Pub Date : 2026-01-30DOI: 10.1016/j.cllc.2026.01.007
Diana Kim, Sarah Blocker, Courtney C Cavalieri, Sabrina Cannon, Amanda S Cass, Alexander Olinger, Bryce Bortka, Beth Gustafson, Allison Schepers, Jacob Hobbs, Lauren Blackwell, Kori Holman, Wilder Widman, Austin Quick, Dennis Grauer, Manidhar Reddy Lekkala, Chao Huang, Prakash Neupane, Jun Zhang, Sanjana Mullangi, Timothy Schieber
Background: Small cell lung cancer (SCLC) is an aggressive malignancy in which radiotherapy remains integral across both limited and extensive stages (ES-SCLC). Tarlatamab has shown improved survival versus chemotherapy and is the preferred second-line therapy. Early tarlatamab studies restricted radiotherapy use limiting knowledge of concurrent use. We evaluated the safety and efficacy of real-world concurrent radiotherapy with tarlatamab in ES-SCLC using the DLL3 PanTUMOR database.
Methods: We performed a multicenter retrospective analysis of adults treated with tarlatamab for ES-SCLC between May 2024 and July 2025. Patients receiving radiotherapy after tarlatamab initiation were assigned to the concurrent radiation arm; others formed the nonradiotherapy (non-RT) arm. The primary endpoint was the rate of grade ≥ 3 adverse events attributed to radiotherapy. Secondary endpoints included overall survival (OS), progression-free survival (PFS), tumor regression at irradiated sites, discontinuation due to adverse events, and maximum CRS or ICANS grade.
Results: Among 109 patients (23 concurrent RT, 86 non-RT), baseline characteristics were balanced. Stereotactic radiotherapy was most common (56.5%), predominantly to the brain. Only 1 patient (4.3%) experienced grade ≥ 3 radiotherapy-related toxicity after whole-brain radiotherapy. Median OS was not reached in the concurrent RT arm versus 7.5 months in non-RT (P = .155); median PFS was 4.6 versus 3.1 months (P = .606). Tumor regression occurred in 5 of 6 evaluable patients (83.3%). No delayed CRS or ICANS were observed after the tarlatamab step-up phase.
Conclusions: Concurrent radiotherapy with tarlatamab is safe, with low severe toxicity, frequent local tumor response, and a trend toward improved OS, supporting further study in ES-SCLC.
{"title":"Outcomes of Concurrent Radiotherapy With Tarlatamab in Extensive-Stage Small Cell Lung Cancer From the DLL3 PanTUMOR Database.","authors":"Diana Kim, Sarah Blocker, Courtney C Cavalieri, Sabrina Cannon, Amanda S Cass, Alexander Olinger, Bryce Bortka, Beth Gustafson, Allison Schepers, Jacob Hobbs, Lauren Blackwell, Kori Holman, Wilder Widman, Austin Quick, Dennis Grauer, Manidhar Reddy Lekkala, Chao Huang, Prakash Neupane, Jun Zhang, Sanjana Mullangi, Timothy Schieber","doi":"10.1016/j.cllc.2026.01.007","DOIUrl":"https://doi.org/10.1016/j.cllc.2026.01.007","url":null,"abstract":"<p><strong>Background: </strong>Small cell lung cancer (SCLC) is an aggressive malignancy in which radiotherapy remains integral across both limited and extensive stages (ES-SCLC). Tarlatamab has shown improved survival versus chemotherapy and is the preferred second-line therapy. Early tarlatamab studies restricted radiotherapy use limiting knowledge of concurrent use. We evaluated the safety and efficacy of real-world concurrent radiotherapy with tarlatamab in ES-SCLC using the DLL3 PanTUMOR database.</p><p><strong>Methods: </strong>We performed a multicenter retrospective analysis of adults treated with tarlatamab for ES-SCLC between May 2024 and July 2025. Patients receiving radiotherapy after tarlatamab initiation were assigned to the concurrent radiation arm; others formed the nonradiotherapy (non-RT) arm. The primary endpoint was the rate of grade ≥ 3 adverse events attributed to radiotherapy. Secondary endpoints included overall survival (OS), progression-free survival (PFS), tumor regression at irradiated sites, discontinuation due to adverse events, and maximum CRS or ICANS grade.