here, we interrogate the PM genome using CRISPR-mediated gene editing to systematically uncover PM cell susceptibilities and provide an evidence-based rationale for targeted cancer drug discovery. This analysis has allowed us to identify with high confidence numerous known and novel gene dependencies that are surprisingly highly enriched for non-oncogenic pathways involved in response to various stress stimuli, in particular DNA damage and transcriptional dysregulation. By integrating genomic analysis with a series of <em>in vitro</em> and <em>in vivo</em> functional studies, we validate and prioritize several non-oncogene addictions conferred by CDK7, CHK1, HDAC3, RAD51, TPX2, and UBA1 as targetable vulnerabilities, revealing previously unappreciated aspects of PM biology. Our findings support the growing consensus that stress-responsive non-oncogenic signaling plays a key role in the initiation and progression of PM and provide a functional blueprint for the development of unprecedented targeted therapies to combat this formidable disease.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107986"},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391654","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":"Stereologic consequences of iatrogenic collapse: The morphology of adenocarcinoma in situ overlaps with invasive patterns. Proposal for a necessary modified classification of pulmonary adenocarcinomas","authors":"Federica Filipello ,&nbsp;Hans Blaauwgeers ,&nbsp;Birgit Lissenberg-Witte ,&nbsp;Andreas Schonau ,&nbsp;Claudio Doglioni ,&nbsp;Gianluigi Arrigoni ,&nbsp;Teodora Radonic ,&nbsp;Idris Bahce ,&nbsp;Arthur Smit ,&nbsp;Chris Dickhoff ,&nbsp;Antonio Nuccio ,&nbsp;Alessandra Bulotta ,&nbsp;Yuko Minami ,&nbsp;Masayuki Noguchi ,&nbsp;Francesca Ambrosi ,&nbsp;Erik Thunnissen","doi":"10.1016/j.lungcan.2024.107987","DOIUrl":"10.1016/j.lungcan.2024.107987","url":null,"abstract":"<div><div>Recognizing non-invasive growth patterns is necessary for correct diagnosis, invasive size determination and pT-stage in resected non-small cell lung carcinoma. Due to iatrogenic collapse after resection, the distinction between adenocarcinoma <em>in-situ</em> (AIS) and invasive adenocarcinoma may be difficult. The aim of this study is to investigate the complex morphology of non-mucinous non-invasive patterns of AIS in resection specimen with iatrogenic collapse, and to relate this to follow-up.</div><div>The effects of iatrogenic collapse on the morphology of collapsed AIS were simulated in a mathematical model. Three dimensional related criteria applied in a modified classification, using also cytokeratin 7 and elastin as additional stains, in two independent retrospective cohorts of primary pulmonary adenocarcinomas ≤3 cm resection specimen with available follow-up information.</div><div>The model demonstrated that infolding of alveolar walls occurs during iatrogenic collapse and lead to a significant increase in tumor cell heights in maximal collapse areas, compared to less collapsed areas. The morphology of infolded AIS overlaps with patterns described as papillary and acinar adenocarcinoma according to the WHO classification, necessitating an adaptation.</div><div>The modified classification incorporates recognition of iatrogenic and biologic collapse, tangential cutting effect true invasion and surrogate markers of invasion i.e. grey zone, covering a multilayering falling short of micropapillary, cribriform and solid alveolar filling growth. The use of elastin and CK7 staining aids in the morphologic recognition of iatrogenic collapsed AIS and the distinction from invasive adenocarcinoma. Out of a total of 70 resection specimens 1 case was originally classified as AIS and 9 were reclassified as iatrogenic collapsed AIS. Patients with collapsed AIS showed a 100 % recurrence-free survival after a mean follow-up time of 69.5 months.</div><div>With the current WHO classification, AIS is overdiagnosed as invasive adenocarcinoma due to infolding. The modified classification facilitates the diagnosis of AIS.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107987"},"PeriodicalIF":4.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400695","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":"Integrated analysis of older adults and patients with renal dysfunction in the IMpower130 and IMpower132 randomized controlled trials for advanced non-squamous non-small cell lung cancer","authors":"Makoto Nishio ,&nbsp;Satoshi Watanabe ,&nbsp;Hibiki Udagawa ,&nbsp;Naoko Aragane ,&nbsp;Yuki Nakagawa ,&nbsp;Yuki Kobayashi ,&nbsp;Haruhiro Saito","doi":"10.1016/j.lungcan.2024.107859","DOIUrl":"10.1016/j.lungcan.2024.107859","url":null,"abstract":"<div><h3>Objectives</h3><div>This exploratory integrated analysis of the randomized Phase III IMpower130 and IMpower132 trials evaluated the efficacy and safety of atezolizumab plus platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC) who were aged ≥75 years or had renal dysfunction.