Shirish M Gadgeel, Misako Nagasaka, Karen Dziubek, Thomas Braun, Khaled Hassan, Haiying Cheng, Balazs Halmos, Antoinette Wozniak, James Stevenson, Pradnya Patil, Nathan Pennell, Mary Jo Fidler, Angel Qin, Zeqi Niu, Sunitha Nagrath, Gregory P Kalemkerian
{"title":"Pembrolizumab in Combination With Platinum-Based Chemotherapy in Patients With Recurrent EGFR and ALK Gene Altered Non-Small-Cell Lung Cancer (NSCLC).","authors":"Shirish M Gadgeel, Misako Nagasaka, Karen Dziubek, Thomas Braun, Khaled Hassan, Haiying Cheng, Balazs Halmos, Antoinette Wozniak, James Stevenson, Pradnya Patil, Nathan Pennell, Mary Jo Fidler, Angel Qin, Zeqi Niu, Sunitha Nagrath, Gregory P Kalemkerian","doi":"10.1016/j.cllc.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.09.002","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors have limited efficacy in patients with EGFR-mutant (EGFR+) and ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC). We conducted a phase II study to evaluate the efficacy of pembrolizumab with carboplatin and pemetrexed in these patients.</p><p><strong>Patients and methods: </strong>EGFR+ or ALK+ NSCLC patients, previously treated with targeted therapy, were eligible. Carboplatin, pemetrexed and pembrolizumab were administered every 3 weeks for 4 cycles followed by maintenance pemetrexed and pembrolizumab. The primary endpoint was response rate (RR). Blood for circulating tumor cells (CTCs) was collected prior to the 1st and 3rd cycles. The plan was to enroll 28 evaluable patients in both EGFR+ and ALK+ cohorts.</p><p><strong>Results: </strong>Of the 33 patients enrolled, 26 had EGFR+ and 7 had ALK+ NSCLC. RR (95% CI,) was 46% (27%, 67%) in EGFR+ and 29% (4%, 71%), in ALK+ patients, respectively. Median progression free survival (PFS) and overall survival (OS) in the EGFR+ cohort were 8.3 months (7.2-16.5) and 22.2 months (20.6-NE), respectively. In the ALK+ cohort, median PFS and OS were both 2.9 months. The median CTC count at baseline in 15 evaluable EGFR+ patients was 4 cells/mL (0-23). OS among EGFR+ patients with decreasing vs. increasing CTC count during treatment was not reached vs. 18.5 months, respectively (P = .52). The most common adverse events were fatigue, nausea, anemia and AST/ALT elevation.</p><p><strong>Conclusion: </strong>Pembrolizumab in combination with chemotherapy demonstrated encouraging RR of 42% and OS of 22 months among patients with recurrent EGFR+ NSCLC. The efficacy in ALK+ patients was not encouraging.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228514","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}
Brook M Lobsiger, Ashley S Huh-Brown, Jacob S Edmisson, Brock O'Keefe, Jinesh Gheeya, Mark B Botros, Asrar A AlAhmadi, Misty D Shields
{"title":"Tarlatamab-Induced Tumor Lysis Syndrome in Small Cell Carcinoma: Case Series.","authors":"Brook M Lobsiger, Ashley S Huh-Brown, Jacob S Edmisson, Brock O'Keefe, Jinesh Gheeya, Mark B Botros, Asrar A AlAhmadi, Misty D Shields","doi":"10.1016/j.cllc.2025.09.008","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.09.008","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318151","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":"A Phase II Study of Accelerated Hyperfractionated Thoracic Radiotherapy With Dose Escalation to 54 Gy With Concurrent Cisplatin and Etoposide for Limited-Stage Small-Cell Lung Cancer: Long-Term Results at a Single Institution.","authors":"Kanji Matsuura, Ritsuko Komaki, Miho Kono, Tsuyoshi Kudo, Ayaka Ono, Tsubasa Kameoka, Ikumi Shintani, Hayate Kusaba, Atsushi Kawakubo, Yasuharu Ando, Kiyoto Nishihara, Yasuo Iwamoto, Hiroyasu Shoda, Tsuyoshi Katsuta, Masayuki Kagemoto","doi":"10.1016/j.cllc.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.09.003","url":null,"abstract":"<p><strong>Purpose: </strong>The combination of 45 Gy accelerated hyperfractionated thoracic radiotherapy (AHF-TRT) and concurrent chemotherapy is the standard treatment for limited-stage small-cell lung cancer (LS-SCLC). However, the optimal dose and fractionation remain controversial. We herein report the long-term results of a phase II study investigating the utility of dose escalation to 54 Gy in AHF-TRT for LS-SCLC.