Lung Cancer最新文献

{"title":"CT-assessed sarcopenia and immune-related adverse events in patients with lung cancer: A competing risk time-to-event analysis.","authors":"Erick Suazo-Zepeda, Alain R Viddeleer, Willemijn J Maas, Douwe Postmus, Marjolein A Heuvelmans, T Jeroen N Hiltermann, Geertruida H De Bock","doi":"10.1016/j.lungcan.2024.108054","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108054","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs). This study investigates the relationship between CT-assessed sarcopenia and irAEs in patients with lung cancer who are receiving ICIs.</p><p><strong>Methods: </strong>Patients were enrolled if they had lung cancer treated with ICIs at the University Medical Center Groningen (2015-2021) and had undergone low-dose CT scans that included the third lumbar vertebral level (L3). CT-assessed sarcopenia was defined based on reported L3 skeletal muscle mass index (L3SMI) thresholds. Patients were categorized into no, any-grade, and severe irAE groups. The association between CT-assessed sarcopenia and irAEs was assessed by competing risk time-to-event analysis, accounting for the risk of death. Sub-distribution hazard ratios (_SDHR) were calculated using Fine-Gray regression models adjusted for relevant confounders. The association between CT-assessed sarcopenia and overall survival (OS) was evaluated through survival analyses.</p><p><strong>Results: </strong>We included 363 patients; most were male (60.9 %), had favorable Eastern Cooperative Oncology Group (ECOG) performance statuses (0-1; 90.1 %), had stage IV disease (92.8 %), and received ICI monotherapy (82.9 %). Of these, 45.6 % developed any-grade irAEs and 21 % developed severe irAEs. Endocrine disorders were the most common mild irAEs (24.8 %), while respiratory disorders were the most common severe irAEs (24.7 %). CT-assessed sarcopenia was more prevalent in the no irAE group (87 %) compared with the any-grade (77 %) and severe (79 %) irAE groups. Presence of CT-assessed sarcopenia was associated with a lower risk of developing any irAEs (_SDHR = 0.62 [95 % CI: 0.41-0.92]). No significant association was found between CT-assessed sarcopenia and severe irAEs (fully adjusted model, _SDHR = 0.74 [95 % CI: 0.39-1.4]), or between CT-assessed sarcopenia and OS.</p><p><strong>Conclusion: </strong>CT-assessed sarcopenia is associated with a reduced risk of any irAEs in patients with lung cancer receiving ICIs, possibly because higher muscle mass enhances the host response to immunological stimulation. Recognizing sarcopenia as a predictive factor for irAEs is relevant for personalizing treatments.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108054"},"PeriodicalIF":4.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872512","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 novel clinical brain prognostic index for KRAS-mutated lung cancer and brain metastases (KRAS-BPI): Real-world evidence from two large European centers.","authors":"Ioannis Zerdes, Caroline Kamali, Berglind Johannsdottir, Miriam Blasi, Christin Assmann, Daniel Kazdal, Albrecht Stenzinger, Marcus Skribek, Simon Ekman, Petros Christopoulos, Georgios Tsakonas","doi":"10.1016/j.lungcan.2024.108065","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108065","url":null,"abstract":"<p><strong>Introduction: </strong>Several prognostic scores were developed for non-small-cell lung cancer (NSCLC) patients with brain metastases (BM), though limited data reported for the KRAS-mutated subgroup. KRAS-targeted therapies have improved extracranial and intracranial response, highlighting the need for reliable prognostic biomarkers.</p><p><strong>Methods: </strong>A retrospective cohort (2010-2020) comprising 220 patients with BM KRAS-mutated NSCLC from two large academic Thoracic Oncology centers (Karolinska and Heidelberg) was analyzed. Clinicopathological parameters were collected from electronic health records. Prognostic factors of overall survival from BM diagnosis (BM-OS) were identified using Cox regression models.</p><p><strong>Results: </strong>The median age at diagnosis was 65 years, with a female predominance (55.9 %). Adenocarcinoma was the dominant histological subtype, performance status (PS) was 0-2 in 91 % of the patients and one-third had > 4 BMs. Variables independently correlated with BM-OS included the presence of primary BM disease, PS, age, symptomatic CNS disease, extracranial metastases and number of BM, and were used to design a new KRAS-Brain Prognostic Index (KRAS-BPI). Patients with high-index score showed significantly longer BM-OS, compared to intermediate/low-index groups (median BM-OS = 30.0 vs 9.0 vs 2.0 months, respectively).