Lung Cancer: Targets and Therapy最新文献

{"title":"Emerging Targets in Non-Small Cell Lung Cancer.","authors":"Jing Wang, Layana Biglow, Megan Baumgart","doi":"10.2147/LCTT.S511767","DOIUrl":"10.2147/LCTT.S511767","url":null,"abstract":"<p><p>The identification of molecular driver mutations in non-small cell lung cancer (NSCLC) has changed the therapeutic landscape for this disease. Over the last 20 years, a growing number of driver mutations have been identified in addition to new targeted therapies that have resulted in significant improvement in survival for a subset of patients. There is ongoing research to identify additional molecular targets and therapeutic strategies to improve outcomes in a greater percentage of patients with lung cancer. This review aims to highlight new therapeutic strategies targeting known driver mutations and data regarding emerging molecular targets for the treatment of NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"115-124"},"PeriodicalIF":3.3,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alectinib Efficacy Post-Brigatinib Against Advanced <i>ALK</i>+ Non-Small Cell Lung Cancer (BrigALK2-GFPC 02-2019 Study).","authors":"Renaud Descourt, Florian Guisier, Maurice Pérol, Jacques Cadranel, Helene Doubre, Michael Duruisseaux, Stéphane Culine, Bertrand Mennecier, Olivier Bylicki, Christos Chouaid, Laurent Greillier","doi":"10.2147/LCTT.S522038","DOIUrl":"10.2147/LCTT.S522038","url":null,"abstract":"<p><strong>Background: </strong>Brigatinib and alectinib are next-generation anaplastic lymphoma kinase inhibitors (ALKis) showing efficacy against naïve and post-crizotinib-treated advanced <i>ALK</i>+ non-small-cell lung cancers (NSCLCs). Real-world data on alectinib efficacy after brigatinib failure are lacking.</p><p><strong>Methods: </strong>Alectinib efficacy was retrospectively assessed in patients previously treated with brigatinib during an early-access program (EAP) from 1 August 2016 to 21 January 2019. The primary endpoint was alectinib median progression-free survival (mPFS) according to local investigators.</p><p><strong>Results: </strong>Among the 183 patients included in the brigatinib EAP, 92 (50.3%) received ≥1 agent(s) post-brigatinib; 30 (16.4%) received alectinib, 19 (10.4%) immediately post-brigatinib; 11 (6%) after ≥1 other treatment line(s). With median follow-up at 25.5 (95% CI: 10.6-30.5) months, mPFS on brigatinib for the study population (n = 30) was 13.6 (95% CI: 6.3-17.7) months. For patients given alectinib immediately post-brigatinib, mPFS and median overall survival (mOS) were 4.8 (95% CI: 2.0-12.5) and 27 (95% CI: 12.5-not reached (NR)) months, respectively. In this subgroup, brigatinib was discontinued for toxicity or progression for 5/19 (26%) or 14/19 (74%) patients, with mPFS lasting 12.5 (95% CI: 3.3-17.9 and 3.4 (95% CI: 0.9-9.2) months, respectively. For patients receiving ≥1 agent(s) between brigatinib and alectinib, with median follow-up at 13.3 (95% CI: 2.3-31.5) months, mPFS and mOS were 5.0 (95% CI: 0.5-18.8) and 19 (95% CI: 2.3-NR) months, respectively.</p><p><strong>Conclusion: </strong>According to the results of this retrospective real-world study, alectinib post-brigatinib showed limited overall activity but remains an option for patients with advanced <i>ALK</i>+ NSCLCs, especially when brigatinib was discontinued because of toxicity.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"107-114"},"PeriodicalIF":3.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidermal Growth Factor Receptor Kinase Domain Duplication in Lung Adenocarcinoma with Sensitive Response to Afatinib: A Case Report and Literature Review.","authors":"Shuangru Chen, Liting Zhang, Jun Wang, Jiayao Lu, Ye Chen, Mingzhu Ling","doi":"10.2147/LCTT.S532278","DOIUrl":"10.2147/LCTT.S532278","url":null,"abstract":"<p><p>Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare form of EGFR mutation. Unlike the classical mutations such as exon 19 deletion and exon 21 p.L858R point mutation, EGFR-KDD is a special type of large genomic rearrangement (LGR) that results in the duplication of the tyrosine kinase domain at the protein level, leading to the formation of an intramolecular dimer and activation of the EGFR signaling pathway. Case reports and in vitro experiments have shown that EGFR-KDD patients can benefit from EGFR TKI treatment. Similar to classical EGFR mutations, EGFR-KDD inevitably develops resistance during EGFR TKI treatment, leading to disease progression. Due to the rarity of EGFR-KDD, the acquired resistance