</p><p><strong>Results: </strong>Among 109 patients (23 concurrent RT, 86 non-RT), baseline characteristics were balanced. Stereotactic radiotherapy was most common (56.5%), predominantly to the brain. Only 1 patient (4.3%) experienced grade ≥ 3 radiotherapy-related toxicity after whole-brain radiotherapy. Median OS was not reached in the concurrent RT arm versus 7.5 months in non-RT (P = .155); median PFS was 4.6 versus 3.1 months (P = .606). Tumor regression occurred in 5 of 6 evaluable patients (83.3%). No delayed CRS or ICANS were observed after the tarlatamab step-up phase.</p><p><strong>Conclusions: </strong>Concurrent radiotherapy with tarlatamab is safe, with low severe toxicity, frequent local tumor response, and a trend toward improved OS, supporting further study in ES-SCLC.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303035","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}
Pub Date : 2026-01-20DOI: 10.1016/j.cllc.2026.01.004
Xiaoqian Zhai, Zuoyu Liang, Cheng Zhen, Ni Zhai, Guowei Che, Qinghua Zhou, Weiya Wang
{"title":"First Frameshift Mutation of ALK in Non-Small Cell Lung Cancer Remaining Sensitive to Alectinib: Case Report.","authors":"Xiaoqian Zhai, Zuoyu Liang, Cheng Zhen, Ni Zhai, Guowei Che, Qinghua Zhou, Weiya Wang","doi":"10.1016/j.cllc.2026.01.004","DOIUrl":"https://doi.org/10.1016/j.cllc.2026.01.004","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282564","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}
Pub Date : 2026-01-19DOI: 10.1016/j.cllc.2026.01.005
Giannis Mountzios, Julius K Weng, Eleni Zairi, Kristin Hsieh, Pratibha Chander, William Dunlop, Yao Qiao, Alice Wang, Adam Januszewski
Introduction: Many patients with unresectable stage III non-small-lung cancer (NSCLC) may face challenges in receiving consolidation durvalumab following concurrent chemoradiotherapy (cCRT) due to incomplete cCRT or disease progression. The retrospective POSITION study characterized this population.
Methods: Adults with unresectable stage III NSCLC diagnosed between 2010 and 2021 who received cCRT were identified from TEMPUS Oncology (database). Among these patients, we estimated proportions with incomplete cCRT or progression during/within 42 days of cCRT and assessed overall survival (OS). Factors associated with incomplete cCRT or progression during/within 42 days of cCRT were identified via multivariable logistic regression.
Results: Of 2076 eligible patients, 23.0% had incomplete cCRT (Group A), 12.7% experienced progression during/within 42 days of cCRT (Group B), and 64.3% completed cCRT without progression (Group C). Median OS (95% CI) was 21.6 (17.2-28.0), 10.1 (7.2-12.5), and 32.4 (29.8-34.6) months for Groups A, B, and C, respectively. Landmark 60-month OS rates were 26.3%, 11.6% and 33.2% for Groups A, B and C, respectively. Higher comorbidity burden (Charlson Comorbidity Index) and Black (vs. White) race were associated with higher likelihood of incomplete cCRT. Stage IIIB/C (vs. IIIA), cerebrovascular, and renal disease were associated with higher likelihood of progression during/within 42 days of cCRT.
Conclusion: In POSITION, 35.7% of patients had incomplete cCRT or progressed during/within 42 days of cCRT and may have faced challenges receiving consolidation durvalumab; race, disease stage, and comorbidities were associated with incomplete cCRT or progression.
