Clinical lung cancer最新文献

{"title":"Multicenter Real-World Analysis of Combined MET and EGFR Inhibition in Patients With Non-Small Cell Lung Cancer and Acquired MET Amplification or Polysomy After EGFR Inhibition","authors":"Fabian Acker ,&nbsp;Alexandra Klein ,&nbsp;Anna Rasokat ,&nbsp;Anna Eisert ,&nbsp;Anna Kron ,&nbsp;Petros Christopoulos ,&nbsp;Albrecht Stenzinger ,&nbsp;Jonas Kulhavy ,&nbsp;Horst-Dieter Hummel ,&nbsp;Cornelius F. Waller ,&nbsp;Anne Hummel ,&nbsp;Achim Rittmeyer ,&nbsp;Cornelia Kropf-Sanchen ,&nbsp;Heiner Zimmermann ,&nbsp;Alisa Lörsch ,&nbsp;Diego Kauffmann-Guerrero ,&nbsp;Maret Schütz ,&nbsp;Franziska Herster ,&nbsp;Franziska Thielert ,&nbsp;Melanie Demes ,&nbsp;Sebastian Michels","doi":"10.1016/j.cllc.2024.07.012","DOIUrl":"10.1016/j.cllc.2024.07.012","url":null,"abstract":"<div><h3>Purpose</h3><div>MET amplification is a common resistance mechanism to EGFR inhibition in EGFR-mutant non-small cell lung cancer (NSCLC). Several trials showed encouraging results with combined EGFR and MET inhibition (EGFRi/METi). However, MET amplification has been inconsistently defined and frequently included both polysomy and true amplification.</div></div><div><h3>Methods</h3><div>This is a multicenter, real-world analysis in patients with disease progression on EGFR inhibition and MET copy number gain (CNG), defined as either true amplification (MET to centromere of chromosome 7 ratio [MET-CEP7] ≥ 2) or polysomy (gene copy number ≥ 5, MET-CEP7 &lt; 2).</div></div><div><h3>Results</h3><div>A total of 43 patients with MET CNG were included, 42 of whom were detected by FISH. Twenty-three, 7, and 14 received EGFRi/METi, METi, and SoC, respectively. Patients in the EGFRi/METi cohort exhibited a superior real-world clinical benefit rate, defined as stable disease or better, of 82% (95% confidence interval [CI], 60-95) compared to METi (29%, 4-71) and SoC (50%, 23-77). Median real-world progression-free survival was longer with EGFRi/METi with 9.8 vs. 4.3 months with METi (hazard ratio [HR], 0.19, 95% CI, 0.06-0.57) and 3.7 months with SoC (0.41, 0.18-0.91), respectively. Overall survival was numerically improved. Interaction analysis with treatment and type of CNG (amplification vs. polysomy) suggests that differences were exclusively driven by MET-amplified patients receiving EGFRi/METi (HR for OS, 0.09, 0.01-0.54).</div></div><div><h3>Conclusion</h3><div>In this real-world study, EGFRi/METi showed clinical benefit over METi and SoC. Future studies should focus on the differential impact of the type of MET CNG with a focus on true MET amplification as predictor of response.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages 672-682.e5"},"PeriodicalIF":3.3,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141785169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Exercise During Neoadjuvant Treatments for Non-Small Cell Lung Cancer: The Time is Coming","authors":"Alice Avancini ,&nbsp;Diana Giannarielli ,&nbsp;Lorenzo Belluomini ,&nbsp;Federico Schena ,&nbsp;Michele Milella ,&nbsp;Sara Pilotto","doi":"10.1016/j.cllc.2024.07.015","DOIUrl":"10.1016/j.cllc.2024.07.015","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages e431-e435"},"PeriodicalIF":3.3,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Landscape of Clinically Relevant Genomic Alterations in the Indian Non-small Cell Lung Cancer Patients","authors":"Prerana Jha ,&nbsp;Asim Joshi ,&nbsp;Rohit Mishra ,&nbsp;Ranendra Pratap Biswal ,&nbsp;Pooja Mahesh Kulkarni ,&nbsp;Sewanti Limaye ,&nbsp;Govind Babu ,&nbsp;Ullas Batra ,&nbsp;Prabhat Malik ,&nbsp;Rajiv Kumar ,&nbsp;Minit Shah ,&nbsp;Nandini Menon ,&nbsp;Amit Rauthan ,&nbsp;Moni Kuriakose ,&nbsp;Venkataramanan Ramachandran ,&nbsp;Vanita Noronha ,&nbsp;Prashant Kumar ,&nbsp;Kumar Prabhash","doi":"10.1016/j.cllc.2024.07.011","DOIUrl":"10.1016/j.cllc.2024.07.011","url":null,"abstract":"<div><h3>Background</h3><div>The genomic landscape of non-small cell lung cancer (NSCLC) in the Indian patients remains underexplored. We revealed distinctive genomic alterations of Indian NSCLC patients, thereby providing vital molecular insights for implementation of precision therapies.