</p><p><strong>Conclusions: </strong>In the largest real-word data study of KRAS-mutated NSCLC patients with BM, we developed a novel prognostic tool for improved patient stratification.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108065"},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872493","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 combined model of circulating tumor DNA methylated SHOX2/SCT/HOXA7 and clinical features facilitates the discrimination of malignant from benign pulmonary nodules.","authors":"Lu He, Biao Zhang, Chu Zhou, Qi Zhao, Yongsheng Wang, Yuan Fang, Zijian Hu, Ping Lv, Liyun Miao, Rusong Yang, Jun Yang","doi":"10.1016/j.lungcan.2024.108064","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108064","url":null,"abstract":"<p><strong>Background: </strong>Despite the advancements in early lung cancer detection attributed to the widespread use of low-dose computed tomography (LDCT), this technology has also led to an increasing number of pulmonary nodules (PNs) of indeterminate significance being identified. Therefore, this study was aimed to develop a model that leverages plasma methylation biomarkers and clinical characteristics to distinguish between malignant and benign PNs.</p><p><strong>Methods: </strong>In a training cohort of 210 patients with PNs, we evaluated plasma circulating tumor DNA (ctDNA) for the presence of three lung cancer-specific methylation markers: SHOX2, SCT, and HOXA7. Subsequently, we constructed a combined model utilizing methylated SHOX2/SCT/HOXA7 (mSHOX2/SCT/HOXA7) ctDNA levels, the largest nodule size measured by LDCT, and age, employing the binary logistic regression algorithm. Furthermore, we compared the diagnostic performances of the combined model with the Mayo Clinic model and the single mSHOX2/SCT/HOXA7 model by analyzing the area under the receiver operating characteristic curve (AUC) for each.</p><p><strong>Results: </strong>The combined model demonstrated an impressive AUC of 0.87 and an accuracy of 0.75 in the training cohort, using pathologic diagnoses as the gold standard. This performance was significantly superior to that of the single mSHOX2/SCT/HOXA7 panel (AUC = 0.81, P < 0.0001) and the Mayo model (AUC = 0.65, P = 0.0005). Further validation in a cohort of 82 patients with PNs confirmed the diagnostic value of the combined model. Additionally, we observed that as the size of the nodule increased, the diagnostic accuracy of the combined model also improved.</p><p><strong>Conclusions: </strong>A combined model incorporating the ctDNA-based methylation status of SHOX2/SCT/HOXA7 genes, the largest nodule size measured by LDCT, and age can serve as a supplementary approach to LDCT for lung cancer. This model enhances the precision in identifying high-risk individuals and optimizes the clinical management strategies for PNs detected by CT.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108064"},"PeriodicalIF":4.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872491","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":"Impact of locoregional recurrence versus distant metastasis on overall survival in patients with Non-Small cell lung cancer after Surgery: A secondary analysis of PORT-C RCT.","authors":"Zeliang Ma, Yunsong Liu, Yongxing Bao, Meiqi Wang, Xu Yang, Yu Men, Jianyang Wang, Lei Deng, Yirui Zhai, Chen Hu, Nan Bi, Luhua Wang, Zhouguang Hui","doi":"10.1016/j.lungcan.2024.108063","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108063","url":null,"abstract":"<p><strong>Purpose: </strong>The therapeutic advantage of postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) has not been shown to benefit overall survival (OS) according to two randomized controlled trials (RCTs), albeit an enhancement in locoregional-free survival was observed. We aimed to evaluate the relative influence of locoregional recurrence (LR) and distant metastasis (DM) on OS for patients with NSCLC after surgery.