{"title":"Characterizing Risk Factors and Outcomes in Patients With Unresectable, Stage III Non-Small-Cell Lung Cancer Who Do Not Complete, or Who Experience Progression During/Within 42 Days of, Concurrent Chemoradiotherapy: The POSITION Study.","authors":"Giannis Mountzios, Julius K Weng, Eleni Zairi, Kristin Hsieh, Pratibha Chander, William Dunlop, Yao Qiao, Alice Wang, Adam Januszewski","doi":"10.1016/j.cllc.2026.01.005","DOIUrl":"https://doi.org/10.1016/j.cllc.2026.01.005","url":null,"abstract":"<p><strong>Introduction: </strong>Many patients with unresectable stage III non-small-lung cancer (NSCLC) may face challenges in receiving consolidation durvalumab following concurrent chemoradiotherapy (cCRT) due to incomplete cCRT or disease progression. The retrospective POSITION study characterized this population.</p><p><strong>Methods: </strong>Adults with unresectable stage III NSCLC diagnosed between 2010 and 2021 who received cCRT were identified from TEMPUS Oncology (database). Among these patients, we estimated proportions with incomplete cCRT or progression during/within 42 days of cCRT and assessed overall survival (OS). Factors associated with incomplete cCRT or progression during/within 42 days of cCRT were identified via multivariable logistic regression.</p><p><strong>Results: </strong>Of 2076 eligible patients, 23.0% had incomplete cCRT (Group A), 12.7% experienced progression during/within 42 days of cCRT (Group B), and 64.3% completed cCRT without progression (Group C). Median OS (95% CI) was 21.6 (17.2-28.0), 10.1 (7.2-12.5), and 32.4 (29.8-34.6) months for Groups A, B, and C, respectively. Landmark 60-month OS rates were 26.3%, 11.6% and 33.2% for Groups A, B and C, respectively. Higher comorbidity burden (Charlson Comorbidity Index) and Black (vs. White) race were associated with higher likelihood of incomplete cCRT. Stage IIIB/C (vs. IIIA), cerebrovascular, and renal disease were associated with higher likelihood of progression during/within 42 days of cCRT.</p><p><strong>Conclusion: </strong>In POSITION, 35.7% of patients had incomplete cCRT or progressed during/within 42 days of cCRT and may have faced challenges receiving consolidation durvalumab; race, disease stage, and comorbidities were associated with incomplete cCRT or progression.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316572","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}
Pub Date : 2026-01-07DOI: 10.1016/j.cllc.2025.12.007
Fabio Gomes, Niall Gilding, Vivian Tan, Katerina Christoforou, Joanne Rule, Amine Aziez, Adam Januszewski, Anna Minchom
Objectives: Real-world analyses of first-line maintenance (1LM) immuno-oncology (IO) treatment with or without pemetrexed for patients with non-squamous (NSQ) advanced/metastatic non-small cell cancer (a/mNSCLC), including the relative impact of 1LM pemetrexed, are lacking. This retrospective analysis describes 1LM treatment patterns and their outcomes in England.
Methods: Data from the National Disease Registration Service were collated to identify 2 cohorts of patients with NSQ a/mNSCLC completing ≥ 4 cycles of first-line (1L) platinum-based chemotherapy with IO plus pemetrexed, diagnosed from 1 March to 31 December 2019 (Cohort 1), or during a period where interim coronavirus disease 2019 (COVID-19) guidelines were in effect (1 March to 31 December 2020; Cohort 2). Baseline characteristics, 1LM treatment, overall survival (OS) and time to next treatment or death in both cohorts, and in a combined cohort of patients receiving 1LM stratified by the presence/absence of 1LM pemetrexed, were analyzed.