</div></div><div><h3>Methods</h3><div>We analyzed the genomic profiles of 325 lung adenocarcinoma and 81 lung squamous carcinoma samples from Indian patients using targeted sequencing of 50 cancer related genes. Correlations between genomic alterations and clinical characteristics were computed using statistical analyses. Additionally, we identified distinct features of Indian NSCLC genomes by comparison across different ethnicities.</div></div><div><h3>Results</h3><div>Our genomic analysis revealed several noticeable features of Indian NSCLC patients. Alterations in <em>EGFR</em> (45.8%), <em>TP53</em> (27.4%), <em>ALK</em> (11.4%) and <em>KRAS</em> (10.2%) were predominant in adenocarcinoma, with 68% eligible for targeted therapies. Squamous carcinoma exhibited prevalent alterations in <em>TP53</em> (40.7%), <em>PIK3CA</em> (17.3%), and <em>CDKN2A</em> (8.6%). We observed higher frequency of <em>EGFR</em> alterations (18.5%) in lung squamous carcinoma patients, significantly distinct from other ethnicities reported till date. Beyond established correlations, we observed 60% of PD-L1 negative squamous patients harbored TP53 alterations, suggesting intriguing therapeutic implications.</div></div><div><h3>Conclusions</h3><div>Our data revealed unique genomic variations of adenocarcinoma and squamous carcinoma patients, with significant indications for precision medicine and clinical practice of lung cancers. The study emphasizes the importance of clinical utility of NGS for routine diagnostics.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages e420-e430.e20"},"PeriodicalIF":3.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Lung Cancer Patients With Asymptomatic or Undiagnosed SARS-CoV-2 Infections","authors":"Medha Somisetty ,&nbsp;Philip C. Mack ,&nbsp;Chih-Yuan Hsu ,&nbsp;Yuanhui Huang ,&nbsp;Jorge E. Gomez ,&nbsp;Ananda M. Rodilla ,&nbsp;Jazz Cagan ,&nbsp;Sooyun C. Tavolacci ,&nbsp;Juan Manuel Carreño ,&nbsp;Rachel Brody ,&nbsp;Amy C. Moore ,&nbsp;Jennifer C. King ,&nbsp;Nicholas C. Rohs ,&nbsp;Christian Rolfo ,&nbsp;Paul A. Bunn ,&nbsp;John D. Minna ,&nbsp;Sheena Bhalla ,&nbsp;Florian Krammer ,&nbsp;Adolfo García-Sastre ,&nbsp;Jane C. Figueiredo ,&nbsp;David E. Gerber","doi":"10.1016/j.cllc.2024.07.007","DOIUrl":"10.1016/j.cllc.2024.07.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be spread by individuals unaware they are infected. Such dissemination has heightened ramifications in cancer patients, who may need to visit healthcare facilities frequently, be exposed to immune-compromising therapies, and face greater morbidity from coronavirus disease 2019 (COVID-19). We determined characteristics of (1) asymptomatic, clinically diagnosed, and (2) serologically documented but clinically undiagnosed SARS-CoV-2 infection among individuals with lung cancer.</div></div><div><h3>Patients and methods</h3><div>In a multicenter registry, individuals with lung cancer (regardless of prior SARS-CoV-2 vaccination or documented infection) underwent collection of clinical data and serial blood samples, which were tested for antinucleocapsid protein antibody (anti-N Ab) or IgG (N) levels. We used multivariable logistic regression models to investigate clinical characteristics associated with the presence or absence of symptoms and the presence or absence of a clinical diagnosis among patients with their first SARS-CoV-2 infection.</div></div><div><h3>Results</h3><div>Among patients with serologic evidence or clinically documented SARS-CoV-2 infection, 80/142 (56%) had no reported symptoms at their first infection, and 61/149 (40%) were never diagnosed. Asymptomatic infection was more common among older individuals and earlier-stage lung cancer. In multivariable analysis, non-white individuals with SARS-CoV-2 serologic positivity were 70% less likely ever to be clinically diagnosed (<em>P</em> = .002).