Pub Date : 2025-12-05DOI: 10.1016/j.cllc.2025.11.020
Jiawen Sun , Xin Dong , Zhixue Fu , Sen Han , Yuliang Liu , Anhui Shi , Huiming Yu , Yuting Zhao , Wei Deng , Leilei Jiang , Dan Yang , Xiao Chang , Liuhua Long , Jiayi Yu , Yue Teng , Rong Yu , Weihu Wang
Objectives
This study assessed the impact of immune checkpoint inhibitors (ICIs) addition and timing on the incidence of treatment-related pneumonitis (TRP) and explored type-specific risk factors in unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving definitive chemoradiotherapy (CRT).
Methods
We retrospectively analyzed 449 LA-NSCLC patients receiving definitive CRT±ICIs from January 2019 to December 2021. Patients were grouped by CRT alone (n = 236) or CRT+ICIs (n = 213), with the latter stratified by ICIs timing (induction/concurrent/consolidation) relative to radiotherapy. TRP (including radiation pneumonitis [RP] and checkpoint inhibitor pneumonitis [CIP]) was graded per CTCAE v5.0 through multidisciplinary review. We applied inverse probability of treatment weighting (IPTW) to adjust baseline covariates, Fine-Gray competing-risk model to estimate cumulative incidence and risk factors.
Results
Grade ≥ 2 TRP incidence was significantly increased with CRT+ICIs than CRT (30.6% vs. 9.8%; IPTW-adjusted P < .001), highest with concurrent ICIs (51.5%), followed by induction (32.0%) and consolidation (24.2%). Grade ≥ 2 RP increased to 16.7% with ICIs (IPTW-adjusted P = .004), peaking in the concurrent subgroup (39.1%), while comparable between induction and consolidation (16.1% vs. 12.2%). Independent predictors of grade ≥ 2 RP included ICIs treatment, gemcitabine-based induction chemotherapy, and higher lung dosimetry, with cut-offs of lung V20 (volume receiving ≥ 20 Gy) = 26.8% and mean lung dose (MLD) = 14.05 Gy. Grade ≥ 2 CIP incidence (14.2%) was associated with pre-existing interstitial lung disease or emphysema, PD-1 inhibitors and elevated MLD.
Conclusions
ICIs addition and timing significantly affected TRP risk. Mitigating lung toxicity requires careful selection of ICIs strategy, chemotherapy agents, and optimizing lung radiation dosimetry.
{"title":"Cumulative Incidence and Type-Specific Risk Factors of Pneumonitis After Definitive Chemoradiotherapy With or Without Immunotherapy in Locally Advanced Non-Small Cell Lung Cancer","authors":"Jiawen Sun , Xin Dong , Zhixue Fu , Sen Han , Yuliang Liu , Anhui Shi , Huiming Yu , Yuting Zhao , Wei Deng , Leilei Jiang , Dan Yang , Xiao Chang , Liuhua Long , Jiayi Yu , Yue Teng , Rong Yu , Weihu Wang","doi":"10.1016/j.cllc.2025.11.020","DOIUrl":"10.1016/j.cllc.2025.11.020","url":null,"abstract":"<div><h3>Objectives</h3><div>This study assessed the impact of immune checkpoint inhibitors (ICIs) addition and timing on the incidence of treatment-related pneumonitis (TRP) and explored type-specific risk factors in unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving definitive chemoradiotherapy (CRT).</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 449 LA-NSCLC patients receiving definitive CRT±ICIs from January 2019 to December 2021. Patients were grouped by CRT alone (<em>n</em> = 236) or CRT+ICIs (<em>n</em> = 213), with the latter stratified by ICIs timing (induction/concurrent/consolidation) relative to radiotherapy. TRP (including radiation pneumonitis [RP] and checkpoint inhibitor pneumonitis [CIP]) was graded per CTCAE v5.0 through multidisciplinary review. We applied inverse probability of treatment weighting (IPTW) to adjust baseline covariates, Fine-Gray competing-risk model to estimate cumulative incidence and risk factors.</div></div><div><h3>Results</h3><div>Grade ≥ 2 TRP incidence was significantly increased with CRT+ICIs than CRT (30.6% vs. 9.8%; IPTW-adjusted <em>P</em> < .001), highest with concurrent ICIs (51.5%), followed by induction (32.0%) and consolidation (24.2%). Grade ≥ 2 RP increased to 16.7% with ICIs (IPTW-adjusted <em>P</em> = .004), peaking in the concurrent subgroup (39.1%), while comparable between induction and consolidation (16.1% vs. 12.2%). Independent predictors of grade ≥ 2 RP included ICIs treatment, gemcitabine-based induction chemotherapy, and higher lung dosimetry, with cut-offs of lung V20 (volume receiving ≥ 20 Gy) = 26.8% and mean lung dose (MLD) = 14.05 Gy. Grade ≥ 2 CIP incidence (14.2%) was associated with pre-existing interstitial lung disease or emphysema, PD-1 inhibitors and elevated MLD.</div></div><div><h3>Conclusions</h3><div>ICIs addition and timing significantly affected TRP risk. Mitigating lung toxicity requires careful selection of ICIs strategy, chemotherapy agents, and optimizing lung radiation dosimetry.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 14-24"},"PeriodicalIF":3.3,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924420","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 : 2025-12-04DOI: 10.1016/j.cllc.2025.11.019
