Lung Cancer最新文献

{"title":"Comparative efficacy and safety of post-TKI treatments for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and network meta-analysis","authors":"Yuanyuan Wang ,&nbsp;Lin Zhang ,&nbsp;Jianhua Zhan ,&nbsp;Ling Wen ,&nbsp;Xinyuan Zhao ,&nbsp;Haishuang Sun ,&nbsp;Xueyuan Chen ,&nbsp;Yaxiong Zhang ,&nbsp;Gang Chen ,&nbsp;Yuanyuan Zhao ,&nbsp;Yan Huang ,&nbsp;Wenfeng Fang ,&nbsp;Li Zhang ,&nbsp;Dongchen Sun ,&nbsp;Yunpeng Yang","doi":"10.1016/j.lungcan.2026.108914","DOIUrl":"10.1016/j.lungcan.2026.108914","url":null,"abstract":"<div><h3>Background</h3><div>Despite the availability of several validated therapies, the optimal second-line regimen for <em>EGFR</em>-mutant non-small cell lung cancer (NSCLC) after tyrosine kinase inhibitor (TKI) failure remains uncertain.</div></div><div><h3>Methods</h3><div>The protocol was registered in PROSPERO (CRD420251157131). We systematically searched MEDLINE, Embase, CENTRAL, and conference proceedings (to Oct 20, 2025) for phase III randomized controlled trials (RCTs). A Bayesian network <em>meta</em>-analysis was performed. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS) and the incidence of grade ≥3 treatment-related adverse events (TRAEs).</div></div><div><h3>Results</h3><div>Eleven RCTs (3,650 patients, seven regimens) were included. Compared to chemotherapy, sacituzumab tirumotecan (SacTMT), amivantamab plus chemotherapy (Chemo-Ami), and chemo-immunotherapy plus anti-angiogenic agent (Chemo-IO-anti-VEGF) demonstrated superior PFS (HR 0.49, 0.48, 0.53, respectively) and OS (HR 0.60, 0.73, 0.83, respectively). SacTMT also significantly improved OS over chemo-immunotherapy (HR 0.68, 95 % CrI 0.48 to 0.95). Regarding safety, Chemo-Ami carried higher grade ≥3 TRAEs risk (OR 2.83, 95 % CrI 1.01 to 7.90) versus chemotherapy, while SacTMT and Chemo-IO-anti-VEGF demonstrated toxicity comparable to chemotherapy.</div></div><div><h3>Conclusions</h3><div>SacTMT, Chemo-Ami, and Chemo-IO-anti-VEGF offer superior efficacy over chemotherapy for <em>EGFR</em>-mutant NSCLC after TKI progression. SacTMT and Chemo-IO-anti-VEGF may have more favorable safety profiles than Chemo-Ami. This comparative evidence helps to inform clinical decision-making.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108914"},"PeriodicalIF":4.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927316","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":"Letter to the editor: treatment sequencing in synchronous oligometastatic NSCLC − the need for standardized patient selection Criteria","authors":"Peng Bai ,&nbsp;Jun Zhang","doi":"10.1016/j.lungcan.2026.108911","DOIUrl":"10.1016/j.lungcan.2026.108911","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108911"},"PeriodicalIF":4.4,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927315","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":"Proteomic profiling of early-stage non-small cell lung cancer identifies a high-performance protein signature associated with postoperative recurrence","authors":"Ying Huang ,&nbsp;Qiuhua Deng ,&nbsp;Jie Li ,&nbsp;Runchen Wang ,&nbsp;Zhen Li ,&nbsp;Liping Liu ,&nbsp;Lei Song ,&nbsp;Xiaohong Zhao ,&nbsp;Liyan Huang ,&nbsp;Haihong Yang ,&nbsp;Weiqiang Yin","doi":"10.1016/j.lungcan.2026.108907","DOIUrl":"10.1016/j.lungcan.2026.108907","url":null,"abstract":"<div><h3>Background</h3><div>The 5-year recurrence rate remains significantly high (∼30 %) in patients with early-stage Non-Small Cell Lung Cancer (NSCLC), even after complete tumor resection. Recurrence prediction primarily relies on pathological assessment and genomic abnormalities. However, proteins — the functional executors of genetic information — may offer additional prognostic value. In this study, we aimed to develop a model integrating proteomic and clinical features to improve recurrence prediction in early-stage NSCLC.</div></div><div><h3>Methods</h3><div>We recruited 351 stage Ⅰ NSCLC patients who underwent radical surgery in discovery corhort. An additional 103 participants from external prospective cohort were used for validation. Clinical data and follow-up outcomes were retrospectively collected. Tumor proteomics profiling was performed using liquid chromatography-mass spectrometry (LC-MS/MS). The proteomics data were acquired using a data-independent acquisition mode with a 150-minute gradient method and analyzed against the human UniProt database using DIA-NN (v1.8.1). We assessed the association between proteomic and clinicopathologic factors and disease-free survival (DFS) using Cox proportional hazards regression. A receiver operating characteristic (ROC) curve analysis was used to construct the predictive model.