</p><p><strong>Methods and materials: </strong>We enrolled patients with pathologically confirmed LS-SCLC. The radiation dose was 54 Gy, delivered in 36 fractions over 3.6 weeks. All patients were treated with 3D-CRT with multiple fields to reduce the elevated dose volume to the surrounding tissues. The chemotherapy regimens consisted of either cisplatin and etoposide or carboplatin and etoposide. All patients were evaluated for overall survival (OS), progression-free survival (PFS), and nonhematological toxicity.</p><p><strong>Results: </strong>Between 2013 and 2019, 21 patients were enrolled in this study. All the patients were assessed for their response and toxicities. The median age was 70 years and 15 patients were male, while 6 were female. The median follow-up period of all patients was 57.3 months. The 2- and 5-year OS rates were 85.7% and 47.6% respectively. The 2- and 5-year PFS rates were 52.3% and 47.6% respectively. No patient experienced grade ≥ 3 nonhematological adverse effects either during treatment or in follow-up.</p><p><strong>Conclusions: </strong>In this phase II study, AHF-TRT of 54 Gy resulted in a good OS and PFS without increasing severe toxicities. These outcomes suggest that dose escalation to 54 Gy may be a promising radical treatment for LS-SCLC.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273922","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":"Efficacy of Adjuvant Chemotherapy in Stage IA Lung Adenocarcinoma with Tumor Spread Through Air Spaces: A Multi-Center Real-World Study.","authors":"Hanbo Pan, Weiyang Huang, Wanlin Yang, Ling Li, Zhen Ge, Weicheng Kong, Hang Chen, Yu Tian, Wanyu Li, Junwei Ning, Liang Fang, Zhongjie Chen, Guomo Ruan, Zhizhuo Dai, Min Zheng, Ming Zhang, Hui Wang, Xiaomin Niu, Jia Huang, Hui Yin, Chengwei Zhou, Guodong Xu, Qingquan Luo","doi":"10.1016/j.cllc.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.09.004","url":null,"abstract":"<p><strong>Background: </strong>The role of adjuvant chemotherapy (ACT) for stage IA lung adenocarcinoma (LUAD) with tumor spread through air spaces (STAS) remains inconclusive. This study aimed to evaluate the efficacy of ACT in stage IA STAS<sup>+</sup> LUAD patients and to identify subpopulations that might derive clinically significant benefits from ACT.</p><p><strong>Methods: </strong>Consecutive pathological stage IA (T1a-cN0M0) STAS<sup>+</sup> LUAD patients who underwent surgery, with or without ACT, between 2012 and 2020 across 6 high-volume centers were retrospectively reviewed. Propensity-score matching (PSM) was performed to minimize selection bias. The primary endpoint was overall survival. Clinically significant survival benefits were predefined as a hazard ratio (HR) < 0.70, or HR < 0.75 with an absolute 5-year survival improvement > 5%.</p><p><strong>Results: </strong>Among 3026 eligible cases, 2619 patients (873 ACT and 1746 no ACT) were matched by PSM, achieving well-balanced clinicopathological characteristics. Over a median follow-up of 6.88 years, ACT did not confer clinically significant improvements in overall survival (hazard ratio = 0.795, P = .010) in the overall cohort. Cox regression analyses identified age, histology subtype, lymphovascular invasion (LVI), resection extent, and pathological stage as independent prognostic factors. Interaction analyses further revealed that histology subtype, LVI, and resection extent, but not age or pathological stage, modified ACT's effect on survival. Exploratory stratified analyses demonstrated that ACT may be associated with clinically significant survival benefits among patients undergoing sub-lobectomy, those with LVI<sup>+</sup> tumors, and those with solid/micropapillary-predominant histology.</p><p><strong>Conclusions: </strong>Although ACT demonstrated limited clinical survival benefit for the overall stage IA STAS<sup>+</sup> LUAD population, it may be necessary for selected high-risk subgroups, specifically those undergoing sub-lobectomy, with LVI<sup>+</sup> tumors, or with solid/micropapillary-predominant histology.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291373","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":"Revisiting AI Model Interpretability in Lung Cancer Screening: Challenges in Balancing Predictive Performance and Reliability.","authors":"Souichi Oka, Yoshiyasu Takefuji","doi":"10.1016/j.cllc.2025.09.005","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.09.005","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279101","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}