Yuting Kuang , Ke Zu , Dezhi Xing , Aixue Liu , Jennifer Uyei , Arianna Nevo , Hsiu-Ching Chang , Christine M. Pierce
Pneumonitis is a notable toxicity of lung cancer therapies, particularly radiation and immune checkpoint inhibitors. Racial and ethnic disparities in pneumonitis risk exist, yet heterogeneity remains understudied. This study aimed to quantify pneumonitis incidence among East and Southeast Asian patients treated for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A systematic literature review (SLR) and single-arm meta-analysis were conducted following Cochrane and PRISMA guidelines. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and 5 local language databases were searched for studies published from January 1, 2014 to August 2, 2023. Included were clinical trials in Asian patients undergoing pharmacological or radiation therapy for NSCLC or SCLC. The SLR included 218 trials (NSCLC: 202, SCLC: 16). Pooled incidence of all-grade, grade 1 to 2, and grade 3 to 5 pneumonitis in NSCLC was 5.42% (95% CI, 4.25-6.89), 3.58% (95% CI, 2.54-5.03) and 1.34% (95% CI, 1.06-1.70), respectively. For SCLC, pooled incidence was 12.21% (95% CI, 4.77-27.85), 7.64% (95% CI, 2.48-21.23), and 2.43% (95% CI, 1.47-3.97), respectively. Significantly higher rates of pneumonitis were observed in patients receiving chemoradiation or radiation-containing treatments, in general, compared to those not treated with radiation; grade 3 to 5 events in SCLC were not significantly different. This study establishes baseline pneumonitis risk in East and Southeast Asian patients treated for NSCLC and SCLC, highlighting higher incidence in those receiving radiation-containing treatments, particularly for lower-grade events. The results help contextualize safety data from clinical trials enrolling Asian patients.
{"title":"Incidence of Pneumonitis in Asian Patients With Lung Cancer: A Systematic Literature Review and Meta-analysis","authors":"Yuting Kuang , Ke Zu , Dezhi Xing , Aixue Liu , Jennifer Uyei , Arianna Nevo , Hsiu-Ching Chang , Christine M. Pierce","doi":"10.1016/j.cllc.2025.11.019","DOIUrl":"10.1016/j.cllc.2025.11.019","url":null,"abstract":"<div><div>Pneumonitis is a notable toxicity of lung cancer therapies, particularly radiation and immune checkpoint inhibitors. Racial and ethnic disparities in pneumonitis risk exist, yet heterogeneity remains understudied. This study aimed to quantify pneumonitis incidence among East and Southeast Asian patients treated for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A systematic literature review (SLR) and single-arm meta-analysis were conducted following Cochrane and PRISMA guidelines. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and 5 local language databases were searched for studies published from January 1, 2014 to August 2, 2023. Included were clinical trials in Asian patients undergoing pharmacological or radiation therapy for NSCLC or SCLC. The SLR included 218 trials (NSCLC: 202, SCLC: 16). Pooled incidence of all-grade, grade 1 to 2, and grade 3 to 5 pneumonitis in NSCLC was 5.42% (95% CI, 4.25-6.89), 3.58% (95% CI, 2.54-5.03) and 1.34% (95% CI, 1.06-1.70), respectively. For SCLC, pooled incidence was 12.21% (95% CI, 4.77-27.85), 7.64% (95% CI, 2.48-21.23), and 2.43% (95% CI, 1.47-3.97), respectively. Significantly higher rates of pneumonitis were observed in patients receiving chemoradiation or radiation-containing treatments, in general, compared to those not treated with radiation; grade 3 to 5 events in SCLC were not significantly different. This study establishes baseline pneumonitis risk in East and Southeast Asian patients treated for NSCLC and SCLC, highlighting higher incidence in those receiving radiation-containing treatments, particularly for lower-grade events. The results help contextualize safety data from clinical trials enrolling Asian patients.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 25-37"},"PeriodicalIF":3.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975196","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 : 2025-12-02DOI: 10.1016/j.cllc.2025.11.018
Utsav Joshi , Faustine Ong , Daniel Melzer , Joanna C. Ma , Andreas Saltos , Alberto Chiappori , Benjamin Creelan , Bruna Pellini , Charles Lu , Eric Haura , Michael Shafique , Tawee Tanvetyanon , Syeda Saba Kareem , Pravash Budhathoki , Daniela C. Bravo Solarte , Syeda Mahrukh Hussnain Naqvi , Omar Castaneda Puglianini , Sameh Gaballa , Jhanelle E. Gray , Sonam Puri
Purpose
Tarlatamab, a DLL3-targeted bispecific T-cell engager, has emerged as a second-line therapy for extensive-stage small cell lung cancer (ES-SCLC) following progression on platinum-based chemoimmunotherapy. While clinical trials have demonstrated promising efficacy, real-world data on safety remain limited.