</div></div><div><h3>Results</h3><div>Of the 351 patients analyzed, 4260 differentially expressed proteins (DEPs) were identified as being associated with tumor recurrence. A nine-protein prediction model outperformed the clinicopathologic-based model (AUC, 0.898 vs. 0.742; <em>P</em> &lt; 0.001) in predicting DFS. A combined model incorporating nine proteins and clinicopathological features demonstrated excellent predictive value for 5-year recurrence in the discovery cohort (AUC = 0.896). Nine proteins combined with clinicopathological features showed an AUC of 0.810 in the external validation cohort and an AUC of 0.844 in the combined cohort.</div></div><div><h3>Conclusion</h3><div>Integrating tumor proteomics with clinicopathologic features enhances risk stratification and improves recurrence prediction after surgical resection of early-stage NSCLC. This approach may enable more personalized postoperative management through refined surveillance intervals and potential adjuvant therapies.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108907"},"PeriodicalIF":4.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046900","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":"Survival outcomes of patients with uncommon EGFR mutations in surgically resected lung adenocarcinoma: A multi-institutional real-world database study (CReGYT-01 EGFR study)","authors":"Kazuki Hayasaka ,&nbsp;Mototsugu Shimokawa ,&nbsp;Naoki Haratake ,&nbsp;Hirotsugu Notsuda ,&nbsp;Shinya Katsumata ,&nbsp;Akira Hamada ,&nbsp;Kotaro Nomura ,&nbsp;Kosuke Fujino ,&nbsp;Mao Yoshikawa ,&nbsp;Ken Suzawa ,&nbsp;Kazuhiko Shien ,&nbsp;Kenichi Suda ,&nbsp;Shuta Ohara ,&nbsp;Shota Fukuda ,&nbsp;Ikuhiko Kinoshita ,&nbsp;Shinkichi Takamori ,&nbsp;Satoshi Muto ,&nbsp;Yusuke Takanashi ,&nbsp;Kiyomichi Mizuno ,&nbsp;Takamitsu Hayakawa ,&nbsp;Yoshinori Okada","doi":"10.1016/j.lungcan.2026.108908","DOIUrl":"10.1016/j.lungcan.2026.108908","url":null,"abstract":"<div><h3>Introduction</h3><div>Uncommon epidermal growth factor receptor (EGFR) mutations (UCM) account for approximately 10% of EGFR-mutant lung adenocarcinoma (LUAD) cases; however, their prognostic impact remains unclear. This study aimed to evaluate postoperative outcomes in patients with UCM compared to those with common mutations (CM) using a large multicenter database.</div></div><div><h3>Materials and methods</h3><div>This retrospective study included 1,636 patients with EGFR-mutant LUAD who underwent complete resection between 2015 and 2018 at 21 Japanese institutions. Patients were classified into the CM and UCM groups. Recurrence-free survival (RFS), overall survival (OS), lung cancer-specific survival (LCSS), and survival after recurrence (SAR) were analyzed using univariable and multivariable analyses and the inverse probability of treatment weighting (IPTW) method.</div></div><div><h3>Results</h3><div>Among the patients, 1,441 (88.1%) had CM and 195 (11.9%) had UCM. RFS was comparable between the groups. However, patients with UCM showed significantly shorter OS and LCSS than those with CM (OS: multivariable hazard ratio [HR] 1.538, 95% confidence interval [CI] 1.003–2.359; LCSS: multivariable HR 1.803, 95% CI 1.064–3.056). This trend was consistently validated using IPTW methods. SAR was also significantly shorter in patients with UCM. Subtype-specific analyses revealed that patients with exon 20 insertions (Ex20ins) had a significantly worse prognosis than those with other UCMs.</div></div><div><h3>Conclusion</h3><div>Patients with UCM had significantly worse OS, LCSS, and SAR than those with CM despite similar RFS. These survival disadvantages in UCM were strongly associated with the Ex20ins subtype. These findings highlight the urgent need for novel perioperative treatments for patients with UCM, especially Ex20ins.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108908"},"PeriodicalIF":4.