</div></div><div><h3>Conclusions</h3><div>In a multicenter lung cancer population, a substantial proportion of SARS-CoV-2 infections had no associated symptoms or were never clinically diagnosed. Because such cases appear to occur more frequently in populations that may face greater COVID-19-associated morbidity, measures to limit disease spread and severity remain critical.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 7","pages":"Pages 612-618"},"PeriodicalIF":3.3,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141839689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The EXcellenT Trial: Exercise in Extended Oncogene Addicted Lung Cancer in Active Treatment","authors":"Chiara Bennati ,&nbsp;Roberto Ferrara ,&nbsp;Sabina Sangaletti ,&nbsp;Stefano Tamberi ,&nbsp;Andrea Spadoni ,&nbsp;Giuseppe Attisani ,&nbsp;Silvano Zanuso ,&nbsp;Jenny Longobardi ,&nbsp;Annalisa Morigi ,&nbsp;Michela Spreafico ,&nbsp;Chiara Zingaretti ,&nbsp;Francesca Fabbri ,&nbsp;Elena Carlotti ,&nbsp;Elisabetta Fabbri ,&nbsp;Livia Turci ,&nbsp;Manolo D'Arcangelo","doi":"10.1016/j.cllc.2024.07.008","DOIUrl":"10.1016/j.cllc.2024.07.008","url":null,"abstract":"<div><h3>Introduction</h3><div>The discovery of oncogenic mutations that drive the growth and progression of Non–small-cell lung cancer (NSCLC) led to the development of a range of molecular targeted therapies. Tyrosine kinase inhibitors (TKIs) improve the overall outcome of patients with oncogene addicted NSCLC, ensure a better compliance to treatment and few side effects compared to traditional chemotherapy. However, the treatment is still completely “drug-centric”, in a population of patients who usually survive for a long time and desire to regain their quality of life. Despite an extensive literature on the importance of complementary treatments and lifestyle promotion, the guidelines on physical exercise are general and usually refer to the entire lung cancer pathology.</div></div><div><h3>Methods and objectives</h3><div>EXcellenT is an Italian monocentric randomized prospective study enrolling 40 patients diagnosed with oncogene-addicted advanced NSCLC in active treatment with TKIs. Patients will be randomized (1:1 ratio) to an ‘interventional’ or a ‘control’ group. In the interventional arm (arm A), participants will receive a 3-month multicomponent personalized physical activity prescription combining a supervised coaching program at the training center and an app-based physical activity schedule at patients home. In the control group (arm B) patients will receive a fitness professional-guided montly session that will result in an unsupervised home-based physical activity counselling. Prospective collection of blood metabolome and immune phenotypes will be performed to investigate the integration with genetic alterations that drive the patient's disease. The overall aim of the project is to evaluate if a tailored physical program may have a significant impact on quality of life and performances of this specific homogeneous subgroup of patients. The exploratory goal is to elucidate a potential link between metabolites, immune parameters and genetic deregulations and how this interplay may be influenced by physical exercise.</div></div><div><h3>Conclusion</h3><div>EXcellent trial aims to propose a new approach to personalized medicine in the specific subgroup of oncogene-addicted NSCLC patients, where targeted therapy is integrated with an equally tailored physical activity program. The homogeneity of this cancer population will provide insights on the influence of exercise on metabolism and immunity during treatment with TKIs.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages e397-e401"},"PeriodicalIF":3.