mechanisms are not yet fully understood, but known mechanisms include EGFR amplification and T790M mutation. In this study, we report a 71-year-old female EGFR-KDD patient who showed a positive response to afatinib treatment initially, but developed resistance upon tumor progression. Subsequent next-generation sequencing (NGS) on the re-biopsy revealed TP53 exon c.688_764 deletion and MET exon 15-20 duplication, suggesting that MET bypass activation might be the acquired resistance mechanisms. Additionally, we conducted a literature review on EGFR-KDD and examined case reports of EGFR-KDD patients treated with EGFR TKIs to summarize the treatment outcomes and resistance mechanisms. We hope to provide more treatment information for patients with rare gene mutations in lung cancer.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"97-105"},"PeriodicalIF":3.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and Transcriptomic Profiles in Smokers and Never-Smokers Lung Squamous Cell Carcinoma Patients.","authors":"Matteo Canale, Alessandra Virga, Davide Angeli, Eugenio Fonzi, Letizia Gnetti, Alessandra Dubini, Gianluca Tedaldi, Milena Urbini, Giovanni Bocchialini, Elisabetta Petracci, Alberto Verlicchi, Paola Cravero, Fabrizio Citarella, Chiara Bennati, Kalliopi Andrikou, Angelo Delmonte, Lucio Crinò, Paolo Carbognani, Paola Ulivi, Luca Ampollini","doi":"10.2147/LCTT.S517580","DOIUrl":"10.2147/LCTT.S517580","url":null,"abstract":"<p><strong>Purpose: </strong>Lung Squamous Cell Carcinoma (SCC) is a Non-Small Cell Lung Cancer (NSCLC) subtype with a strong clinical association with smoking habits and a very low incidence in never-smokers. Molecular profiling of SCC in never-smokers could unveil tumor vulnerabilities and new treatment strategies.</p><p><strong>Patients and methods: </strong>We considered a patient cohort of 17 former or current smokers (51.5%) and 16 never-smoker SCC patients (48.5%). TruSight Oncology^® 500, investigating hotspots in 523 cancer-related genes, Tumor mutation burden (TMB) and microsatellite instability (MSI), and RNA sequencing was performed on tumor tissue. Genomic and transcriptomic profiles were compared between smokers and never-smoker patients.</p><p><strong>Results: </strong>The most frequently altered genes were <i>TP53</i> (67%), <i>CDKN2A</i> (20%) and <i>PIK3CA</i> (17%), with no substantial differences between groups, except for <i>TP53</i> which was more frequently mutated in smokers (86.7% vs 46.7%, p = 0.05), who also showed a higher TMB with respect to non-smokers (median 11 mut/Mb vs 5.5 mut/Mb, p = 0.028); all patients were stable for MSI score (median 1.87 vs 1.82, p = 0.87). Activating mutations in <i>EGFR</i> and <i>MET</i> were found in one and two never-smokers, respectively. Three smoker patients had simultaneous amplifications in <i>FGF3, FGF19</i> and <i>FGF4</i>. Enrichment analyses showed that cyclin-dependent protein Ser/Thr kinase activity and PI3K signaling pathways were affected in both groups, while cellular damage response was exclusively altered in never-smokers. Unsupervised hierarchical clustering on transcriptomes effectively identified different specific transcriptional subtypes between smokers and never-smokers. Gene set enrichment analysis highlighted that tumors from never-smokers are characterized by dysregulation in cell membrane potential and ion homeostasis across cell membrane pathways.</p><p><strong>Conclusion: </strong>Genomic and transcriptomic profiles deeply differentiate SCC occurring in never-smokers with respect to SCC in smoker patients. Moreover, SCC could carry canonical NSCLC) activating mutations. Our data suggest that deep molecular analyses resolve tumor heterogeneity and may help with new algorithm-based treatment strategies for SCC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"85-96"},"PeriodicalIF":5.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Effectiveness and Safety Profile of First-Line Immune Checkpoint Inhibitors Combined with Chemotherapy in Pulmonary Sarcomatoid Carcinoma.","authors":"He Du, Xinyu Song, Fengying Wu","doi":"10.2147/LCTT.S494990","DOIUrl":"10.2147/LCTT.S494990","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary sarcomatoid carcinoma (PSC) represents a rare subtype of non-small cell lung cancer (NSCLC), and it has poor pathologic differentiation, aggressive progression, and early metastasis. Conventional antitumor therapies demonstrate limited efficacy against PSC, which is frequently associated with unfavorable clinical outcomes.