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927806","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":"Lung cancer in women: current evidence and future research priorities","authors":"Monireh Sadat Seyyedsalehi ,&nbsp;Massimiliano Cani ,&nbsp;Qian Wang ,&nbsp;Chitra Thakur ,&nbsp;Umberto Malapelle ,&nbsp;Chung Yin Kong ,&nbsp;Silvia Novello ,&nbsp;Paolo Boffetta","doi":"10.1016/j.lungcan.2025.108905","DOIUrl":"10.1016/j.lungcan.2025.108905","url":null,"abstract":"<div><div>Lung cancer (LC) remains the leading cause of cancer-related mortality among women worldwide. Compared to men, LC in women presents distinct epidemiologic, biological, and clinical characteristics. A large proportion of LC cases in women occur in never-smokers, underscoring the important roles of environmental exposures, genetic susceptibility, and hormonal influences in disease pathogenesis. LC in women also displays unique molecular profiles, with a higher prevalence of actionable alterations such as epidermal growth factor receptor (<em>EGFR</em>) mutations and anaplastic lymphoma kinase (<em>ALK</em>) rearrangements, which inform targeted therapy selection. Despite advances in chemotherapy, targeted agents, and immunotherapy, sex-based differences in treatment efficacy, toxicity, and survivorship persist and remain incompletely understood. Additional barriers, including limited access to LC screening and the underrepresentation of women in clinical trials, further constrain the application of evidence-based interventions for women. This review synthesizes latest evidence on epidemiology, risk factors, molecular features, screening, treatment outcomes, and survivorship challenges in women with LC with a deep focus on novel approaches to overcome current barriers and disparities to improve prevention, early detection, treatment, and long-term survivorship care.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108905"},"PeriodicalIF":4.4,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010182","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":"Multi-omic screening for pleural mesothelioma in Asbestos-Exposed Populations: A literature review and Recommendations","authors":"Kathleen Zwijsen ,&nbsp;Ellen Heirwegh ,&nbsp;Eline Schillebeeckx ,&nbsp;Elly Marcq ,&nbsp;Adrian Covaci ,&nbsp;Ken Op de Beeck ,&nbsp;Jan P. van Meerbeeck ,&nbsp;Jo Raskin ,&nbsp;Annelies Janssens ,&nbsp;Annemiek Snoeckx ,&nbsp;Kevin Lamote","doi":"10.1016/j.lungcan.2025.108893","DOIUrl":"10.1016/j.lungcan.2025.108893","url":null,"abstract":"<div><h3>Objectives</h3><div>Pleural mesothelioma (PM) is an aggressive thoracic cancer related to historical exposure to asbestos fibres. Symptoms often appear at an advanced stage, leading to delayed diagnosis and dismal prognosis. Early diagnosis is thus crucial in improving patient outcome. Current biomarker research for early detection focuses on different −omics research fields (genomics, proteomics, transcriptomics, metabolomics and volatomics), however with no clinically useful result. Moreover, currently no screening program is advocated for asymptomatic individuals with an established asbestos exposure. The aim of this review is to summarise the advances in different −omics fields and to pinpoint state-of-the art biomarkers with the highest potential to serve as primary targets in clinical trials for early PM detection or screening.</div></div><div><h3>Methods</h3><div>A literature search was performed in the databases MEDLINE and Web Of Science. Research articles published before 1 August 2025 were eligible.</div></div><div><h3>Results</h3><div>In total, 63 articles were included in this review, with specific focus on radiomics, genomics, transcriptomics, epigenomics, proteomics, metabolomics, and volatomics. Several research groups have focused on investigating biomarkers or screening techniques for pleural mesothelioma among individuals with a history of asbestos exposure. Notable approaches include using low-dose Computed Tomography, and determining mesothelin levels and micro-RNAs in blood, and volatile organic compounds in exhaled breath.</div></div><div><h3>Discussion</h3><div>Single biomarkers like miRNAs, mesothelin, and VOCs show promise, but further validation is needed in larger cohorts with correct control groups. A multi-omics approach, which integrates biomarker panels from various −omics areas, has the potential to enhance diagnostic accuracy.