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141689399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Safety and Clinical Activity of Front-line Treatment with Cadonilimab plus Chemotherapy in Advanced/Metastatic Nonsmall Cell Lung Cancer Harboring STK11 Genetic Aberration: A Protocol of Phase II Study","authors":"Huixin Jiang,&nbsp;Ni Sun,&nbsp;Ru Li,&nbsp;Wenhui Guan,&nbsp;Yue Zhu,&nbsp;Zhanhong Xie,&nbsp;Xiaohong Xie,&nbsp;Ming Liu,&nbsp;Xinqing Lin,&nbsp;Chengzhi Zhou","doi":"10.1016/j.cllc.2024.07.006","DOIUrl":"10.1016/j.cllc.2024.07.006","url":null,"abstract":"<div><h3>Background</h3><div>Cadonilimab is a first-in-class bispecific PD-1/CTLA-4 antibody. Serine/threonine kinase (STK11) mutation was shown to be related to low PD-L1 expression and objective response rate (ORR) in nonsmall cell lung cancer (NSCLC), resulting in poor progression-free survival (PFS) and overall survival (OS). Herein, we hypothesized that combining cadonilimab with chemotherapy could enhance antitumor immunity and extend survival in these patients. Consequently, we designed this study to explore the clinical activity and safety of cadonilimab combined with chemotherapy in patients with advanced/metastatic NSCLC harboring STK11 alteration.</div></div><div><h3>Trial design</h3><div>This single-center, open-label, single-arm phase II trial is conducted at the first affiliated hospital of Guangzhou Medical University. Treatment-naïve advanced/metastatic NSCLC patients harboring STK11 mutation will be enrolled in this study. Eligible patients will receive either cadonilimab (10mg/kg on Day 1) plus pemetrexed (500 mg/m²) and carboplatin (AUC = 5) for nonsquamous NSCLC or abraxane (100 mg/m²) and carboplatin (AUC = 5) for squamous NSCLC for 4 cycles, followed by maintenance therapy (cadonilimab plus pemetrexed or abraxane). The treatment will be discontinued when disease progression, intolerability to cadonilimab, and/or chemotherapy occurs. Measurable lesions were assessed according to the Response Evaluation Criteria in Solid Tumors (1.1). The main endpoint is ORR and safety. Subordinate endpoints include PFS, disease control rate, and duration of response.</div></div><div><h3>Results</h3><div>The study commenced enrolment in September 2023, with preliminary findings regarding the primary endpoint anticipated by January 2025.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages e393-e396"},"PeriodicalIF":3.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutations Associated With High-Grade irAEs in NSCLC Patients Receiving Immunotherapies","authors":"Margaret R. Smith ,&nbsp;Yuezhu Wang ,&nbsp;Caroline B. Dixon ,&nbsp;Ralph D'Agostino ,&nbsp;Yin Liu ,&nbsp;Jimmy Ruiz ,&nbsp;George Oliver ,&nbsp;Lance D. Miller ,&nbsp;Umit Topaloglu ,&nbsp;Michael D. Chan ,&nbsp;Michael Farris ,&nbsp;Jing Su ,&nbsp;Kathryn F. Mileham ,&nbsp;Wencheng Li ,&nbsp;Jason M. Grayson ,&nbsp;Thomas Lycan ,&nbsp;Fei Xing","doi":"10.1016/j.cllc.2024.07.003","DOIUrl":"10.1016/j.cllc.2024.07.003","url":null,"abstract":"<div><h3>Objectives</h3><div>Compared to low-grade irAEs, high-grade irAEs are more often dose-limiting and can alter the long-term treatment options for a patient. Predicting the incidence of high-grade irAEs would help with treatment selection and therapeutic drug monitoring.</div></div><div><h3>Materials and methods</h3><div>We performed a retrospective study of 430 stage III and IV patients with non-small cell lung cancer (NSCLC) who received an immune checkpoint inhibitor (ICI), either with or without chemotherapy, at a single comprehensive cancer center from 2015 to 2022. The study team retrieved sequencing data and complete clinical information, including detailed irAEs medical records. Fisher's exact test was used to determine the association between mutations and the presence or absence of high-grade irAEs. Patients were analyzed separately based on tumor subtypes and sequencing platforms.