Results: Overall, 595 and 516 NSQ a/mNSCLC patients were included in Cohorts 1 and 2, respectively. Median OS (95% confidence interval [CI], months) from start of 1L was numerically longer in Cohort 1 (19.5 [17.6-22.2] months) versus Cohort 2 (15.7 [14.2-18.0] months). Combined (Cohort 1 and Cohort 2) median OS from 1L was broadly similar irrespective of pemetrexed presence (19.5 [17.5-21.6] months) or absence (18.6 [15.6-23.0] months) in 1LM.
Conclusions: Survival was numerically shorter for patients diagnosed during the COVID-19 pandemic (Cohort 2; interim guidance) versus Cohort 1 (pre-COVID-19). In a combined cohort, survival was broadly similar regardless of 1LM pemetrexed use.
{"title":"Impact of First-Line Maintenance Immunotherapy With or Without Pemetrexed for Non-Squamous Advanced/Metastatic Non-Small Cell Lung Cancer Lacking Targetable Mutations: A Real-World Analysis in England.","authors":"Fabio Gomes, Niall Gilding, Vivian Tan, Katerina Christoforou, Joanne Rule, Amine Aziez, Adam Januszewski, Anna Minchom","doi":"10.1016/j.cllc.2025.12.007","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.12.007","url":null,"abstract":"<p><strong>Objectives: </strong>Real-world analyses of first-line maintenance (1LM) immuno-oncology (IO) treatment with or without pemetrexed for patients with non-squamous (NSQ) advanced/metastatic non-small cell cancer (a/mNSCLC), including the relative impact of 1LM pemetrexed, are lacking. This retrospective analysis describes 1LM treatment patterns and their outcomes in England.</p><p><strong>Methods: </strong>Data from the National Disease Registration Service were collated to identify 2 cohorts of patients with NSQ a/mNSCLC completing ≥ 4 cycles of first-line (1L) platinum-based chemotherapy with IO plus pemetrexed, diagnosed from 1 March to 31 December 2019 (Cohort 1), or during a period where interim coronavirus disease 2019 (COVID-19) guidelines were in effect (1 March to 31 December 2020; Cohort 2). Baseline characteristics, 1LM treatment, overall survival (OS) and time to next treatment or death in both cohorts, and in a combined cohort of patients receiving 1LM stratified by the presence/absence of 1LM pemetrexed, were analyzed.</p><p><strong>Results: </strong>Overall, 595 and 516 NSQ a/mNSCLC patients were included in Cohorts 1 and 2, respectively. Median OS (95% confidence interval [CI], months) from start of 1L was numerically longer in Cohort 1 (19.5 [17.6-22.2] months) versus Cohort 2 (15.7 [14.2-18.0] months). Combined (Cohort 1 and Cohort 2) median OS from 1L was broadly similar irrespective of pemetrexed presence (19.5 [17.5-21.6] months) or absence (18.6 [15.6-23.0] months) in 1LM.</p><p><strong>Conclusions: </strong>Survival was numerically shorter for patients diagnosed during the COVID-19 pandemic (Cohort 2; interim guidance) versus Cohort 1 (pre-COVID-19). In a combined cohort, survival was broadly similar regardless of 1LM pemetrexed use.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194251","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}
Pub Date : 2026-01-01Epub Date: 2025-11-19DOI: 10.1016/j.cllc.2025.11.012
Xinyang Li , Shiwen Song
{"title":"Lazertinib in EGFR-Mutated NSCLC with CNS Metastases: Reinforcing the Role of Third-Generation TKIs through Pooled Analysis","authors":"Xinyang Li , Shiwen Song","doi":"10.1016/j.cllc.2025.11.012","DOIUrl":"10.1016/j.cllc.2025.11.012","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 1","pages":"Page 74"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732956","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}