</p><p><strong>Methods: </strong>We conducted an open-label, single-arm Phase II trial. This study has been registered with Clinical Trials (ChiCTR2000031478). Patients received immune checkpoint inhibitor (ICI) combination with chemotherapy, the treatment continued until disease progression, unacceptable toxicity, patient withdrawal, or death. The primary endpoint was objective response rate (ORR), with secondary endpoints comprising progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and treatment-emergent adverse events.</p><p><strong>Results: </strong>From March 2021 through August 2023, a total of 38 patients were enrolled. The study comprised predominantly male participants (91%, n=34) with a median age of 65.4 years. Notably, 86.8% (n=33) had smoking histories. The ORR and DCR were 73.7% and 94.7%, respectively. The median PFS was 13.3 months (95% CI, 10.2-15.7) and median OS was not reached. The most common immune-related adverse events were pneumonitis, the incidence of which was 13.2%. The majority of observed AEs were grades 1 or 2 and all AEs were manageable. Only two patients discontinued treatment due to grade 3 immune-related pneumonitis during the study.</p><p><strong>Conclusion: </strong>In our trial, we found that ICI combination with chemotherapy showed robust efficacy alongside acceptable toxicity in advanced-stage PSC. Taken together, ICI combination with chemotherapy could be a better option for PSC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"73-83"},"PeriodicalIF":5.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Role of FASN in Lung Cancer Stem Cells in Sensitive and Resistant EGFR-Mutated Non-Small Cell Lung Cancer Cells.","authors":"Emma Polonio-Alcalá, Sira Ausellé-Bosch, Gerard Riesco-Llach, Pablo Novales, Lidia Feliu, Marta Planas, Joaquim Ciurana, Teresa Puig","doi":"10.2147/LCTT.S512936","DOIUrl":"10.2147/LCTT.S512936","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer stem cells (CSCs) drive tumor initiation, relapse, and metastasis. Our research team developed polycaprolactone electrospun (PCL-ES) scaffolds for enriching lung CSCs (LCSCs) since monolayer culture do not allow the study of this malignant population. The upregulation of fatty acid synthase (FASN) correlates with resistance to tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR), and its inhibition induces cytotoxicity in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) cells. Therefore, this study aims to elucidate the role of FASN and related signaling pathways in LCSCs cultured in PCL-ES scaffolds and to evaluate the effectiveness of FASN inhibitor G28, a synthetic derivative of (-)-epigallocatechin-3-gallate (EGCG), against this population.</p><p><strong>Methods: </strong>EGFR-TKI-sensitive and -resistant cell modes were used. FASN expression and function were studied by RT-qPCR, Western blotting, and free fatty acid quantification, while related signaling pathways (EGFR, MAPK, AKT, and STAT3) were examined by Western blotting. The effects of G28 on LCSCs -including its impact on FASN and related signaling-were evaluated using the MTT assay and Western blotting.</p><p><strong>Results: </strong>LCSCs cultured in PCL-ES scaffolds showed a significant FASN upregulation, supporting their proliferation and maintenance. Despite reduced EGFR activation in 3D-cultured cells, downstream signaling responses differed: PC9 cells exhibited higher levels of p-AKT, p-MAPK, and p-STAT3, while PC9-GR3 cells showed reduced p-MAPK and p-AKT, with no changes in p-STAT3. Regarding G28 treatment, it exhibited cytotoxic effects in both 2D- and 3D-cultured cells, suggesting potential efficacy in targeting both non-LCSCs and LCSCs. Furthermore, the treatment downregulated FASN and AKT, reducing or avoiding the proliferation of this malignant population.</p><p><strong>Conclusion: </strong>Our results highlight the potential of G28 as a therapeutic option for targeting LCSCs in both sensitive and resistant EGFRm NSCLC cells, though additional studies are required to validate these results and assess their clinical applicability.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"57-72"},"PeriodicalIF":5.