JTO Clinical and Research Reports最新文献

{"title":"Eftilagimod Alpha (a Soluble LAG-3 Protein) Combined With Pembrolizumab in Second-Line Metastatic NSCLC Refractory to Anti–Programmed Cell Death Protein 1/Programmed Death-Ligand 1-Based Therapy: Final Results from a Phase 2 Study","authors":"","doi":"10.1016/j.jtocrr.2024.100725","DOIUrl":"10.1016/j.jtocrr.2024.100725","url":null,"abstract":"<div><h3>Introduction</h3><div>Eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, triggers antigen-presenting cell and T-cell (CD4⁺ and CD8⁺) activation and helps overcome resistance to programmed cell death protein 1 or programmed cell death-ligand 1 (PD-(L)1) inhibitors. We assessed efti plus pembrolizumab in second-line anti–PD-(L)1-refractory metastatic patients with NSCLC.</div></div><div><h3>Methods</h3><div>After confirmed progression on anti-PD-(L)1-based first-line therapy, patients received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles and then every 3 weeks for up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary endpoint was the objective response rate by modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapies. Secondary endpoints included disease control rate, progression-free survival, overall survival (OS), and tolerability. Exploratory endpoints included tumor growth kinetics and predefined subgroup analyses. Programmed cell death-ligand 1 tumor proportion score was assessed centrally.</div></div><div><h3>Results</h3><div>Thirty-six patients were enrolled from April 2019 to August 2021 using Simon’s two-stage design. Most patients (81.8%) had low or negative (&lt;50%) PD-(L)1 tumor proportion score. First-line therapy was anti–PD-(L)1-based for all patients, combined with chemotherapy for 66.7%. The confirmed objective response and disease control rates were 8.3% and 33.3%. The median progression-free survival was 2.1 months and the median OS was 9.9 months. Patients exhibiting high PD-(L)1 expression or acquired resistance to PD-(L)1 inhibitors revealed superior response and survival outcomes, and OS was closely correlated with disease control. No treatment-emergent adverse event led to permanent discontinuation of study treatment.</div></div><div><h3>Conclusions</h3><div>Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-(L)1 inhibitors, warranting further investigation. Trial registration number: NCT03625323.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other Techniques in NSCLC","authors":"","doi":"10.1016/j.jtocrr.2024.100714","DOIUrl":"10.1016/j.jtocrr.2024.100714","url":null,"abstract":"<div><h3>Introduction</h3><div><em>RET</em> rearrangements occur in 1% to 2% NSCLCs. Since no clinically validated RET antibody is currently available, fluorescence in situ hybridization (FISH) is often used as a screening tool to identify patients likely to benefit from RET-targeted therapy. In this study, we performed a comprehensive review of publications in which <em>RET</em>-rearrangement testing was performed by FISH and compared the methods and results with our data.</div></div><div><h3>Methods</h3><div>The findings of an electronic search for publications using <em>RET</em>-FISH in lung cancer were compared with the results obtained at the Grenoble University Hospital where 784 <em>EGFR</em><em>-</em>, <em>KRAS</em><em>-</em>, <em>ALK</em>-, and <em>ROS1</em>-negative NSCLCs were tested by <em>RET</em> break-apart FISH and confirmed by RNA-sequencing (RNA-seq).</div></div><div><h3>Results</h3><div>Out of the 85 publications using <em>RET</em>-FISH analysis, 52 pertained to patients with lung cancer. The most often used positivity threshold was 15%. Six publications compared <em>RET</em>-FISH with at least one other molecular technique on at least eight samples, and the concordance was variable, from 5.9% to 66.7% for FISH-positive cases. Regarding our data, out of the 784 analyzed samples, 32 (4%) were positive by <em>RET</em>-FISH. The concordance between <em>RET</em>-FISH and RNA-seq in <em>RET</em>-FISH positive samples was 69%.</div></div><div><h3>Conclusions</h3><div>Overall, both existing literature and our data suggest that <em>RET</em>-FISH testing can be used for rapid screening of <em>RET</em> rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm <em>RET</em>-FISH-positive cases is essential for ensuring that only patients likely to benefit from <em>RET</em>-target therapy receive the treatment.