Methods
This retrospective study included 40 patients with SCLC or high-grade neuroendocrine carcinoma treated with tarlatamab at Moffitt Cancer Center between May 2024 and February 2025. Clinical, laboratory, and treatment-related variables including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reviewed. Predictive models for these toxicities were developed using Firth logistic regression based on data from 30 patients who did not receive prophylactic tocilizumab.
Results
The median age was 66.5 years; 55% were male, and 87.5% had an ECOG performance status of 0 to 1. Among patients who did not receive prophylactic tocilizumab (N = 30), 53.3% developed CRS and 23.3% developed ICANS after Cycle 1 Day 1, with 10% experiencing grade ≥ 3 severity for each. Three patients discontinued treatment due to severe CRS/ICANS, with 2 deaths and 1 transition to hospice. Among those who received prophylactic tocilizumab (N = 10), 1 patient developed grade 2 CRS and none developed ICANS. Elevated LDH and liver metastasis were independent predictors of CRS; LDH was also predictive of grade ≥ 2 CRS. Diabetes and cardiovascular disease were independently associated with ICANS.
Conclusion
Tarlatamab is associated with higher CRS and ICANS rates in real-world settings than observed in trials. Prophylactic tocilizumab may mitigate these toxicities in high-risk patients and should be considered for incorporation into treatment protocols.
{"title":"Optimizing Tarlatamab Delivery in Small Cell and Neuroendocrine Lung Cancer: Real-World Insights into Step-Up Dosing and Prophylactic Tocilizumab Use","authors":"Utsav Joshi , Faustine Ong , Daniel Melzer , Joanna C. Ma , Andreas Saltos , Alberto Chiappori , Benjamin Creelan , Bruna Pellini , Charles Lu , Eric Haura , Michael Shafique , Tawee Tanvetyanon , Syeda Saba Kareem , Pravash Budhathoki , Daniela C. Bravo Solarte , Syeda Mahrukh Hussnain Naqvi , Omar Castaneda Puglianini , Sameh Gaballa , Jhanelle E. Gray , Sonam Puri","doi":"10.1016/j.cllc.2025.11.018","DOIUrl":"10.1016/j.cllc.2025.11.018","url":null,"abstract":"<div><h3>Purpose</h3><div>Tarlatamab, a DLL3-targeted bispecific T-cell engager, has emerged as a second-line therapy for extensive-stage small cell lung cancer (ES-SCLC) following progression on platinum-based chemoimmunotherapy. While clinical trials have demonstrated promising efficacy, real-world data on safety remain limited.</div></div><div><h3>Methods</h3><div>This retrospective study included 40 patients with SCLC or high-grade neuroendocrine carcinoma treated with tarlatamab at Moffitt Cancer Center between May 2024 and February 2025. Clinical, laboratory, and treatment-related variables including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reviewed. Predictive models for these toxicities were developed using Firth logistic regression based on data from 30 patients who did not receive prophylactic tocilizumab.</div></div><div><h3>Results</h3><div>The median age was 66.5 years; 55% were male, and 87.5% had an ECOG performance status of 0 to 1. Among patients who did not receive prophylactic tocilizumab (N = 30), 53.3% developed CRS and 23.3% developed ICANS after Cycle 1 Day 1, with 10% experiencing grade ≥ 3 severity for each. Three patients discontinued treatment due to severe CRS/ICANS, with 2 deaths and 1 transition to hospice. Among those who received prophylactic tocilizumab (N = 10), 1 patient developed grade 2 CRS and none developed ICANS. Elevated LDH and liver metastasis were independent predictors of CRS; LDH was also predictive of grade ≥ 2 CRS. Diabetes and cardiovascular disease were independently associated with ICANS.</div></div><div><h3>Conclusion</h3><div>Tarlatamab is associated with higher CRS and ICANS rates in real-world settings than observed in trials. Prophylactic tocilizumab may mitigate these toxicities in high-risk patients and should be considered for incorporation into treatment protocols.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 2","pages":"Pages 48-58"},"PeriodicalIF":3.3,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975194","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 : 2025-11-27DOI: 10.1016/j.cllc.2025.11.010
Huiyang Shi, Haohua Zhu, Le Tang, Jingyu Lu, Kai Zhu, Miaohan Wang, Xingsheng Hu, Yuankai Shi
Background: This single-arm, phase I/II trial aimed to evaluate the efficacy and safety of firmonertinib plus anlotinib as first-line treatment for patients with non small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.
Methods: We enrolled patients aged 18 years or older and had locally advanced or metastatic NSCLC harboring EGFR sensitive mutation. Patients were treated with oral firmonertinib 80 mg once daily combined with oral anlotinib (days 1-14 in 21-day cycle). The primary endpoint was objective response rate (ORR).