</div></div><div><h3>Results</h3><div>High-grade and low-grade irAEs occurred in 15.2% and 46.2% of patients, respectively. Respiratory and gastrointestinal irAEs were the 2 most common irAEs. The distribution of patients with or without irAEs was similar between ICI and ICI+chemotherapy-treated patients. By analyzing the mutation data, we identified 5 genes (<em>MYC, TEK, FANCA, FAM123B,</em> and <em>MET</em>) with mutations that were correlated with an increased risk of high-grade irAEs. For the adenocarcinoma subtype, mutations in <em>TEK, MYC, FGF19, RET</em>, and <em>MET</em> were associated with high-grade irAEs; while for the squamous subtype, <em>ERBB2</em> mutations were associated with high-grade irAEs.</div></div><div><h3>Conclusion</h3><div>This study is the first to demonstrate that specific tumor mutations correlate with the incidence of high-grade irAEs in patients with NSCLC treated with an ICI, providing molecular guidance for treatment selection and drug monitoring.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages e379-e388"},"PeriodicalIF":3.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141707743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prehabilitation for Older Adults Undergoing Lung Cancer Surgery: A Literature Review and Needs Assessment","authors":"Jane Y. Zhao ,&nbsp;Carolyn Presley ,&nbsp;M. Lucia Madariaga ,&nbsp;Mark Ferguson ,&nbsp;Robert E. Merritt ,&nbsp;Peter J. Kneuertz","doi":"10.1016/j.cllc.2024.07.004","DOIUrl":"10.1016/j.cllc.2024.07.004","url":null,"abstract":"<div><div>Early-stage lung cancer patients are increasingly considered for preoperative systemic therapy. Older adults in particular are among the most vulnerable patients, with little known on how preoperative therapies affect the risk-benefit of surgery. We sought to summarize the current literature and elucidate existing evidence gaps on the effects of prehabilitation interventions relative to age-related functional impairments and the unique needs of older patients undergoing lung cancer surgery. A literature review was performed using PubMed and Google Scholar databases, of all scientific articles published through April 2022 which report on the effects of prehabilitation on patients undergoing lung cancer surgery. We extracted current prehabilitation protocols and their impact on physical functioning, resilience, and patient-reported outcomes of older patients. Emerging evidence suggests that prehabilitation may enhance functional capacity and minimize the untoward effects of surgery for patients following lung resection similar to, or potentially even better than, traditional postoperative rehabilitation. The impact of preoperative interventions on surgical risk due to frailty remains ill-defined. Most studies evaluating prehabilitation include older patients, but few studies report on activities of daily living, self-care, mobility activities, and psychological resilience in older individuals. Preliminary data suggest the feasibility of physical therapy and resilience interventions in older individuals concurrent with systemic therapy. Future research is needed to determine best prehabilitation strategies for older lung cancer patients aimed to optimize age-related impairments and minimize surgical risk.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 7","pages":"Pages 595-600"},"PeriodicalIF":3.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141699511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Efficacy and Safety of Durvalumab Administration Following Chemoradiotherapy in Elderly Patients With Unresectable Locally Advanced Nonsmall Cell Lung Cancer: A Multicenter, Retrospective Study","authors":"Yosuke Kakiuchi ,&nbsp;Koichi Saruwatari ,&nbsp;Kenta Murotani ,&nbsp;Takaaki Tokito ,&nbsp;Toyohisa Iriki ,&nbsp;Jun Iwakawa ,&nbsp;Yoshihiko Sakata ,&nbsp;Naoki Shingu ,&nbsp;Sho Saeki ,&nbsp;Megumi Inaba ,&nbsp;Akira Takaki ,&nbsp;Shunsuke Misono ,&nbsp;Takayuki Suetsugu ,&nbsp;Koichi Azuma ,&nbsp;Keiko Mizuno ,&nbsp;Takuro Sakagami","doi":"10.1016/j.cllc.2024.07.001","DOIUrl":"10.1016/j.cllc.2024.07.001","url":null,"abstract":"<div><h3>Background</h3><div>The PACIFIC trial established durvalumab administration after chemoradiotherapy as the standard of care for unresectable locally advanced nonsmall cell lung cancer (LA-NSCLC). However, the efficacy and safety of durvalumab in elderly patients aged 75 years or above remains unclear. This study aimed to investigate the real-world efficacy and safety of durvalumab for LA-NSCLC, with a specific focus on elderly patients.