</p><p><strong>Methods: </strong>This was a secondary analysis of PORT-C RCT. Patients with pN2 NSCLC undergoing complete resection followed by chemotherapy were included. A dynamic prediction model was developed to evaluate the impact of LR and DM on OS. The endpoint was OS. Age, sex, smoking history, histology, Karnofsky Performance Status, tumor side, T stage, and positive lymph node were baseline factors, whereas LR and DM status were time-dependent covariates.</p><p><strong>Results: </strong>In total, 364 patients were eligible, including 214 and 150 in the non-PORT and PORT groups, respectively. DM significantly decreased OS in both the non-PORT (odds ratio [OR], 4.74; 95 % CI, 2.70-8.30; P < 0.01) and PORT (OR, 5.43; 95 % CI, 2.56-11.48; P < 0.01) groups. LR also significantly impacted OS in the non-PORT (OR, 2.09; 95 % CI, 1.12-3.93; P = 0.02) and the PORT (OR, 3.44; 95 % CI, 1.53-7.75; P < 0.01) groups. Multivariate Cox analysis identified the pT stage, positive lymph nodes, and histology as variables correlated with DM. A nomogram was developed to estimate the risk of DM. PORT did not significantly enhance OS in either the low (HR, 1.42; 95 % CI, 0.63-3.19, P = 0.40) or high-risk (HR, 0.62; 95 % CI, 0.35-1.09, P = 0.10) subgroup but in the medium-risk subgroup (HR, 0.20; 95 % CI, 0.05-0.86, P = 0.02).</p><p><strong>Conclusion: </strong>DM and LR significantly impacted OS in patients with NSCLC after surgery. DM emerged as the dominant failure pattern, emphasizing more effective control of DM. PORT was beneficial for patients with a medium risk of DM.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108063"},"PeriodicalIF":4.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864323","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":"An open-label, randomized phase III study of early switch maintenance vs delayed second-line nivolumab in advanced stage squamous non-small cell lung cancer (NSCLC) patients after standard first-line platinum-based chemotherapy-EDEN trial GOIRC 04-2016.","authors":"Francesco Gelsomino, Luca Boni, Marcello Tiseo, Serena Ricciardi, Danilo Rocco, Diego L Cortinovis, Manuela Proietto, Alessio Cogoni, Giulia Pasello, Andrea Camerini, Francesca Sperandi, Ida Colantonio, Giulio Metro, Francesca Mazzoni, Editta Baldini, Antonello Veccia, Elisa Bennicelli, Anna Cecilia Bettini, Michele Tognetto, Andrea Ardizzoni","doi":"10.1016/j.lungcan.2024.108059","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108059","url":null,"abstract":"<p><strong>Background: </strong>As for squamous (Sq)-NSCLC, Checkmate-017 trial showed a significant overall survival (OS) improvement in favor of Nivolumab (Nivo) over Docetaxel in 2nd-line. We hypothesized that anticipating Nivo use, as early switch maintenance after 1st-line chemotherapy (CHT), might have improved survival as compared to delayed 2nd-line treatment.</p><p><strong>Methods: </strong>EDEN was an open-label, 2-arm, phase III study which randomized (1:1) stage IIIB/IV Sq-NSCLC pts non-progressive after 1st-line platinum-based CHT, to receive early Nivo as switch maintenance (Arm A) or standard best supportive care followed by 2nd-line Nivo at disease progression (Arm B). In both arms, Nivo was administered at the dose of 240 mg i.v. every 2 weeks until progressive disease, intolerable toxicity, or for a maximum of 2 years. The primary endpoint was OS.</p><p><strong>Results: </strong>From Sep 2017 to Aug 2020 125 patients (62 Arm A vs 63 Arm B) were randomized from 32 Italian centers. Accrual was stopped early, before the planned sample size (388 pts) was reached, because of registration of ICPIs in 1st-line. Most patients were male (79.2 %), current/former smokers (93.6 %), had stage IV (74.4 %), performance status 0-1 (98.4 %). mOS (95 % CI) was 14.9 (10.4-18.6) months in arm A vs 18.8 (14.4-21.1) months in arm B (HR 1.09, 95 %CI 0.74-1.62, p = 0.659).</p><p><strong>Conclusions: </strong>In advanced Sq-NSCLC, the use of Nivo as switch maintenance after 1st-line CHT, does not improve OS compared to its use as 2nd-line. Although the optimal use of ICPIs remains in 1st-line, its role as maintenance has to be better investigated.</p><p><strong>Clinicaltrials: </strong>gov: registration number: NCT03542461.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108059"},"PeriodicalIF":4.