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108893"},"PeriodicalIF":4.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927314","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":"Corrigendum to “Treatment and outcomes of limited stage small cell lung cancer in the Canadian small cell lung cancer database (CASCADE)” [Lung Cancer 210 (2025) 108840]","authors":"William J. Phillips ,&nbsp;Luna Jia Zhan ,&nbsp;Deepro Chowdhury ,&nbsp;Jeniszka Gill ,&nbsp;Alexander Sun ,&nbsp;Rebekah Rittberg ,&nbsp;Victor Cohen ,&nbsp;Amanda J.W. Gibson ,&nbsp;Michael Yan ,&nbsp;Daniel Liwski ,&nbsp;Saritha Surapaneni ,&nbsp;Marie Frederique D’Amours ,&nbsp;Fabian P.S. Yu ,&nbsp;YongJin Kim ,&nbsp;Rana A. Qadeer ,&nbsp;David E. Dawe ,&nbsp;Jason Agulnik ,&nbsp;Vishal Navani ,&nbsp;Andrea S. Fung ,&nbsp;Stephanie Snow ,&nbsp;Sara Moore","doi":"10.1016/j.lungcan.2025.108875","DOIUrl":"10.1016/j.lungcan.2025.108875","url":null,"abstract":"","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"211 ","pages":"Article 108875"},"PeriodicalIF":4.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775021","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":"Clinical impact of TP53 classifications in previously treated advanced driver-negative non-small cell lung cancer: A biomarker analysis of the OAK and POPLAR randomized clinical trials","authors":"Deborah Di-Xin Zhou ,&nbsp;Sarah J. Lord ,&nbsp;Frank Po-Yen Lin ,&nbsp;Wendy A. Cooper ,&nbsp;Milita Zaheed ,&nbsp;Robert John Simes ,&nbsp;Thomas John ,&nbsp;Chee Khoon Lee","doi":"10.1016/j.lungcan.2025.108891","DOIUrl":"10.1016/j.lungcan.2025.108891","url":null,"abstract":"<div><h3>Background</h3><div>In NSCLC, <em>TP53</em> mutations are heterogeneous with varied effects on protein synthesis, function and clinical outcomes. We hypothesize that a refined classification of <em>TP53</em> mutations, beyond binary categorization, could improve prognostication. Furthermore, specific mutations could be associated with enhanced benefit from immune checkpoint inhibitors (ICI) versus chemotherapy. To investigate this, we analyzed data from randomized trials (OAK and POPLAR) which compared atezolizumab to chemotherapy in previously treated advanced driver-negative NSCLC.</div></div><div><h3>Methods</h3><div>Participants were classified as <em>TP53</em> mutant or wild-type using baseline plasma, and by coding mutation, and Olivier’s and Poeta’s classification. We performed multivariable Cox regression analyses to evaluate the prognostic significance of <em>TP53</em> mutations, and interaction tests to assess their predictive value.</div></div><div><h3>Results</h3><div>Among 762 participants, 49% harbored a <em>TP53</em> mutation. <em>TP53</em> mutations based on binary categorization were associated with poorer but not statistically significant OS compared to wild-type (adjusted-HR 1.15; 95 %CI 0.96–1.38; <em>P</em> = .12). However, nonsense mutations classified by coding mutations (adjusted-HR 1.71; 95% CI 1.22–2.39;<!--> <em>P</em> = .002), non-missense mutations classified by Olivier’s classification (adjusted-HR 1.33; 95% CI 1.03–1.74; <em>P</em> = .03) and disruptive mutations classified by Poeta’s classification (adjusted-HR 1.33; 95% CI 1.37–1.77; <em>P</em> = .03) were associated with statistically significant poorer OS. <em>TP53</em> status did not predict differential benefit from ICI versus chemotherapy (interaction <em>P</em> = .45).</div></div><div><h3>Conclusion</h3><div>In advanced driver-negative NSCLC following progression on first-line chemotherapy, nonsense, non-missense and disruptive mutations of <em>TP53</em> were strongly associated with inferior OS. These data support utilizing a nuanced classification of <em>TP53</em> mutations as a stratification factor in future trials, and laboratory reporting to aid prognostication.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108891"},"PeriodicalIF":4.