M Judy Lubas, Albi Vata, Jordan Fredette, Martin J Edelman, Sameera Kumar
{"title":"An Institution-Specific Hypofractionated Radiation Therapy Regimen in the Treatment of Central and Ultracentral Non-small Cell Lung Cancer.","authors":"M Judy Lubas, Albi Vata, Jordan Fredette, Martin J Edelman, Sameera Kumar","doi":"10.1016/j.cllc.2025.08.018","DOIUrl":"10.1016/j.cllc.2025.08.018","url":null,"abstract":"<p><strong>Purpose/objectives: </strong>While stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy (HFRT) is routinely used to treat inoperable early-stage non-small lung cancer (esNSCLC) patients with peripheral tumors, SBRT or HFRT for central (cenT) and ultracentral tumors (UCT) remains controversial. To treat patients with tumors located within 0-2 cm of critical mediastinal structures (CMSTs), we employ an institution specific hypofractionated radiation regimen (isHFRT) with a biologically effective dose (BED) of 98.59 using 17 fractions to a dose of 6987 cGy.</p><p><strong>Methods: </strong>We conducted a single-institution retrospective review of patients with esNSCLC treated with this isHFRT between 2011 and 2020, evaluating both tumor control rates and rates of treatment related toxicity.</p><p><strong>Results: </strong>Of the 31 patients evaluated, 61.3% of patients had UCTs while 38.7% had cenTs. At 1- and 3 years, local control (LC) was noted to be 93.5% and 86.8% respectively. 1-year overall survival (OS) was 74.2% for all comers, 75.0% for patients with cenTs and 73.7% for patients with UCTs (p = 0.70). 3-year OS was 20.8%. Only 22.6% of patients who expired at 1-year experienced disease progression. At 12 months, adverse event free survival (AEFS) was 67.7%. While 25.8% (n = 8) of patients experienced a Grade 2 (G2) or greater toxicity, no patient experienced a G2 or greater cardiotoxicity. Only 1 patient (3.3%) experienced a Grade 5 toxicity (fatal hemoptysis 12-months following treatment). Review of the case demonstrated that the maximum tracheobronchial tree dose had been exceeded.</p><p><strong>Conclusions: </strong>Our isHFRT for patients with esNSCLC proves a safe and effective treatment for medically inoperable esNSCLC patients with cenTs and UCTs with comparable rates of toxicity when compared to prior studies.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181852","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}
James Ch Yang, Myung-Ju Ahn, Joo-Hang Kim, Yun-Gyoo Lee, Ji-Youn Han, Ki Hyeong Lee, Anastasia Zimina, Dong-Wan Kim, Kyung-Hee Lee, Sung Sook Lee, Chun Sen Lim, Yueh Ni Lim, Young Joo Min, Sergey Orlov, Youngjoo Lee, YuKyung Kim, Mi-Jung Kwon, Hana Lee, Hyeonchae Cho, Byoung Chul Cho
{"title":"Central Nervous System Outcomes of Lazertinib Treatment in EGFR-Mutated Advanced NSCLC: Pooled Analysis From LASER201 and LASER301.","authors":"James Ch Yang, Myung-Ju Ahn, Joo-Hang Kim, Yun-Gyoo Lee, Ji-Youn Han, Ki Hyeong Lee, Anastasia Zimina, Dong-Wan Kim, Kyung-Hee Lee, Sung Sook Lee, Chun Sen Lim, Yueh Ni Lim, Young Joo Min, Sergey Orlov, Youngjoo Lee, YuKyung Kim, Mi-Jung Kwon, Hana Lee, Hyeonchae Cho, Byoung Chul Cho","doi":"10.1016/j.cllc.2025.08.007","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.08.007","url":null,"abstract":"<p><strong>Background: </strong>Lazertinib, a brain-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), significantly improved efficacy in patients with treatment-naïve, EGFR-mutated advanced non-small cell lung cancer (NSCLC) in the clinical trials, LASER201 and LASER301. This analysis evaluated the efficacy and safety of lazertinib in patients with EGFR-mutated NSCLC and CNS metastases using pooled data from LASER201 and LASER301.