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864308","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":"An international and multidisciplinary EORTC survey on resectability of stage III non-small cell lung cancer.","authors":"Ilias Houda, Idris Bahce, Chris Dickhoff, Tiuri E Kroese, Stephanie G C Kroeze, Alessio V Mariolo, Marco Tagliamento, Laura Moliner, Mariana Brandão, Yassin Pretzenbacher, John Edwards, Isabelle Opitz, Alessandro Brunelli, Matthias Guckenberger, Paul E van Schil, Sanjay Popat, Torsten Blum, Corinne Faivre-Finn, Dirk de Ruysscher, Jordi Remon, Thierry Berghmans, Anne-Marie C Dingemans, Benjamin Besse, Lizza E L Hendriks","doi":"10.1016/j.lungcan.2024.108061","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108061","url":null,"abstract":"<p><strong>Introduction: </strong>The EORTC-Lung Cancer Group initiated a Delphi consensus process to establish a consensual definition of resectable stage III non-small cell lung cancer (NSCLC) for the use in clinical trials, including a systematic review, survey, and review of clinical cases. Here, the survey results are presented, aimed to identify areas of controversy.</p><p><strong>Methods: </strong>A survey was distributed among the members of six international organizations related to lung cancer. Respondents were interrogated on the resectability (not limited to the technical resectability) of all stage III NSCLC TNM-subsets (8th edition). Additionally, four N2-subdivisions were used. The threshold for agreement was 75%. Answers with \"yes\" were considered upfront resectable. \"Yes\" and \"maybe\" were grouped together and considered potentially resectable. Answers with \"no\" were considered unresectable.</p><p><strong>Results: </strong>558 responses were collected from thoracic surgeons (38%), radiation oncologists (27%), medical oncologists (17%), pulmonologists (14%), and others (4%). Most worked in a specialized center (80%), had >5 years of experience (80%), were European (76%), male (73%), and treated >20 patients with stage III NSCLC annually (77%). Agreement was found in 26 (70%) out of 37 TNM-subsets: 9 (24%) were considered (potentially) resectable, and 17 (46%) unresectable. There was no agreement for 11 (30%) TNM-subsets: smaller tumors with N2-multistation, larger tumors with N2-single station, and invasive T4-tumors with maximum N2-single station involvement.</p><p><strong>Conclusions: </strong>This international and multidisciplinary survey showed agreement on the resectability for the majority of stage III NSCLC TNM-subsets, but also identified several TNM-subsets for which no agreement was found.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108061"},"PeriodicalIF":4.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872497","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 DETECTION project part 1: An international Delphi survey about diagnostics and treatment of anterior mediastinal cystic lesions.","authors":"Florit Marcuse, Daphne Dumoulin, Koen Hartemink, Monique Hochstenbag, Sjaak Burgers, Hester A Gietema, Ties A Mulders, Elvin Eryigit, Jos Maessen, Lex Maat, Myrurgia Abdul Hamid, Jan von der Thüsen, Kim Monkhorst, Anne-Marie C Dingemans, Nicolas Girard","doi":"10.1016/j.lungcan.2024.108055","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108055","url":null,"abstract":"<p><strong>Background: </strong>Differentiating benign anterior mediastinal cysts from malignancies is challenging in clinical practice. International guidelines on optimal diagnostics and treatment for anterior mediastinal cystic lesions are lacking. The first part of the DETECTION project focuses on possible heterogeneity in diagnostics and treatment of anterior mediastinal cystic lesions among international thoracic medical experts.</p><p><strong>Methods: </strong>A Delphi-survey was created by 14 multidisciplinary panel members, affiliated with three Dutch tertiary referral hospitals for thymic tumours. The survey contained 55 questions and was reviewed by international experts of the International Thymic Malignancy Interest Group (ITMIG) and Réseau tumeurs THYMiques et Cancer (RYTHMIC). The survey was launched online for members of the ITMIG and RYTHMIC from May 26th, 2023 till July 18th, 2023.</p><p><strong>Results: </strong>The survey was completed by 21 thoracic surgeons, 15 radiologists, 15 medical oncologists, 11 pathologists, 9 pulmonologists, and 4 radiation oncologists from 24 countries. Heterogeneity was observed in performed diagnostic radiological imaging, laboratory tests, indications for surgery and follow-up of anterior mediastinal cysts. Cystic wall thickness of anterior mediastinal cysts was reported as clinical relevant in decision making more frequently by thoracic surgeons (76.2 %) than pulmonologists (44.4 %) and medical oncologists (15.4 %) (p = 0.015).