Results: Between March, 19th, 2022 and July, 27th, 2023, 36 patients were enrolled. In dose-exploration phase, 2 patients were treated with anlotinib 8 mg, 3 were treated with anlotinib 10 mg and 3 were treated with anlotinib 12 mg combined with firmonertinib 80 mg. In dose-expansion phase, 5 were treated with 10 mg anlotinib and 23 were treated with anlotinib 12 mg combined with firmonertinib 80 mg. The median follow-up time was 19.4 months. ORR was 63.9% and disease control rate (DCR) was 100.0%. Median progression free survival (PFS) was 19.6 months (95% CI 16.9-22.3). Median duration of response (DoR) was 23.0 months (95% CI 12.1-34.0). Concurrent pathogenic TP53 mutation was an independent prognostic factor (HR 2.38, 95% CI 0.90-6.30, P = .07). Diarrhea and hypertension were the most common TRAEs. ≥Grade 3 TRAEs occured in 36.1% patients. 47.2% patients experienced dose reduction and 33.3% patients experienced treatment discontinuation.
Conclusion: Firmonertinib plus anlotinib demonstrated preliminary efficacy and manageable safety as first-line treatment among patients with NSCLC harboring EGFR mutations.
背景：这项单组I/II期临床试验旨在评估firmonertinib联合anlotinib作为表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者一线治疗的有效性和安全性。方法：我们招募了18岁或以上的局部晚期或转移性非小细胞肺癌患者，这些患者携带EGFR敏感突变。患者口服firmonertinib 80mg，每日1次，联合口服anlotinib（第1-14天，21天周期）。主要终点为客观缓解率（ORR）。结果：2022年3月19日至2023年7月27日，共纳入36例患者。在剂量探索阶段，2例患者接受安洛替尼8mg治疗，3例患者接受安洛替尼10mg治疗，3例患者接受安洛替尼12mg联合菲莫替尼80mg治疗。在剂量膨胀期，5人用10mg安洛替尼治疗，23人用12mg安洛替尼联合80mg菲莫替尼治疗。中位随访时间为19.4个月。ORR为63.9%，疾病控制率为100.0%。中位无进展生存期（PFS）为19.6个月（95% CI 16.9-22.3）。中位反应持续时间（DoR）为23.0个月（95% CI 12.1-34.0）。并发致病性TP53突变是独立的预后因素（HR 2.38, 95% CI 0.90-6.30, P = 0.07）。腹泻和高血压是最常见的TRAEs。≥3级trae发生率为36.1%。47.2%的患者减量，33.3%的患者停药。结论：Firmonertinib + anlotinib作为EGFR突变NSCLC患者的一线治疗具有初步疗效和可管理的安全性。
{"title":"Efficacy and Safety of Firmonertinib Plus Anlotinib as First-Line Treatment for Advanced NSCLC With EGFR Mutations: A Single-Arm, Phase I/II Trial.","authors":"Huiyang Shi, Haohua Zhu, Le Tang, Jingyu Lu, Kai Zhu, Miaohan Wang, Xingsheng Hu, Yuankai Shi","doi":"10.1016/j.cllc.2025.11.010","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.11.010","url":null,"abstract":"<p><strong>Background: </strong>This single-arm, phase I/II trial aimed to evaluate the efficacy and safety of firmonertinib plus anlotinib as first-line treatment for patients with non small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.</p><p><strong>Methods: </strong>We enrolled patients aged 18 years or older and had locally advanced or metastatic NSCLC harboring EGFR sensitive mutation. Patients were treated with oral firmonertinib 80 mg once daily combined with oral anlotinib (days 1-14 in 21-day cycle). The primary endpoint was objective response rate (ORR).</p><p><strong>Results: </strong>Between March, 19th, 2022 and July, 27th, 2023, 36 patients were enrolled. In dose-exploration phase, 2 patients were treated with anlotinib 8 mg, 3 were treated with anlotinib 10 mg and 3 were treated with anlotinib 12 mg combined with firmonertinib 80 mg. In dose-expansion phase, 5 were treated with 10 mg anlotinib and 23 were treated with anlotinib 12 mg combined with firmonertinib 80 mg. The median follow-up time was 19.4 months. ORR was 63.9% and disease control rate (DCR) was 100.0%. Median progression free survival (PFS) was 19.6 months (95% CI 16.9-22.3). Median duration of response (DoR) was 23.0 months (95% CI 12.1-34.0). Concurrent pathogenic TP53 mutation was an independent prognostic factor (HR 2.38, 95% CI 0.90-6.30, P = .07). Diarrhea and hypertension were the most common TRAEs. ≥Grade 3 TRAEs occured in 36.1% patients. 47.2% patients experienced dose reduction and 33.3% patients experienced treatment discontinuation.</p><p><strong>Conclusion: </strong>Firmonertinib plus anlotinib demonstrated preliminary efficacy and manageable safety as first-line treatment among patients with NSCLC harboring EGFR mutations.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917201","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 : 2025-11-22DOI: 10.1016/j.cllc.2025.11.017
Charu Aggarwal , Sophia Ng , Rajesh Kamalakar , Sue Beruti , Archana Simmons , Mary Beth Beasley
Background
Comprehensive biomarker testing for patients with advanced/metastatic non-small cell lung cancer (a/mNSCLC) is essential for treatment decision-making. However, there is limited understanding of testing adoption across lines of therapy (LoT).