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined RET and MEK Inhibition as a Treatment for RET Fusion-Positive NSCLC With Acquired BRAF Fusion: A Case Report","authors":"","doi":"10.1016/j.jtocrr.2024.100724","DOIUrl":"10.1016/j.jtocrr.2024.100724","url":null,"abstract":"<div><div><em>RET</em> fusions are present in 1% to 2% of NSCLCs. Although RET inhibitors like selpercatinib are effective, resistance inevitably develops. We present the case of a 28-year-old female with recurrent NSCLC and a <em>CCDC6::RET</em> fusion treated with selpercatinib. Testing at the time of progression revealed a new <em>SKAP2</em><em>:</em>:BRAF fusion. She was then treated with a combination of selpercatinib and trametinib, which led to a likely partial response, despite the combination demonstrating side effects. This case report details the first known instance of NSCLC with a <em>RET</em> fusion developing resistance by means of a <em>BRAF</em> fusion, treated with combined RET and MEK inhibition.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Molecular Features of SCLC With a Clinical RNA Expression Panel","authors":"","doi":"10.1016/j.jtocrr.2024.100723","DOIUrl":"10.1016/j.jtocrr.2024.100723","url":null,"abstract":"<div><h3>Introduction</h3><div>The translation of gene expression profiles of SCLC to clinical testing remains relatively unexplored. In this study, gene expression variations in SCLC were evaluated to identify potential biomarkers.</div></div><div><h3>Methods</h3><div>RNA expression profiling was performed on 44 tumor samples from 35 patients diagnosed with SCLC using the clinically validated RNA Salah Targeted Expression Panel (RNA STEP). RNA sequencing (RNA-Seq) and immunohistochemistry were performed on two different SCLC cohorts, and correlation analyses were performed for the <em>ASCL1</em>, <em>NEUROD1</em>, <em>POU2F3</em>, and <em>YAP1</em> genes and their corresponding proteins. RNA STEP and RNA-Seq results were evaluated for gene expression profiles and heterogeneity between SCLC primary and metastatic sites. RNA STEP gene expression profiles of independent SCLC samples (n = 35) were compared with lung adenocarcinoma (n = 160) and squamous cell carcinoma results (n = 25).</div></div><div><h3>Results</h3><div>The RNA STEP results were highly correlated with RNA-Seq and immunohistochemistry results. The dominant transcription regulator by RNA STEP was <em>ASCL1</em> in 74.2% of the samples, <em>NEUROD1</em> in 20%, and <em>POU2F3</em> in 2.9%. The <em>ASCL1</em>, <em>NEUROD1</em>, and <em>POU2F3</em> gene expression profiles were heterogeneous between primary and metastatic sites. SCLCs displayed markedly high expression for targetable genes <em>DLL3</em>, <em>EZH2</em>, <em>TERT</em>, and <em>RET</em>. SCLCs were found to have relatively colder immune profiles than lung adenocarcinomas and squamous cell carcinomas, characterized by lower expression of <em>HLA</em> genes, immune cell, and immune checkpoint genes, except the <em>LAG3</em> gene.</div></div><div><h3>Conclusions</h3><div>Clinical-grade SCLC RNA expression profiling has value for SCLC subtyping, design of clinical trials, and identification of patients for trials and potential targeted therapy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: Impact of Maintenance Pemetrexed Cessation on Clinical Outcomes of Patients With Metastatic Nonsquamous NSCLC","authors":"","doi":"10.1016/j.jtocrr.2024.100717","DOIUrl":"10.1016/j.jtocrr.2024.100717","url":null,"abstract":"<div><h3>Introduction</h3><div>Combination chemoimmunotherapy including pemetrexed and a PD(L)1 inhibitor is a common first-line systemic therapy approach for patients with metastatic nonsquamous NSCLC. Patients often discontinue maintenance pemetrexed due to adverse effects, and little is known about the impact of maintenance pemetrexed cessation on real-world progression-free survival (rwPFS) and overall survival (OS).</div></div><div><h3>Methods</h3><div>A total of 121 patients with stage IV or recurrent, metastatic nonsquamous NSCLC treated at Vanderbilt University Medical Center (VUMC) were included in this retrospective analysis. Patients diagnosed between July 2017 and September 2023 were included if they received maintenance pemetrexed and pembrolizumab. Patients were divided into two groups: those who stopped pemetrexed due to toxicity and those who did not. rwPFS and OS were measured from time of stage IV or metastatic diagnosis to the date of radiographic progression or death, respectively.