</p><p><strong>Patients and methods: </strong>Patients with treatment-naïve, EGFR-mutated advanced NSCLC and stable CNS metastases who were treated with lazertinib in a cohort of LASER201 and LASER301 were included. Intracranial progression-free survival (iPFS), intracranial objective response rate (iORR), intracranial disease control rate (iDCR), intracranial duration of response (iDoR), and treatment-emergent adverse events (TEAEs) were assessed.</p><p><strong>Results: </strong>A total of 64 patients were included in the intracranial full analysis set (iFAS); 24 patients had at least 1 measurable CNS lesion at baseline. The median iPFS was 27.7 months (95% CI: 15.7-32.8) in the iFAS population. For patients with at least 1 measurable CNS lesion at baseline, iORR was 92% and iDCR was 96%. The median iDoR was 26.5 months (95% CI: 8.3-30.1). TEAEs were reported in 98% of patients in the iFAS population, with grade ≥3 TEAEs occurring in 55% of patients. The most common TEAEs were paresthesia (47%), rash (41%), and pruritus (36%).</p><p><strong>Conclusion: </strong>In this pooled analysis of LASER201 and LASER301, lazertinib demonstrated a clinically meaningful treatment benefit and consistent safety profile in patients with EGFR-mutated advanced NSCLC and CNS metastases.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257528","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}
Marta Brambilla, Francesca Barbetta, Giuseppe Nardo, Luca Agnelli, Giorgia Di Liberti, Paolo Ambrosini, Chiara Cavalli, Adele Busico, Iolanda Capone, Daniele Lorenzini, Filippo de Braud, Giancarlo Pruneri
{"title":"Refining High-Risk EGFR-Mutant Lung Cancer Patients: The Role of Adjusted Variant Allele Frequency in First-Line Osimertinib Therapy.","authors":"Marta Brambilla, Francesca Barbetta, Giuseppe Nardo, Luca Agnelli, Giorgia Di Liberti, Paolo Ambrosini, Chiara Cavalli, Adele Busico, Iolanda Capone, Daniele Lorenzini, Filippo de Braud, Giancarlo Pruneri","doi":"10.1016/j.cllc.2025.08.014","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.08.014","url":null,"abstract":"<p><p>Next-Generation Sequencing (NGS) has an increasing role in patients with advanced non-small-cell lung cancer (aNSCLC) and, in parallel, the use of targeted therapy dramatically improves the outcome of those with actionable alterations. In this scenario, the possible prognostic significance of some features provided by NGS testing and, among these, of Variant Allele Frequency (VAF), is still unclear. Herein, we report a real-world single-center prospective cohort of 88 consecutive patients with aNSCLC profiled by NGS and harboring a classic EGFR mutation, who were treated with the standard first-line tyrosine kinase inhibitor osimertinib. A subset of patients with shorter progression-free survival (PFS) was characterized by extremely high VAF/tumor cellularity, >1.7 adjusted VAF (aVAF). Median PFS was 5.3 months shorter in the high aVAF cohort; a similar trend was observed in overall survival too. No significant association between aVAF and TP53 mutations, Tumor Mutational Burden or other clinical, pathological or molecular features was found. Our findings suggest that NGS could improve the traditional binary classification of EGFR mutations in aNSCLC, highlighting a correlation between high EGFR mutations aVAF and worse outcome.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112139","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}
Sneha S Alaparthi, Anurag Ishwar, Gregory Whitehorn, Isheeta Madeka, Tyler Grenda, John D Jacob, Nathaniel R Evans Iii, Olugbenga T Okusanya