Pub Date : 2026-01-01Epub Date: 2025-11-07DOI: 10.1016/j.cllc.2025.11.005
Julia G. Katcher , Christine C. Shusted , Padmanabh Bhatt , Brooke M. Ruane , Jenna Markle , Gregory C. Kane , Kuang-Yi Wen , Hee-Soon Juon , Julie A. Barta
•
Among screening-eligible adults, lung cancer is diagnosed more often in those with family history of lung cancer
•
Patients with family history had higher frequency of stage IV disease
•
Considering family history in risk assessment could improve lung cancer screening strategies
{"title":"Brief Report: Lung Cancer Diagnoses among Lung Cancer Screening Program Participants With Family History of Lung Cancer","authors":"Julia G. Katcher , Christine C. Shusted , Padmanabh Bhatt , Brooke M. Ruane , Jenna Markle , Gregory C. Kane , Kuang-Yi Wen , Hee-Soon Juon , Julie A. Barta","doi":"10.1016/j.cllc.2025.11.005","DOIUrl":"10.1016/j.cllc.2025.11.005","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Among screening-eligible adults, lung cancer is diagnosed more often in those with family history of lung cancer</div></span></li><li><span>•</span><span><div>Patients with family history had higher frequency of stage IV disease</div></span></li><li><span>•</span><span><div>Considering family history in risk assessment could improve lung cancer screening strategies</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 1","pages":"Pages 34-37"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619919","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}
Pub Date : 2026-01-01Epub Date: 2025-11-17DOI: 10.1016/j.cllc.2025.11.009
Alexander I. Spira , David Berz , Robert M. Jotte , Krishna K. Pachipala , Mark S. Berger
Background
Expression of TUSC2, a tumor suppressor gene, is decreased in 82% of patients with NSCLC. Quaratusugene ozeplasmid gene therapy consists of a plasmid containing the TUSC2 gene encapsulated in lipid nanoparticles that restores TUSC2 expression, and thus is a new approach to cancer treatment.
Patients and Methods
Patients had NSCLC with EGFR mutations and progression on osimertinib regimens. Quaratusugene ozeplasmid was administered IV every 21 days at 3 dose levels with osimertinib 80 mg PO daily. Dexamethasone, acetaminophen, and diphenhydramine were administered prophylactically. Dose limiting toxicities (DLTs) were generally defined as ≥ Grade (Gr) 3 adverse events (AEs).
Results
Twelve patients were enrolled (3M/9F), median age 59.5, with 3 at 0.06 mg/kg, 4 at 0.09 mg/kg, and 5 at 0.12 mg/kg. There were no DLTs. There was a delayed infusion-related reaction with muscle aches, headache, and pyrexia. One patient at the 0.06 mg/kg dose level had a partial response (PR) and no progression for more than 32 months. Two other patients had stable disease (SD) for 22 and 9 months before disease progression.
Conclusion
Among the 12 patients treated with escalating doses of quaratusugene ozeplasmid and standard doses of osimertinib there were 3 patients with prolonged time to progression, including 1 with continuing PR. Quaratusugene ozeplasmid administration was associated with a delayed infusion-related reaction managed with prophylactic steroids, acetaminophen and diphenhydramine. There were no DLTs. The recommended phase II dose of quaratusugene ozeplasmid in combination with osimertinib in patients with NSCLC progressing after osimertinib treatment is 0.12 mg/kg.