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918105","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 role of APOBEC in early-stage epidermal growth factor receptor-mutant non-small cell lung cancer","authors":"Hyun Ae Jung ,&nbsp;Jinyeong Lim ,&nbsp;Yoon-La Choi ,&nbsp;Yeong Jeong Jeon ,&nbsp;Junghee Lee ,&nbsp;Jong Ho Cho ,&nbsp;Yong Soo Choi ,&nbsp;Sehhoon Park ,&nbsp;Jong-Mu Sun ,&nbsp;Jin Seok Ahn ,&nbsp;Myung-Ju Ahn ,&nbsp;Woong-Yang Park ,&nbsp;Hong Kwan Kim ,&nbsp;Se-Hoon Lee","doi":"10.1016/j.lungcan.2025.108892","DOIUrl":"10.1016/j.lungcan.2025.108892","url":null,"abstract":"<div><h3>Background</h3><div>APOBEC plays a crucial role in the mutation process and immune response of non-small cell lung cancer (NSCLC). This study evaluated the role of the APOBEC mutation signature in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC. This study aimed to assess the impact of APOBEC enrichment on recurrence-free survival (RFS), post-recurrence tyrosine kinase inhibitor (TKI) progression-free survival (PFS), and post-recurrence survival (PRS).</div></div><div><h3>Methods</h3><div>We conducted whole-exome sequencing and whole-transcriptome sequencing in 100 patients diagnosed with pathologic stage II-IIIA non-squamous NSCLC.</div></div><div><h3>Results</h3><div>Among the 100 patients, 18 (18 %) exhibited APOBEC (≥2) enrichment, which did not show a significant association with RFS (<em>P</em> = 0.14). Patients with APOBEC enrichment showed a shorter post-recurrence TKI PFS compared to those without APOBEC enrichment (8.13 months vs. 24.57 months, <em>P</em> = 0.017). In multivariate analysis, poor post-recurrence TKI PFS was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR = 1.91, <em>P</em> = 0.04), TP53 mutation (HR = 2.07, <em>P</em> = 0.03), and APOBEC enrichment (≥2 vs. &lt; 2, HR = 2.23, <em>P</em> = 0.02). PRS was 61.10 months and 21.77 months for patients with APOBEC enrichment and patients without APOBEC enrichment, respectively (<em>P</em> = 0.029). In multivariate analysis, poor PRS of EGFR-TKI was associated with the type of EGFR mutation (L858R vs. exon 19 deletion, HR = 2.29, <em>P</em> = 0.04) and APOBEC enrichment (≥2 vs. &lt; 2, HR = 2.71, <em>P</em> = 0.02).</div></div><div><h3>Conclusions</h3><div>APOBEC enrichment may present at initial diagnosis of early-stage <em>EGFR</em> mutant NSCLC and is associated with poor post-recurrence TKI PFS and PRS rather than RFS.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108892"},"PeriodicalIF":4.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878648","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":"Inavolisib for PIK3CA-mutant non-small cell lung cancer: A case report","authors":"Lei Cheng ,&nbsp;Dongying Wang ,&nbsp;Xueyan Zhang ,&nbsp;Baohui Han ,&nbsp;Hua Zhong ,&nbsp;Wei Nie","doi":"10.1016/j.lungcan.2025.108890","DOIUrl":"10.1016/j.lungcan.2025.108890","url":null,"abstract":"<div><h3>Introduction</h3><div><em>PIK3CA</em> mutations are oncogenic drivers in 2–4% of non-small cell lung cancers (NSCLC), often co-occurring with other drivers and conferring therapeutic resistance. This report is unique in describing the efficacy of the novel, highly selective PI3Kα inhibitor inavolisib in two heavily pre-treated patients with <em>PIK3CA</em>-mutant NSCLC harboring divergent co-drivers (<em>EGFR</em> and <em>KRAS</em>).</div></div><div><h3>Case presentation</h3><div>We present a 71-year-old male with <em>EGFR/PIK3CA</em>-mutant adenocarcinoma and brain metastases, and a 54-year-old female with <em>KRAS/PIK3CA</em>-mutant squamous cell carcinoma. Both patients reported rapid symptomatic improvement (hoarseness and shoulder pain, respectively) within two weeks of initiating inavolisib.</div></div><div><h3>Diagnosis, intervention, and outcomes</h3><div>Both patients received oral inavolisib (6 mg daily). Follow-up imaging after one month revealed significant tumor reduction. Notably, regressing intrapulmonary lesions exhibited tumor cavitation, and the male patient demonstrated a marked regression of central nervous system (CNS) metastases. The treatment was well-tolerated, with only Grade 1 oral mucositis reported.</div></div><div><h3>Conclusion</h3><div>The primary take-away lesson is that selective PI3Kα inhibition with inavolisib can induce potent systemic and intracranial responses in <em>PIK3CA</em>-mutant NSCLC, regardless of the primary oncogenic co-driver. The observed tumor cavitation suggests a potential anti-angiogenic mechanism, warranting further investigation.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"212 ","pages":"Article 108890"},"PeriodicalIF":4.4,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845517","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}