{"title":"Is Lobectomy Associated With Improved Outcomes Compared to Segmentectomy in Small Cell Lung Cancer Discovered at the Time of Resection?","authors":"Sneha S Alaparthi, Anurag Ishwar, Gregory Whitehorn, Isheeta Madeka, Tyler Grenda, John D Jacob, Nathaniel R Evans Iii, Olugbenga T Okusanya","doi":"10.1016/j.cllc.2025.08.017","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.08.017","url":null,"abstract":"<p><strong>Background: </strong>Small cell lung cancer (SCLC) represents approximately 10%-15% of all lung cancer cases in the United States. The extent of surgery for early-stage SCLC remains controversial,with the treatment standard being chemotherapy or chemoradiotherapy. We aim to evaluate outcomes among the patients who underwent a lobectomy or segmentectomy in SCLC diagnosed on the day of resection.</p><p><strong>Methods: </strong>This retrospective cohort study utilized the NCDB. We examined patients >18 who underwent a lobectomy or segmentectomy between 2010 and 2019 who had clinically node negative SCLC diagnosed at the time of resection. Outcome variables include 5- year, 30-day, 90-day mortality and readmission rates. Propensity score matching was utilized to compare outcomes between groups.</p><p><strong>Results: </strong>564 patients were examined, with a mean age of 68. Males comprised of 42.9% of the cohort. 65 (12%) patients underwent segmentectomy and 499 (88%) patients underwent lobectomy. There were no differences in nodal upstaging (P = .31) and T stage upstaging (P = .37) between the 2 cohorts. 90.2% of the population was clinical stage I (P = .003). There were no significant differences in 5- year, 30-day, 90-day mortality (P = .22, P = .40, P = .77), and readmission (P = .57) in this cohort. After PSM (n = 118) there continued to be no significant difference in all outcomes between cohorts.</p><p><strong>Conclusions: </strong>In this study, we found that rates of T and N upstaging, 5-year mortality, and short-term outcomes did not differ amongst cohorts, showing that patients who undergo segmentectomy may not benefit from undergoing a more extensive resection.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205839","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 Epidermal Growth Factor Receptor-Mutant Nonsmall-Cell Lung Cancer Patients Benefiting From Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.","authors":"Haodi Zhou, Beiyu Liang, Li-Chin Lu, Chia-Pang Chan, Jun-He Yang, Shao-Huan Lan","doi":"10.1016/j.cllc.2025.08.008","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.08.008","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are used in epidermal growth factor receptor (EGFR)-mutant nonsmall-cell lung cancer (NSCLC) after resistance to targeted therapy; however, responses remain limited. This study identified predictors of ICI efficacy to inform treatment strategies.</p><p><strong>Methods: </strong>PubMed, EMBASE, and Web of Science were systematically searched through September 17, 2024, for studies examining associations between clinical benefit and patient characteristics during ICI therapy. Progression-free survival and overall survival were used to determine outcomes.</p><p><strong>Results: </strong>We included 18 studies involving 1151 patients. Combination therapy improved outcomes: ICI plus antiangiogenic therapy versus ICI monotherapy (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.36-1.52) and ICI plus chemotherapy versus ICI monotherapy (HR = 0.45, 95% CI: 0.32-0.65). Predictive genetic factors included atypical versus classical EGFR mutations (HR = 0.45, 95% CI: 0.32-0.64) and exon 21 L858R versus exon 19 deletions (HR = 0.53, 95% CI: 0.40-0.71). Favorable biomarkers included low neutrophil-to-lymphocyte ratio (NLR; HR = 1.90, 95% CI: 1.16-3.11) and positive programmed death ligand-1 (PD-L1) expression (HR = 0.58, 95% CI: 0.35-0.96). Poor Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) was associated with poor outcomes (HR = 2.03, 95% CI: 1.37-3.01). Age, sex, smoking status, and histological subtype exhibited weaker or nonsignificant associations.</p><p><strong>Conclusion: </strong>Patients with atypical EGFR or L858R mutations, high PD-L1 expression, low NLR, and good ECOG-PS are more likely to benefit from ICI therapy. Combining ICIs with chemotherapy or antiangiogenic agents enhances efficacy. Younger age, smoking history, and squamous cell carcinoma may also associate with improved outcomes, but further validation is required.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148118","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}