{"title":"Dose Escalation Trial of the Combination of Osimertinib and Quaratusugene Ozeplasmid Gene Therapy in Patients with Advanced NSCLC","authors":"Alexander I. Spira , David Berz , Robert M. Jotte , Krishna K. Pachipala , Mark S. Berger","doi":"10.1016/j.cllc.2025.11.009","DOIUrl":"10.1016/j.cllc.2025.11.009","url":null,"abstract":"<div><h3>Background</h3><div>Expression of TUSC2, a tumor suppressor gene, is decreased in 82% of patients with NSCLC. Quaratusugene ozeplasmid gene therapy consists of a plasmid containing the TUSC2 gene encapsulated in lipid nanoparticles that restores TUSC2 expression, and thus is a new approach to cancer treatment.</div></div><div><h3>Patients and Methods</h3><div>Patients had NSCLC with EGFR mutations and progression on osimertinib regimens. Quaratusugene ozeplasmid was administered IV every 21 days at 3 dose levels with osimertinib 80 mg PO daily. Dexamethasone, acetaminophen, and diphenhydramine were administered prophylactically. Dose limiting toxicities (DLTs) were generally defined as ≥ Grade (Gr) 3 adverse events (AEs).</div></div><div><h3>Results</h3><div>Twelve patients were enrolled (3M/9F), median age 59.5, with 3 at 0.06 mg/kg, 4 at 0.09 mg/kg, and 5 at 0.12 mg/kg. There were no DLTs. There was a delayed infusion-related reaction with muscle aches, headache, and pyrexia. One patient at the 0.06 mg/kg dose level had a partial response (PR) and no progression for more than 32 months. Two other patients had stable disease (SD) for 22 and 9 months before disease progression.</div></div><div><h3>Conclusion</h3><div>Among the 12 patients treated with escalating doses of quaratusugene ozeplasmid and standard doses of osimertinib there were 3 patients with prolonged time to progression, including 1 with continuing PR. Quaratusugene ozeplasmid administration was associated with a delayed infusion-related reaction managed with prophylactic steroids, acetaminophen and diphenhydramine. There were no DLTs. The recommended phase II dose of quaratusugene ozeplasmid in combination with osimertinib in patients with NSCLC progressing after osimertinib treatment is 0.12 mg/kg.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 1","pages":"Pages 75-81"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732955","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}
Pub Date : 2026-01-01Epub Date: 2025-10-22DOI: 10.1016/j.cllc.2025.10.014
Khalil Choucair , Hyejeong Jang , Shadia I Jalal , Tarik Hadid , Dipesh Uprety , Seongho Kim , Hirva Mamdani
Introduction
Immune checkpoint inhibitors (IO) are widely used in treating advanced non–small cell lung cancer (NSCLC). Historically, patients with squamous cell carcinoma (SCC) had poorer survival than those with nonsquamous (nSCC) histology, but the impact of histology on IO efficacy is underexplored. We conducted a systematic review and meta-analysis to compare survival outcomes between SCC and nSCC NSCLC patients treated with IO.
Methods
Following PRISMA guidelines, we searched PubMed, EMBASE, and abstracts from ASCO and ESMO (January 1, 2010-December 31, 2022). Eligible studies were phase II/III randomized controlled trials evaluating IO in NSCLC patients with defined histologic subtypes and available hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS). We pooled HRs to estimate the ratio of HRs (RHR) for OS and PFS. Study quality was assessed using the Cochrane Risk of Bias (RoB) tool.
Results
Out of 6220 identified records, 23 studies including 14,171 patients were analyzed. No significant differences were observed in OS (RHR 1.06; P = .406) or PFS (RHR 1.09; P = .506) between SCC and nSCC, regardless of therapy line or IO regimen (monotherapy vs. chemo-IO). Subgroup analysis showed no differences based on PD-L1 status. Within each histology, outcomes were also similar between PD-L1+ and PD-L1− patients.
Conclusion
IO efficacy in NSCLC appears independent of histology and PD-L1 status. Although SCC patients previously had worse outcomes, IO therapy may have helped bridge the survival gap between SCC and nSCC patients, by leveraging a shared antitumor immune response mechanism.