Materials and Methods
This retrospective real-world study used the ConcertAI Patient360™ NSCLC database in the US to assess biomarker testing patterns among adults with nonsquamous a/mNSCLC (2017-2022) who received ≥ 1 LoT with ≥ 90-day follow-up. Testing and rebiopsy rates for actionable biomarkers were analyzed by LoT (1L, 2L, 3L), test modality, and sample type.
Results
Of 4528 patients, 51% were female, 76% were White; the mean (SD) age at diagnosis was 67.2 (10.2) years. Testing rates for ≥ 1 biomarker were 85% (1L), 31% (2L), and 26% (3L). 1L IHC and 1L NGS testing rates were 52% and 57%, respectively (2017-2022). Tissue was tested most often in 1L; liquid biopsy was prioritized in 2L. Among patients who received corresponding LoT and any biomarker test for the prior line, Black patients had lower crude rates of 2L rebiopsy and male patients had significantly lower rates of 2L rebiopsy/testing. Adjusted odds ratio (95% CI) for rebiopsy was lower for patients with EGFR WT versus EGFR mutation at 2L (0.40 [0.28-0.59]; P < .001) and 3L (0.46 [0.24-0.89]; P = .020).
Conclusions
While tissue was most frequently used in 1L testing, rebiopsy was less frequent in 2L + . Racial and sex differences in rebiopsy/testing rates were observed. Standardization for 2L + biomarker testing is needed to optimize later-line treatment decisions for patients with a/mNSCLC.
{"title":"A United States-Based Real-World Study on Biomarker Testing and Rebiopsy Rates Among Patients With Non-Small Cell Lung Cancer Across Lines of Therapy","authors":"Charu Aggarwal , Sophia Ng , Rajesh Kamalakar , Sue Beruti , Archana Simmons , Mary Beth Beasley","doi":"10.1016/j.cllc.2025.11.017","DOIUrl":"10.1016/j.cllc.2025.11.017","url":null,"abstract":"<div><h3>Background</h3><div>Comprehensive biomarker testing for patients with advanced/metastatic non-small cell lung cancer (a/mNSCLC) is essential for treatment decision-making. However, there is limited understanding of testing adoption across lines of therapy (LoT).</div></div><div><h3>Materials and Methods</h3><div>This retrospective real-world study used the ConcertAI Patient360™ NSCLC database in the US to assess biomarker testing patterns among adults with nonsquamous a/mNSCLC (2017-2022) who received ≥ 1 LoT with ≥ 90-day follow-up. Testing and rebiopsy rates for actionable biomarkers were analyzed by LoT (1L, 2L, 3L), test modality, and sample type.</div></div><div><h3>Results</h3><div>Of 4528 patients, 51% were female, 76% were White; the mean (SD) age at diagnosis was 67.2 (10.2) years. Testing rates for ≥ 1 biomarker were 85% (1L), 31% (2L), and 26% (3L). 1L IHC and 1L NGS testing rates were 52% and 57%, respectively (2017-2022). Tissue was tested most often in 1L; liquid biopsy was prioritized in 2L. Among patients who received corresponding LoT and any biomarker test for the prior line, Black patients had lower crude rates of 2L rebiopsy and male patients had significantly lower rates of 2L rebiopsy/testing. Adjusted odds ratio (95% CI) for rebiopsy was lower for patients with <em>EGFR</em> WT versus <em>EGFR</em> mutation at 2L (0.40 [0.28-0.59]; <em>P</em> < .001) and 3L (0.46 [0.24-0.89]; <em>P</em> = .020).</div></div><div><h3>Conclusions</h3><div>While tissue was most frequently used in 1L testing, rebiopsy was less frequent in 2L + . Racial and sex differences in rebiopsy/testing rates were observed. Standardization for 2L + biomarker testing is needed to optimize later-line treatment decisions for patients with a/mNSCLC.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"27 1","pages":"Pages 82-91"},"PeriodicalIF":3.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827054","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}
Background: HER2 overexpression is defined as immunohistochemistry (IHC) 2+/3+, and trastuzumab deruxtecan (T-DXd) is approved for treating unresectable or metastatic solid tumors with HER2 3+. HER2 spatiotemporal heterogeneity is crucial for identifying patients responsive to T-DXd. While extensively studied in gastric and breast cancers, research in non-small cell lung cancer (NSCLC) is limited. We aim to examine HER2 expression and their implications for optimizing specimen selection in potential T-DXd beneficiaries.
Materials and methods: We retrospectively collected NSCLC cases from Peking University Cancer Hospital (2015-2024) with HER2 testing, matched specimens (resection vs. biopsy; primary vs. metastasis), at least 1 lesion with HER2 2+ or 3+. Two pathologists independently re-evaluated enrolled cases using gastric cancer criteria.
Results: A total of 5211 cases underwent HER2 testing, with 2+ expression in 773 (14.8%) and 3+ in 35 (0.7%) cases. Ultimately, 129 patients met inclusion criteria, comprising 88 surgical/biopsy and 102 primary/metastatic samples. Concordance between biopsy and resection was 51.4% (38/74) for HER2 2+ and 21.4% (3/14) for HER2 3+, with significantly higher concordance for 2+ (P = .040). Concordance was 39.4% (28/85) for HER2 2+ and 35.4% (5/14) for HER2 3+ in primary vs metastatic tumors, with no significant difference between lymph node and distant metastases. Both biopsy and metastatic samples underestimated HER2 2+ and 3+ expression.