</div></div><div><h3>Patients and Methods</h3><div>We reviewed 214 patients who received durvalumab out of 278 patients with unresectable LA-NSCLC who underwent chemoradiotherapy at 7 institutions between July 2018 and March 2022. Propensity score matching (PSM) analysis was performed to evaluate the efficacy of durvalumab in elderly patients.</div></div><div><h3>Results</h3><div>The 2-year progression-free survival (PFS) and 2-year overall survival (OS) rates were 42.2% (95% confidence interval [CI], 34.7%-49.5%) and 77.1% (95% CI, 70.1-82.7%), respectively. Grade ≥ 3 immune-related adverse events (irAEs) occurred in 8.2% of patients. PSM analysis revealed that OS was significantly shorter in elderly patients (≥ 75 years) than in younger patients (&lt; 75 years) (hazard ratio [HR]; 95% CI, 1.39-8.99; <em>P</em> = .008), whereas PFS did not differ significantly between the 2 groups (HR: 1.50, 95% CI, 0.84-2.68, <em>P</em> = .169). The frequency of irAEs did not differ between these groups.</div></div><div><h3>Conclusions</h3><div>The real-world efficacy and safety of durvalumab administration following chemoradiotherapy for LA-NSCLC coincided with the PACIFIC trial's findings. Disease control achieved with this protocol did not differ significantly between elderly and younger patients but had acceptable tolerability, demonstrating its benefit even in elderly LA-NSCLC patients aged 75 years or above.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages 661-671.e7"},"PeriodicalIF":3.3,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141688468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Trial Report: A Multicenter Phase I/Ib study of Capmatinib Plus Trametinib in Patients With Metastatic Nonsmall Cell Lung Center Harboring MET Exon 14 Skipping Mutations and Other MET-Alterations","authors":"Matthew S. Lara ,&nbsp;Jonathan W. Riess ,&nbsp;Jonathan W. Goldman ,&nbsp;Fei Jiang ,&nbsp;Trever G. Bivona ,&nbsp;Collin M. Blakely","doi":"10.1016/j.cllc.2024.07.002","DOIUrl":"10.1016/j.cllc.2024.07.002","url":null,"abstract":"<div><h3>Introduction</h3><div>MET tyrosine kinase inhibitor (TKI) therapy is associated with improved outcomes in patients with nonsmall cell lung cancer (NSCLC) harboring a MET alteration, including MET exon 14 (METex14) skipping mutation, MET amplification, or MET fusion. However, primary or acquired resistance to TKI therapy ultimately develops. In preclinical models, hyperactivation of MAPK signaling was shown to promote resistance to MET TKI; resistance was overcome by co-treatment with a MET inhibitor and a MEK inhibitor. This phase I/Ib study offers a potential combination strategy simultaneously targeting MET (with capmatinib) and MEK signaling (with trametinib) to overcome resistance to MET inhibitor monotherapy in METex14 NSCLC.</div></div><div><h3>Methods</h3><div>In the dose escalation phase, a minimum of 6 and maximum of 18 patients will be enrolled using a conventional 3+3 design with the primary endpoint of identifying a recommended phase 2 dose (RP2D) of capmatinib in combination with trametinib. Once the RP2D is identified, patients will continue to enroll in a dose expansion phase to a total of 15 patients. The primary endpoint of the dose expansion phase is to further characterize the safety profile of the combination.</div></div><div><h3>Conclusion</h3><div>This phase I/Ib clinical trial will assess the safety and efficacy of combination capmatinib and trametinib in NSCLC patients whose tumors harbor METex14 skipping mutations, MET amplification, or MET fusion and had developed progressive disease on single agent MET inhibitor therapy.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 8","pages":"Pages 732-737"},"PeriodicalIF":3.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}