免疫检查点抑制剂（IO）广泛用于治疗晚期非小细胞肺癌（NSCLC）。从历史上看，鳞状细胞癌（SCC）患者的生存率低于非鳞状细胞癌（nSCC）患者，但组织学对IO疗效的影响尚未得到充分探讨。我们进行了一项系统回顾和荟萃分析，比较了接受IO治疗的SCC和NSCLC患者的生存结果。方法按照PRISMA指南，检索PubMed、EMBASE以及ASCO和ESMO的摘要（2010年1月1日- 2022年12月31日）。符合条件的研究是II/III期随机对照试验，评估具有明确组织学亚型的NSCLC患者的IO，以及无进展生存期（PFS）和总生存期（OS）的可用风险比（HR）。我们汇总hr以估计OS和PFS的hr （RHR）之比。使用Cochrane风险偏倚（RoB）工具评估研究质量。结果在6220份确定的记录中，分析了23项研究，包括14171名患者。无论何种治疗线或IO方案（单药vs化疗-IO）， SCC和nSCC之间的OS （RHR 1.06; P = .406）或PFS （RHR 1.09; P = .506）均无显著差异。亚组分析显示PD-L1状态无差异。在每种组织学中，PD-L1+和PD-L1−患者的结果也相似。结论io治疗非小细胞肺癌的疗效与组织学和PD-L1状态无关。尽管SCC患者先前的预后较差，但通过利用共享的抗肿瘤免疫反应机制，IO治疗可能有助于弥合SCC和非SCC患者之间的生存差距。
{"title":"Impact of Histology and PD-L1 Status on Immune Checkpoint Inhibitors in the Treatment of Non–Small Cell Lung Cancer a Systemic Review and Meta-analysis","authors":"Khalil Choucair , Hyejeong Jang , Shadia I Jalal , Tarik Hadid , Dipesh Uprety , Seongho Kim , Hirva Mamdani","doi":"10.1016/j.cllc.2025.10.014","DOIUrl":"10.1016/j.cllc.2025.10.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Immune checkpoint inhibitors (IO) are widely used in treating advanced non–small cell lung cancer (NSCLC). Historically, patients with squamous cell carcinoma (SCC) had poorer survival than those with nonsquamous (nSCC) histology, but the impact of histology on IO efficacy is underexplored. We conducted a systematic review and meta-analysis to compare survival outcomes between SCC and nSCC NSCLC patients treated with IO.</div></div><div><h3>Methods</h3><div>Following PRISMA guidelines, we searched PubMed, EMBASE, and abstracts from ASCO and ESMO (January 1, 2010-December 31, 2022). Eligible studies were phase II/III randomized controlled trials evaluating IO in NSCLC patients with defined histologic subtypes and available hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS). We pooled HRs to estimate the ratio of HRs (RHR) for OS and PFS. Study quality was assessed using the Cochrane Risk of Bias (RoB) tool.</div></div><div><h3>Results</h3><div>Out of 6220 identified records, 23 studies including 14,171 patients were analyzed. No significant differences were observed in OS (RHR 1.06; <em>P</em> = .406) or PFS (RHR 1.09; <em>P</em> = .506) between SCC and nSCC, regardless of therapy line or IO regimen (monotherapy vs. chemo-IO). Subgroup analysis showed no differences based on PD-L1 status. Within each histology, outcomes were also similar between PD-L1+ and PD-L1− patients.</div></div><div><h3>Conclusion</h3><div>IO efficacy in NSCLC appears independent of histology and PD-L1 status. Although SCC patients previously had worse outcomes, IO therapy may have helped bridge the survival gap between SCC and nSCC patients, by leveraging a shared antitumor immune response mechanism.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 1","pages":"Pages 1-12"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145555409","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}
Pub Date : 2026-01-01Epub Date: 2025-11-19DOI: 10.1016/j.cllc.2025.11.013
Byoung Chul Cho , YuKyung Kim
{"title":"Response to the Letter to the Editor: “Lazertinib in EGFR-Mutated NSCLC with CNS Metastases: Reinforcing the Role of Third-Generation TKIs through Pooled Analysis”","authors":"Byoung Chul Cho , YuKyung Kim","doi":"10.1016/j.cllc.2025.11.013","DOIUrl":"10.1016/j.cllc.2025.11.013","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 1","pages":"Pages 72-73"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713567","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}
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