</p><p><strong>Conclusions: </strong>The survey outcomes showed heterogeneity in the diagnostics and indication for resection of anterior mediastinal cysts among thoracic medical experts. A large variation in radiological imaging, laboratory tests, surgery, pathological analyses, and follow-up of anterior mediastinal cysts was observed. The development of evidence-based clinical practice guidelines may guide clinicians.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108055"},"PeriodicalIF":4.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807507","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":"Long-term outcome of chemoimmunotherapy for extensive-stage small-cell lung cancer according to key clinical trial eligibility: 3-year outcomes from a prospective cohort study.","authors":"Jun Sugisaka, Daichi Fujimoto, Motohiro Tamiya, Akito Hata, Hirotaka Matsumoto, Toshihide Yokoyama, Yoshihiko Taniguchi, Junji Uchida, Yuki Sato, Takashi Kijima, Hisashi Tanaka, Naoki Furuya, Takeshi Masuda, Yoshihiko Sakata, Eisaku Miyauchi, Go Saito, Satoru Miura, Teppei Yamaguchi, Haruko Daga, Shinya Sakata, Nobuyuki Yamamoto, Hiroaki Akamatsu","doi":"10.1016/j.lungcan.2024.108056","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108056","url":null,"abstract":"<p><strong>Background: </strong>Chemoimmunotherapy is the standard first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC); however, its real-world long-term outcomes associated with patient backgrounds are still unclear. We explored this association using an updated large real-world prospective cohort with a minimum follow-up of 3 years.</p><p><strong>Methods: </strong>This prospective cohort study, conducted across 32 hospitals, enrolled patients with ES-SCLC receiving carboplatin, etoposide, and atezolizumab between September 1, 2019 and September 30, 2020. Updated data with a minimum 3-year follow-up period were analyzed. Patients who met eligibility criteria for pivotal phase 3 clinical trials were considered \"trial-eligible.\"</p><p><strong>Results: </strong>The median (range) time from the treatment initiation to data cutoff (September 30, 2023) was 42.2 (35.8-48.2) months for the enrolled 207 patients. Most patients (89 %) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients fulfilling the inclusion criteria (132 [64 %]) were categorized as trial-eligible. The 3-year progression-free survival (PFS) probability and overall survival (OS) were 6.1 % and 20.9 %, respectively. The 3-year OS probabilities for trial-eligible and trial-ineligible patients were 26.7 and 9.5 %, respectively. The trial-eligible cohort had a larger percentage of patients achieving a 3-year OS (30/132, 22.7 %) than the trial-ineligible cohort (5/75, 6.7 %) (P = 0.003) CONCLUSIONS: Our study provides the first documentation of the long-term outcomes following chemoimmunotherapy in a large prospective real-world cohort of patients with ES-SCLC. Key eligibility criteria significantly influenced the long-term effectiveness. These findings provide valuable insights into the practical effectiveness of chemoimmunotherapy and clinical decision-making for patients with ES-SCLC.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108056"},"PeriodicalIF":4.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824368","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":"Sunvozertinib monotherapy in EGFR tyrosine kinase inhibitor-resistant non-small cell lung cancer with EGFR mutations.","authors":"Mengzhao Wang, Yan Xu, Wen-Tsung Huang, Wu-Chou Su, Bo Gao, Chee Khoon Lee, Jian Fang, Xuehua Zhu, Zhenfan Yang, Pasi A Jänne, James Chih-Hsin Yang","doi":"10.1016/j.lungcan.2024.108053","DOIUrl":"https://doi.org/10.1016/j.lungcan.2024.108053","url":null,"abstract":"<p><strong>Background: </strong>Multiple agents can be used to treat patients with EGFR mutated non-small cell lung cancer (NSCLC) who develop resistance to EGFR tyrosine kinase inhibitors (TKIs), but the clinical outcome was not satisfactory, especially in patients with multiple lines of prior therapies. Therefore, there is an unmet medical need for these patients. Sunvozertinib is an oral, potent, irreversible, and mutant-selective EGFR TKI targeting EGFR mutations with weak activity against wild-type EGFR. We investigated the efficacy and safety of sunvozertinib monotherapy in treating EGFR TKI-resistant patients with NSCLC harboring EGFR mutations.