</div></div><div><h3>Materials and methods</h3><div>Chemotherapy-naïve patients with stage IV non-squamous NSCLC received atezolizumab-containing therapy or platinum-doublet chemotherapy in IMpower130 and IMpower132. This integrated analysis assessed efficacy (including overall survival [OS], progression-free survival [PFS], and objective response rates) and safety in the integrated population and in patients ≥75 years old. Subgroup analyses by baseline creatinine clearance (&lt;45, 45 to &lt;60, and ≥60 mL/min) were conducted for each study population.</div></div><div><h3>Results</h3><div>This integrated analysis included 1224 patients: 737 in the atezolizumab-containing group and 487 in the chemotherapy group. At data cutoff, the hazard ratio (HR) for PFS was 0.62 (95% CI: 0.54–0.71) in the integrated population and 0.59 (95% CI: 0.40–0.88) in the ≥75-years subgroup. The HR for OS was 0.81 (95% CI: 0.68–0.95) in the integrated population and 0.65 (95% CI: 0.39–1.07) in the ≥75-years subgroup. PFS and OS benefits with the atezolizumab combination vs chemotherapy were maintained across subgroups with varying renal function in IMpower130, and PFS benefits were maintained across subgroups in IMpower132.</div></div><div><h3>Conclusions</h3><div>The results of this post hoc integrated analysis of IMpower130 and IMpower132 show that the efficacy and safety of atezolizumab plus platinum-doublet chemotherapy is maintained in patients ≥75 years old and in patients with renal dysfunction.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107859"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913174","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":"Cryobiopsy versus fine-needle aspiration for shape-sensing robotic-assisted sampling of small lung nodules","authors":"David Abia-Trujillo ,&nbsp;Rodrigo Funes-Ferrada ,&nbsp;Alejandra Yu Lee-Mateus ,&nbsp;Alanna Barrios-Ruiz ,&nbsp;Andras Khoor ,&nbsp;Neal M. Patel ,&nbsp;Britney N. Hazelett ,&nbsp;Kelly S. Robertson ,&nbsp;Sebastian Fernandez-Bussy","doi":"10.1016/j.lungcan.2024.107967","DOIUrl":"10.1016/j.lungcan.2024.107967","url":null,"abstract":"<div><h3>Introduction</h3><div>Shape-sensing Robotic-assisted Bronchoscopy (ssRAB) has emerged as a promising tool for improved performance when sampling pulmonary nodules (PPN). Previous studies suggest that the 1.1 mm cryoprobe is as effective compared to fine needle aspiration (FNA), for different lesions sizes. We aim to compare the 1.1 mm cryoprobe performance to FNA for sampling PPN &lt; 20 mm with ssRAB.</div></div><div><h3>Material and Methods</h3><div>We conducted a retrospective cohort study from November 2022 to February 2024 of patients who underwent ssRAB with cryobiopsy for evaluation of PPN. We compared the diagnostic yield and sensitivity for malignancy of cryobiopsy and FNA for the same PPN. Descriptive statistical analysis was conducted using the McNemar’s Test and Comparison of proportion. Multivariate logistic regression assessed the impact of PPN characteristics on the yield of each tool.</div></div><div><h3>Results</h3><div>We included 256 patients, with a combined 284 procedures, and 324 nodules sampled. The median maximum and minimum nodule size was 1.6 cm (IQR 1.17–2.4) and 1.17 cm (IQR 0.86–1.7) respectively. The overall ssRAB diagnostic yield was 93.8 % and sensitivity for malignancy was 97.5 %. Cryobiopsy had a diagnostic yield of 92 % and sensitivity of 96 %, FNA had a 70.4 % and 79.29 % respectively (<em>P</em> &lt; 0.001). Cryobiopsy had a significantly higher performance compared to FNA across the analyzed categories (<em>P</em> &lt; 0.05), except for the sensitivity of mixed-type lesions (<em>P</em> = 0.11). PPN &lt; 10 mm and ≥ 10 mm − &lt;15 mm sampled with FNA, had lower odds of achieving a diagnosis compared to the ≥ 20 mm group (OR = 0.305 IC95%: 0.142–0.65, p &lt; 0.001; OR = 0.497 IC95%: 0.263–0.939, p = 0.031, respectively). Complications occurred in 5.98 % (N = 17) of cases.</div></div><div><h3>Conclusion</h3><div>Cryobiopsy demonstrates a statistically higher diagnostic yield and sensitivity for malignancy compared to FNA. Remarkably, FNA showed reduced diagnostic odds in PPN &lt; 15 mm. ssRAB with cryobiopsy could enhance PPN diagnostic yield, leading to earlier lung cancer diagnosis and improve long-term survival rates.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107967"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349509","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":"Can therapeutic drug monitoring of lorlatinib help us design the right CROWN?","authors":"Molly Li,&nbsp;Ross A. Soo","doi":"10.1016/j.lungcan.2024.107965","DOIUrl":"10.1016/j.lungcan.2024.107965","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107965"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349508","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":"Safety assessment of KRAS (G12C) inhibitors based on the FDA Adverse Event Reporting System (FAERS) database: A real-world pharmacovigilance study","authors":"Maohua Chen ,&nbsp;Yaping Huang ,&nbsp;Shaojun Jiang ,&nbsp;Chengjie Ke","doi":"10.1016/j.lungcan.2024.107966","DOIUrl":"10.1016/j.lungcan.2024.107966","url":null,"abstract":"<div><h3>Objectives</h3><div><em>KRAS (G12C)</em> inhibitors (sotorasib and adagrasib) have approved treatment in patients with <em>KRAS (G12C)</em>-mutated non-small cell lung cancer (NSCLC). The post-marketing data concerning <em>KRAS (G12C)</em> inhibitors remain limited, and the outcomes of relevant studies are yet to yield conclusive evidence supporting the long-term safety of <em>KRAS (G12C)</em> inhibitors.