Conclusions: Our study demonstrates that in potential NSCLC beneficiaries of T-DXd therapy, HER2 expression is underestimated in biopsy samples and metastatic lesions compared to resected and primary sites. This heterogeneity holds great significance for guiding clinical sample selection.
{"title":"A Comprehensive Analysis of HER2 status Heterogeneity Using Matched Samples among Potential Beneficiaries of Trastuzumab Deruxtecan Therapy in Non-Small Cell Lung Cancer.","authors":"Haiyue Wang, Wei Sun, Chenglong Wang, Xin Yang, Kaiwen Chi, Xinying Liu, Xiaozheng Huang, Lixin Zhou, Dongmei Lin","doi":"10.1016/j.cllc.2025.11.015","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.11.015","url":null,"abstract":"<p><strong>Background: </strong>HER2 overexpression is defined as immunohistochemistry (IHC) 2+/3+, and trastuzumab deruxtecan (T-DXd) is approved for treating unresectable or metastatic solid tumors with HER2 3+. HER2 spatiotemporal heterogeneity is crucial for identifying patients responsive to T-DXd. While extensively studied in gastric and breast cancers, research in non-small cell lung cancer (NSCLC) is limited. We aim to examine HER2 expression and their implications for optimizing specimen selection in potential T-DXd beneficiaries.</p><p><strong>Materials and methods: </strong>We retrospectively collected NSCLC cases from Peking University Cancer Hospital (2015-2024) with HER2 testing, matched specimens (resection vs. biopsy; primary vs. metastasis), at least 1 lesion with HER2 2+ or 3+. Two pathologists independently re-evaluated enrolled cases using gastric cancer criteria.</p><p><strong>Results: </strong>A total of 5211 cases underwent HER2 testing, with 2+ expression in 773 (14.8%) and 3+ in 35 (0.7%) cases. Ultimately, 129 patients met inclusion criteria, comprising 88 surgical/biopsy and 102 primary/metastatic samples. Concordance between biopsy and resection was 51.4% (38/74) for HER2 2+ and 21.4% (3/14) for HER2 3+, with significantly higher concordance for 2+ (P = .040). Concordance was 39.4% (28/85) for HER2 2+ and 35.4% (5/14) for HER2 3+ in primary vs metastatic tumors, with no significant difference between lymph node and distant metastases. Both biopsy and metastatic samples underestimated HER2 2+ and 3+ expression.</p><p><strong>Conclusions: </strong>Our study demonstrates that in potential NSCLC beneficiaries of T-DXd therapy, HER2 expression is underestimated in biopsy samples and metastatic lesions compared to resected and primary sites. This heterogeneity holds great significance for guiding clinical sample selection.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755430","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 : 2025-11-21DOI: 10.1016/j.cllc.2025.11.014
Yahya Alwatari, Robert A Vierkant, Matthew J Aizpuru, Sahar A Saddoughi, Carlos A Puig, Janani S Reisenauer, K Robert Shen, Stephen D Cassivi, Dennis A Wigle, Luis F Tapias
Objective: Identification of regional lymph node involvement has an impact on prognosis and treatment after surgery for clinical stage IA1-2 non-small cell lung cancer (NSCLC). This study investigates nodal upstaging rates and associated factors, with a focus on sublobar resections.
Methods: The National Cancer Database (NCDB) was used to identify NSCLC patients with clinical T1a-b (≤ 2 cm), N0, M0 disease (stage IA1-2) who had sublobar resection or lobectomy from 2004 to 2021. Rates of nodal upstaging (cN0→pN+) were calculated over the study period according to the type of pulmonary resection. Factors associated with nodal upstaging were evaluated with multivariable logistic regression.
Results: The study included 58,626 patients. Nodal upstaging occurred in 6.4% of patients: 3.8% to pN1, 2.7% to pN2. Factors associated with nodal upstaging included male gender, larger tumor size, histology, higher tumor grade, positive resection margins, more regional lymph nodes examined, and type of pulmonary resection. Nodal upstaging rates were 2.9% for wedge resections, 3.7% for segmentectomies, and 8.3% for lobectomies (P < .001). Compared to lobectomy, sublobar resections had lower odds of nodal upstaging: wedge resection (adjusted OR 0.58, 95% CI, 0.51-0.65) and segmentectomy (adjusted OR 0.59, 95% CI, 0.49-0.70; P < .001). This gap in nodal upstaging between sublobar resections and lobectomy persisted over the study period.
Conclusions: The extent of surgical resection and lymph node evaluation were independent factors in detecting patients with regional lymph node involvement, signaling more advanced disease. As sublobar resections establish themselves as a widespread, valid treatment, strategies to close the gap in the detection of nodal disease are needed.