</p><p><strong>Methods: </strong>This was a pooled analysis of phase 1 and 2 studies (WU-KONG1, WU-KONG2 and WU-KONG15). Eligible patients received sunvozertinib at doses ranging from 50 mg to 400 mg once daily. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and progression free survival (PFS). Safety endpoints included adverse events and serious adverse events. In addition, plasma specimens were collected at baseline to assess EGFR mutation types and genetic alterations in EGFR downstream signaling pathway.</p><p><strong>Results: </strong>Forty patients were enrolled. Ninety percent received ≥ 3 prior lines of therapies. The best ORR was 27.5 %, and DCR was 60 %. The median DoR and PFS were 6.5 months and 6 months, respectively. Higher ORR was seen in patients whose last line of treatment was chemotherapy rather than EGFR TKI (31.6 % vs. 14.3 %). Greater responses were seen in patients with EGFR sensitizing and T790M double mutations (ORR: 55.6 %). The safety profile of sunvozertinib was consistent with previous reports.</p><p><strong>Conclusions: </strong>Sunvozertinib has promising activity implying future investigations in the patients with EGFR mutated NSCLC who developed resistance to prior EGFR TKI.</p>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"108053"},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794993","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":"Real-world efficacy of the dabrafenib-trametinib (D-T) combination in BRAF V600E-mutated metastatic non-small cell lung cancer (NSCLC): Results from the IFCT-2004 BLaDE cohort","authors":"Aurélie Swalduz ,&nbsp;Michèle Beau-Faller ,&nbsp;David Planchard ,&nbsp;Julien Mazieres ,&nbsp;Sophie Bayle-Bleuez ,&nbsp;Didier Debieuvre ,&nbsp;Vincent Fallet ,&nbsp;Margaux Geier ,&nbsp;Alexis Cortot ,&nbsp;Sébastien Couraud ,&nbsp;Catherine Daniel ,&nbsp;Charlotte Domblides ,&nbsp;Eric Pichon ,&nbsp;Elizabeth Fabre ,&nbsp;Sébastien Larivé ,&nbsp;Ulrike Lerolle ,&nbsp;Pascale Tomasini ,&nbsp;Marie Wislez ,&nbsp;Pascale Missy ,&nbsp;Franck Morin ,&nbsp;Jean-Bernard Auliac","doi":"10.1016/j.lungcan.2024.108038","DOIUrl":"10.1016/j.lungcan.2024.108038","url":null,"abstract":"<div><h3>Background</h3><div>BRAF V600E mutations occur in 2–5 % of advanced non-small cell lung cancer (NSCLC) patients. The dabrafenib-trametinib (D-T) combination was associated with improved and durable OS in patients in phase II. This study (IFCT-2004 BLaDE study) reported the efficacy of D-T combination in a large retrospective French real-world multicenter cohort of patients with advanced BRAF V600E-mutated NSCLC.</div></div><div><h3>Method</h3><div>Patients with advanced BRAF V600E-mutated NSCLC diagnosed between 01.01.2016 and 31.12.2019 and treated with D-T in combination, regardless of the treatment line, were included. The primary endpoint was the 12-month OS rate (%) in patients receiving D-T as a second-line therapy or beyond.</div></div><div><h3>Results</h3><div>A total of 163 patients were included: 50.3 % were female, 30.2 % were never smokers, 95.1 % had adenocarcinoma, and 78.2 % had a PDL1 ≥ 1 %. The median age was 68.3 years. At D-T initiation, 80.8 % of patients had a PS of 0/1, 78.6 % had stage IV disease, and 20.9 % had brain metastasis. At the cutoff, the median follow-up was 27.4 months. The 12-month OS rate in patients receiving D + T as a second-line therapy or beyond (n = 119) was 67.4 %, with a median progression-free survival (mPFS) of 10.4 months. Among the 44 patients who received D + T as a first-line therapy, the 12-month OS rate was 67.4 %, with an mPFS of 18.2 months. D-T discontinuation for toxicity was reported in 10.3 % of patients.</div></div><div><h3>Conclusions</h3><div>To our knowledge, this is the largest retrospective cohort of <em>BRAF-</em>mutated patients reported. The findings confirmed the significant efficacy of D-T in combination with BRAF V600E-mutated metastatic NSCLC in pretreated and untreated patients. These results under real-world conditions are consistent with those of other registered studies.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"199 ","pages":"Article 108038"},"PeriodicalIF":4.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747220","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}