</div></div><div><h3>Materials and methods</h3><div>This investigation comprehensively assessed adverse events (AEs) attributed to <em>KRAS (G12C)</em> inhibitors by employing advanced data mining techniques, utilizing the FDA Adverse Event Reporting System (FAERS). The dataset encompasses the period from the first quarter of 2021 to the first quarter of 2024. A disproportionality analysis was conducted to quantify the correlation between <em>KRAS (G12C)</em> inhibitors and AEs. The metrics employed for the evaluation of disproportionality comprise the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayesian geometric mean (EBGM).</div></div><div><h3>Results</h3><div>A total of 2,253 and 486 reports were identified as related to sotorasib and adagrasib, with the identification of 51 and 26 preferred terms, respectively. The most frequent AEs of sotorasib comprised diarrhoea (ROR 5.27), hepatotoxicity (ROR 38.09), alanine aminotransferase increased (ROR 17.41), aspartate aminotransferase increased (ROR 20.88), and hepatic function abnormal (ROR 19.88). The most common AEs of adagrasib included diarrhoea (ROR 4.21), nausea (ROR 3.84), vomiting (ROR 5.36), decreased appetite (ROR 4.79), and dehydration (ROR 7.00). A relatively reduced risk of hepatotoxicity but a increased risk of serious AEs in adagrasib compared to sotorasib (<em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Our findings would provide valued evidence for healthcare professionals to recognize AEs associated with <em>KRAS (G12C)</em> inhibitors and differences between sotorasib and adagrasib, and guide their clinical practice.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"196 ","pages":"Article 107966"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349510","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 prediction of treatment outcome in NSCLC patients harboring an EGFR exon 20 mutation using molecular modeling","authors":"F. Zwierenga ,&nbsp;L. Zhang ,&nbsp;J. Melcr ,&nbsp;E. Schuuring ,&nbsp;B.A.M.H. van Veggel ,&nbsp;A.J. de Langen ,&nbsp;H.J.M. Groen ,&nbsp;M.R. Groves ,&nbsp;A.J. van der Wekken","doi":"10.1016/j.lungcan.2024.107973","DOIUrl":"10.1016/j.lungcan.2024.107973","url":null,"abstract":"<div><h3>Introduction</h3><div>The structural effect of uncommon heterogenous in-frame deletion and/or insertion mutations within exon 20 (EGFRex20+) in relation to therapy response is poorly understood. This study aims to elucidate the structural alterations caused by EGFRex20+ mutations and correlate these changes with patient responses.</div></div><div><h3>Material and method</h3><div>We selected EGFRex20+ mutations from advanced NSCLC patients in the Position20 and AFACET studies for computational analysis. Homology models representing both inactive and active conformations of these mutations were generated using the Swiss-Model server. Molecular docking studies with EGFR-TKIs was conducted using smina, followed by Molecular Dynamic (MD) simulations performed with GROMACS. These computational findings were compared with clinical outcomes to evaluate their potential in predicting patient response.</div></div><div><h3>Results</h3><div>Our docking studies of 29 EGFRex20+ mutations revealed that the binding energies of afatinib, osimertinib, zipalertinib, and sunvozertinib, compared to the wild type, do not significantly impact either TKI’s efficacy. MD simulations for eight EGFRex20+ mutations (A763_Y764insFQEA, A767_V769dup, S768_D770dup, D770_N771insG, D770_P772dup, N771_H773dup, H773_V774insY and H773_V774delinsLM) revealed varying degrees of instability. For six variants, predicted activation based on the αC-helix stability and orientation, as well as TKI sensitivity, aligned well with clinical observations from the Position20 and AFACET studies. Two mutations (D770_N771insG and N771_H773dup) predicted as poor to moderate responders, showed minimal activation of the αC-helix region, warranting further investigation.</div></div><div><h3>Conclusion</h3><div>In conclusion, MD simulations can effectively predict patient outcomes by connecting computational results with clinical data and advancing our understanding of EGFR mutations and their therapeutic responses.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"197 ","pages":"Article 107973"},"PeriodicalIF":4.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391655","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}