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LAURA Completes the Osimertinib Treatment Jigsaw Puzzle of <i>EGFR</i>+ NSCLC from Stage IB to IV: Adjuvant Osimertinib Significantly Improves PFS and CNS Progression in Unresectable Stage III <i>EGFR</i>-Mutated NSCLC Compared to Placebo (LAURA, NCT03521154).","authors":"Faustine X Luo, Zhaohui Arter, Sai-Hong Ignatius Ou, Misako Nagasaka","doi":"10.2147/LCTT.S520833","DOIUrl":"https://doi.org/10.2147/LCTT.S520833","url":null,"abstract":"<p><p>The current standard of care for unresectable stage III non-small cell lung cancer (NSCLC) involves a concurrent platinum-based doublet chemotherapy and chest radiotherapy, followed by consolidative therapy with durvalumab, an anti-programmed death ligand 1 (PD-L1) antibody, based on the PACIFIC trial (NCT02125461). However, the utility of durvalumab in <i>EGFR</i>-mutated lung cancer patients is questionable based on post-hoc analysis and multi-institutional retrospective analysis. Osimertinib is a third-generation <i>EGFR</i>-tyrosine kinase inhibitor (TKI) with proven clinical efficacy in NSCLC. Given that durvalumab showed no benefit in unresectable Stage III <i>EGFR</i>-mutated NSCLC, it is exciting that most recently, the LAURA trial has demonstrated promising outcomes with adjuvant osimertinib in unresectable, stage III <i>EGFR</i>-mutated NSCLC after definitive chemoradiotherapy with significant improvement in PFS compared to placebo. Furthermore, the LAURA trial demonstrates that osimertinib has a protective effect against distant metastases and CNS progression in this patient population. Here, we explore the results of the LAURA trial and how it transforms the standard-of-care treatment for patients with unresectable, stage III <i>EGFR</i>-mutated NSCLC moving forward.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"51-55"},"PeriodicalIF":5.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of <i>EGFR</i> Mutations in Vietnamese Patients with Resected Early Stage Non-Small Cell Lung Cancer: EARLY-EGFR Study.","authors":"Tu Van Dao, Van Luong Dinh, Thanh Vinh Doan, Tri Le Phuong","doi":"10.2147/LCTT.S494554","DOIUrl":"https://doi.org/10.2147/LCTT.S494554","url":null,"abstract":"<p><strong>Introduction: </strong>Comprehensive profiling of mutations in the <i>EGFR</i> gene is vital for selecting patients eligible for <i>EGFR</i> targeted therapies.</p><p><strong>Methods: </strong>We investigated the prevalence of <i>EGFR</i> mutations and treatment patterns in patients with early stage non-small cell lung cancer (NSCLC) in Vietnam as a part of EARLY-EGFR (Clinical Trial Identifier: NCT04742192), a global, real-world study. Consecutive patients with surgically resected stage IA-IIIB, non-squamous NSCLC were diagnosed from August 2021 to June 2022 and were prospectively enrolled from November 2021 to July 2022.</p><p><strong>Results: </strong>A total 200 patients (age: median [range], 60.0 [30.0-80.0] years) were enrolled from 3 centers; 56.0% were males and 64.0% never smoked. The prevalence of <i>EGFR</i> mutations was 51.0% (102/200) including deletions in <i>exon-19</i> (49.0%) and <i>exon-21 L858R</i> mutations (33.3%). Females (73.9%, 65/88), patients aged ≥60 years (52.5%, 53/101), nonsmokers (61.2%, 63/103) and those with stage I (55.8%, 67/120) had higher prevalence of <i>EGFR</i> mutations. Multivariate analysis (adjusted odds ratio [aOR]) showed <i>EGFR</i> mutations to be significantly associated (p < 0.05) with female gender (aOR = 5.90), age ≥60 years (aOR = 1.05), and stage III disease (vs stage I) (aOR = 0.30).</p><p><strong>Conclusion: </strong>These results underscore the need for <i>EGFR</i> testing early in management algorithm of NSCLC in Vietnam to identify patients eligible for targeted therapy in concordance with international guidelines.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"39-49"},"PeriodicalIF":5.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12025828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Subsequent Treatment on Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer Transformed to Small-Cell Lung Cancer.","authors":"Ching-Yi Chen, How-Wen Ko, Po-Wei Hu, Cheng-Yu Chang, Chung-Yu Chen, Shih-Chieh Chang, Yu-Chi Chiu, Yu-Feng Wei","doi":"10.2147/LCTT.S516527","DOIUrl":"https://doi.org/10.2147/LCTT.S516527","url":null,"abstract":"<p><strong>Purpose: </strong>In epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs), transformation to small-cell lung cancer (SCLC) is associated with poor outcomes, and the optimal treatment strategy is unclear. This study aimed to investigate the clinical factors and treatments associated with outcomes in this group.</p><p><strong>Patients and methods: </strong>This retrospective multicenter study enrolled patients with SCLC transformed from advanced NSCLC after progression on EGFR-TKI treatment. We analyzed clinical and demographic characteristics, first-line EGFR-TKI treatments, and subsequent regimens to identify factors associated with clinical outcomes.