{"title":"Impact of Pulmonary Resection Extent on Nodal Upstaging in Clinical Stage IA1-2 NSCLC: Real-World Evidence of Low Detection Rates with Sublobar Resections.","authors":"Yahya Alwatari, Robert A Vierkant, Matthew J Aizpuru, Sahar A Saddoughi, Carlos A Puig, Janani S Reisenauer, K Robert Shen, Stephen D Cassivi, Dennis A Wigle, Luis F Tapias","doi":"10.1016/j.cllc.2025.11.014","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.11.014","url":null,"abstract":"<p><strong>Objective: </strong>Identification of regional lymph node involvement has an impact on prognosis and treatment after surgery for clinical stage IA1-2 non-small cell lung cancer (NSCLC). This study investigates nodal upstaging rates and associated factors, with a focus on sublobar resections.</p><p><strong>Methods: </strong>The National Cancer Database (NCDB) was used to identify NSCLC patients with clinical T1a-b (≤ 2 cm), N0, M0 disease (stage IA1-2) who had sublobar resection or lobectomy from 2004 to 2021. Rates of nodal upstaging (cN0→pN+) were calculated over the study period according to the type of pulmonary resection. Factors associated with nodal upstaging were evaluated with multivariable logistic regression.</p><p><strong>Results: </strong>The study included 58,626 patients. Nodal upstaging occurred in 6.4% of patients: 3.8% to pN1, 2.7% to pN2. Factors associated with nodal upstaging included male gender, larger tumor size, histology, higher tumor grade, positive resection margins, more regional lymph nodes examined, and type of pulmonary resection. Nodal upstaging rates were 2.9% for wedge resections, 3.7% for segmentectomies, and 8.3% for lobectomies (P < .001). Compared to lobectomy, sublobar resections had lower odds of nodal upstaging: wedge resection (adjusted OR 0.58, 95% CI, 0.51-0.65) and segmentectomy (adjusted OR 0.59, 95% CI, 0.49-0.70; P < .001). This gap in nodal upstaging between sublobar resections and lobectomy persisted over the study period.</p><p><strong>Conclusions: </strong>The extent of surgical resection and lymph node evaluation were independent factors in detecting patients with regional lymph node involvement, signaling more advanced disease. As sublobar resections establish themselves as a widespread, valid treatment, strategies to close the gap in the detection of nodal disease are needed.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721464","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 : 2025-11-19DOI: 10.1016/j.cllc.2025.11.011
Kasper Foged Guldbrandsen, Martin Bloch, Kristin Skougaard, Elisabeth Albrecht-Beste, Hanne Marie Nellemann, Martin Krakauer, Peter Michael Gørtz, Julie Marie Grüner, Joan Fledelius, Anne Lerberg Nielsen, Paw Christian Holdgaard, Søren Steen Nielsen, Karin Hjorthaug, Lise Barlebo Ahlborn, Erik Jakobsen, Anette Højsgaard, Rene Horsleben Petersen, Lars Borgbjerg Møller, Morten Dahl, Boe Sandahl Sorensen, Malene Støchkel Frank, Jeanette Haar Ehlers, Zaigham Saghir, Mette Pøhl, Svetlana Borissova, Lotte Holm Land, Charlotte Kristiansen, Tine McCulloch, Lise Saksø Mortensen, Malene Søby Christophersen, Ole Hilberg, Thor Lind Rasmussen, Signe Høyer Simonsen Schwaner, Christian B Laursen, Uffe Bodtger, Markus Nowak Lonsdale, Christian Niels Meyer, Oke Gerke, Jann Mortensen, Torben Riis Rasmussen, Barbara Malene Fischer
Background: Following curative treatment for non-small cell lung cancer (NSCLC), surveillance to detect recurrence is recommended. While computed tomography (CT) is the current standard for follow-up imaging, the optimal surveillance strategy remains debated. This study compares the diagnostic accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT; hereafter referred to as PET/CT) and CT for NSCLC surveillance.
Materials and methods: This study represents a secondary analysis of data from a randomized controlled trial (SUPE_R, ClinicalTrials.gov NCT03740126) of patients with stage IA-IIIC NSCLC who completed curative-intent treatment between February 2019 and February 2022. CT and PET/CT scans were compared for recurrence detection using biopsy, multidisciplinary team assessment, or follow-up imaging as reference standards.
Results: The analysis included 899 PET/CT scans and 852 CT scans from 692 patients (mean age 69 years ± 8 [SD]; 412 female). For detecting recurrence, PET/CT demonstrated a higher sensitivity (88% [95% CI, 80%-93%] vs. 62% [95% CI, 50%-73%]; P < .001) but lower specificity (89% [95% CI, 86%-91%] vs. 96% [95% CI, 94%-97%]; P < .001) compared to CT. PET/CT demonstrated a higher sensitivity compared to CT after treatment with chemoradiotherapy (100% [95% CI, 72%-100%] vs. 46% [95% CI, 19%-75%]; P = .006) and at 0 to 6 month after treatment (83% [95% CI, 63%-94%] vs. 41% [95% CI, 21%-65%]; P = .008).
Conclusion: The higher sensitivity of PET/CT, particularly after chemoradiotherapy and early post-treatment, suggests it may be particularly valuable in these high-risk scenarios. However, CT remains preferred for routine surveillance of low-risk patients given its superior specificity.
背景：对非小细胞肺癌（NSCLC）进行根治治疗后，建议进行监测以发现复发。虽然计算机断层扫描（CT）是目前随访成像的标准，但最佳监测策略仍存在争议。本研究比较了氟-18氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（[18F]FDG PET/CT，以下简称PET/CT）与CT在NSCLC监测中的诊断准确性。材料和方法：本研究对一项随机对照试验（super_r, ClinicalTrials.gov NCT03740126）的数据进行了二次分析，该试验纳入了2019年2月至2022年2月期间完成治愈意图治疗的IA-IIIC期NSCLC患者。采用活检、多学科团队评估或随访成像作为参考标准，比较CT和PET/CT扫描在复发检测方面的效果。结果：分析692例患者（平均年龄69岁±8岁[SD]；女性412例）的PET/CT扫描899张，CT扫描852张。对于检测复发，PET/CT表现出更高的敏感性（88% [95% CI, 80%-93%] vs. 62% [95% CI, 50%-73%]; P < .001），但特异性较低（89% [95% CI, 86%-91%] vs. 96% [95% CI, 94%-97%]; P < .001）。与放化疗后的CT相比，PET/CT显示出更高的敏感性（100% [95% CI, 72%-100%] vs. 46% [95% CI, 19%-75%]; P = 0.006）和治疗后0至6个月（83% [95% CI, 63%-94%] vs. 41% [95% CI, 21%-65%]; P = 0.008）。结论：PET/CT具有较高的敏感性，特别是在放化疗后和术后早期，提示其在这些高危病例中可能特别有价值。然而，鉴于其优越的特异性，CT仍然是低危患者常规监测的首选。
{"title":"Diagnostic Accuracy of [<sup>18</sup>F]FDG PET/CT versus CT for NSCLC Surveillance: Secondary Analysis of a Randomized Clinical Trial.","authors":"Kasper Foged Guldbrandsen, Martin Bloch, Kristin Skougaard, Elisabeth Albrecht-Beste, Hanne Marie Nellemann, Martin Krakauer, Peter Michael Gørtz, Julie Marie Grüner, Joan Fledelius, Anne Lerberg Nielsen, Paw Christian Holdgaard, Søren Steen Nielsen, Karin Hjorthaug, Lise Barlebo Ahlborn, Erik Jakobsen, Anette Højsgaard, Rene Horsleben Petersen, Lars Borgbjerg Møller, Morten Dahl, Boe Sandahl Sorensen, Malene Støchkel Frank, Jeanette Haar Ehlers, Zaigham Saghir, Mette Pøhl, Svetlana Borissova, Lotte Holm Land, Charlotte Kristiansen, Tine McCulloch, Lise Saksø Mortensen, Malene Søby Christophersen, Ole Hilberg, Thor Lind Rasmussen, Signe Høyer Simonsen Schwaner, Christian B Laursen, Uffe Bodtger, Markus Nowak Lonsdale, Christian Niels Meyer, Oke Gerke, Jann Mortensen, Torben Riis Rasmussen, Barbara Malene Fischer","doi":"10.1016/j.cllc.2025.11.011","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.11.011","url":null,"abstract":"<p><strong>Background: </strong>Following curative treatment for non-small cell lung cancer (NSCLC), surveillance to detect recurrence is recommended. While computed tomography (CT) is the current standard for follow-up imaging, the optimal surveillance strategy remains debated. This study compares the diagnostic accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT; hereafter referred to as PET/CT) and CT for NSCLC surveillance.</p><p><strong>Materials and methods: </strong>This study represents a secondary analysis of data from a randomized controlled trial (SUPE_R, ClinicalTrials.gov NCT03740126) of patients with stage IA-IIIC NSCLC who completed curative-intent treatment between February 2019 and February 2022. CT and PET/CT scans were compared for recurrence detection using biopsy, multidisciplinary team assessment, or follow-up imaging as reference standards.</p><p><strong>Results: </strong>The analysis included 899 PET/CT scans and 852 CT scans from 692 patients (mean age 69 years ± 8 [SD]; 412 female). For detecting recurrence, PET/CT demonstrated a higher sensitivity (88% [95% CI, 80%-93%] vs. 62% [95% CI, 50%-73%]; P < .001) but lower specificity (89% [95% CI, 86%-91%] vs. 96% [95% CI, 94%-97%]; P < .001) compared to CT. PET/CT demonstrated a higher sensitivity compared to CT after treatment with chemoradiotherapy (100% [95% CI, 72%-100%] vs. 46% [95% CI, 19%-75%]; P = .006) and at 0 to 6 month after treatment (83% [95% CI, 63%-94%] vs. 41% [95% CI, 21%-65%]; P = .008).</p><p><strong>Conclusion: </strong>The higher sensitivity of PET/CT, particularly after chemoradiotherapy and early post-treatment, suggests it may be particularly valuable in these high-risk scenarios. However, CT remains preferred for routine surveillance of low-risk patients given its superior specificity.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741490","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 : 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":"2025-11-19","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 : 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":"2025-11-19","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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