</p><p><strong>Results: </strong>Twenty-seven patients diagnosed with SCLC transformation after EGFR-TKI therapy between 2018 and 2023 were enrolled, most of whom had an EGFR exon 19 deletion (67%). The subsequent treatment regimens included traditional chemotherapy (CT) in 12 patients (44%), combined CT/EGFR-TKI in 10 patients (37%), and combined CT/immunotherapy in 5 patients (19%). The median progression-free survival (PFS) with first-line EGFR-TKI treatment, subsequent SCLC treatment, and overall survival (OS) were 16.1 months, 6.4 months, and 39.5 months, respectively. The overall response rate (ORR), disease control rate (DCR), and median PFS for subsequent treatments were 38.5%, 69.2%, and 6.4 months, respectively. The DCRs for subsequent CT, CT/TKI, and CT/immunotherapy were 41.7%, 88.9%, and 100%, respectively. ORR and PFS were higher in the CT/TKI (44.4% and 7.2 months) and CT/immunotherapy (80.0% and 11.3 months) groups compared to CT (16.7% and 3.7 months), but these differences were not statistically significant. Univariate and multivariate analyses showed no significant differences in PFS and OS among treatments.</p><p><strong>Conclusion: </strong>In patients with SCLC transformed from advanced NSCLC after EGFR-TKI treatment, adding immunotherapy and EGFR-TKI to CT improved DCR and showed trends in ORR and PFS, but did not provide an OS benefit. More prospective studies with varied therapeutic approaches are needed to confirm these findings.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"25-37"},"PeriodicalIF":5.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Profiling of Extensive Stage Small-Cell Lung Cancer Patients Identifies Molecular Factors Associated with Survival.","authors":"Matteo Canale, Milena Urbini, Elisabetta Petracci, Davide Angeli, Gianluca Tedaldi, Ilaria Priano, Paola Cravero, Michele Flospergher, Kalliopi Andrikou, Chiara Bennati, Davide Tassinari, Alessandra Dubini, Giulio Rossi, Riccardo Panzacchi, Mirca Valli, Giuseppe Bronte, Lucio Crinò, Angelo Delmonte, Paola Ulivi","doi":"10.2147/LCTT.S492825","DOIUrl":"10.2147/LCTT.S492825","url":null,"abstract":"<p><strong>Objective: </strong>Extensive stage Small-Cell Lung Cancer (ES-SCLC) is the most lethal lung cancer, and the addition of immunotherapy conferred a slight survival benefit for patients. Extensive molecular profiling of patients treated with chemotherapy (CT) or chemotherapy plus immunotherapy (CT+IO) would be able to identify molecular factors associated with patients' survival.</p><p><strong>Material and methods: </strong>In this retrospective study, 99 ES-SCLC patients were considered. Of the 79 includible patients, 42 received CT (median age 71 y/o, I-IIIQ: 65-76), and 37 received CT+IO (median age 71 y/o, I-IIIQ 66-75). The FoundationOne CDx assay was performed on patients' tumor tissues.</p><p><strong>Results: </strong>The most mutated genes were <i>TP53</i> (99%), <i>RB1</i> (78%), <i>PTEN</i> (23%) and <i>MLL2</i> (20%), with no significant differences between the treatment groups. As a continuous variable, Tumor Mutation Burden (TMB) had an effect on patients' progression-free survival (PFS) by type of treatment (HR 1.81 (95%, CI: 0.99-3.31) and HR 0.84 (95%, CI: 0.56-1.26) for patients treated with CT and CT+IO, respectively). TMB was also computed and dichotomized using two different cut-offs: considering cut-offs of 10 mut/Mb and >16 mut/Mb, 45 patients (57%) and 68 patients (86.1%) had a low TMB, respectively. A high TMB (cut-off 10 mut/Mb) predicted worse PFS in patients treated with CT (<i>p</i>=0.046); even though not statistically significant, a high TMB (cut-off 16 mut/Mb) predicted a better survival in patients treated with CT+IO. Moreover, at univariate analysis, <i>MLL2</i> mutations were associated with better prognosis in the overall case series (HR_PFS = 0.51, 95% CI: 0.28-0.94), and overall survival (HR_OS = 0.52, 95% CI: 0.28-0.97).</p><p><strong>Conclusion: </strong>In ES-SCLC, TMB is associated with worse survival in patients treated with CT alone, and with better survival in patients treated with CT+IO, whether considered as a continuous or a dichotomized variable, at different cut-offs. Alterations in epigenetic factors are also associated to better patient prognosis.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"16 ","pages":"11-23"},"PeriodicalIF":5.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}