</div></div><div><h3>Results</h3><div>Among patients with stage IV or recurrent, metastatic NSCLC (n = 121), who remained on maintenance pemetrexed and pembrolizumab (n = 68), the median rwPFS was 11.7 months (95% confidence interval [CI]: 7.47–not applicable [NA]) compared with 24.3 months (95% CI, 19.37–NA) among patients who stopped maintenance pemetrexed (n = 53) (<em>p</em> = 0.1). The median OS in the same patient groups was 25.8 months (95% CI: 13.8–NA) compared with 36.4 months (95% CI: 26.9–NA) (<em>p</em> = 0.15), respectively.</div></div><div><h3>Conclusions</h3><div>In this study of patients with metastatic nonsquamous NSCLC who received maintenance pemetrexed and pembrolizumab, patients who stopped pemetrexed due to toxicity experienced similar outcomes to those who continued with pemetrexed. The optimal duration of maintenance chemotherapy should be further evaluated in the immunotherapy era.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Uptake of the Lung Cancer Core Outcome Set: A Cross-Sectional Analysis","authors":"","doi":"10.1016/j.jtocrr.2024.100713","DOIUrl":"10.1016/j.jtocrr.2024.100713","url":null,"abstract":"<div><h3>Introduction</h3><div>A core outcome set (COS) helps standardize outcome measurements across clinical trials. Although lung cancer is the leading cause of cancer-related deaths, research exploring COS implementation across lung cancer trials remains limited. We aim to analyze the uptake of the lung cancer COS and identify potential gaps in COS adherence.</div></div><div><h3>Methods</h3><div>On June 26, 2023, we conducted a cross-sectional analysis of clinical trials that evaluated lung cancer interventions. Our sample consisted of studies registered on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform between September 2011 and June 2023. In a masked and duplicate fashion, investigators extracted data regarding trial characteristics and COS adoption. An interrupted time series analysis was conducted to evaluate the adherence of lung cancer COS before and after its publication.</div></div><div><h3>Results</h3><div>Of the 626 observed trials, we found no overall significant difference in lung cancer COS uptake pre- and post-publication (0.01%, 95% confidence interval: −0.16% to 0.19%, <em>p</em>=0.85). The most frequently measured outcomes were “overall survival” (91.69%%) and “treatment-related mortalities” (54.69%). Health-related quality of life questionnaires were typically used to evaluate outcomes in the “Degree of health” domain (49.20%). Outcomes related to “time from diagnosis to treatment” (0%), “place of death” (0.16%), and “duration of time spent in the hospital at the end of life” (1.60%) were rarely measured.</div></div><div><h3>Conclusions</h3><div>Despite the advantages of COS implementation, adherence across lung cancer clinical trials remains alarmingly low—which could compromise data reliability and patient care. Our findings showcase these inconsistencies and emphasize the need for proactive approaches to improve uptake.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Final Analysis Data and Exploratory Biomarker Analysis of a Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib Monotherapy for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: The WJOG9717L Study","authors":"","doi":"10.1016/j.jtocrr.2024.100716","DOIUrl":"10.1016/j.jtocrr.2024.100716","url":null,"abstract":"<div><h3>Introduction</h3><div>EGFR tyrosine kinase inhibitors have been the standard treatment for patients with NSCLC who have sensitive <em>EGFR</em> mutations. This study revealed final analysis survival data, biomarkers, and resistance mechanisms of osimertinib plus bevacizumab or osimertinib monotherapy in previously untreated patients with advanced <em>EGFR</em>-positive nonsquamous NSCLC.</div></div><div><h3>Methods</h3><div>We previously reported the primary results of a randomized, open-label, phase 2 study comparing osimertinib plus bevacizumab with osimertinib monotherapy for this population. In this exploratory analysis using tissue and plasma samples, we evaluated gene profiles at baseline and disease progression or the last dose using targeted deep sequencing.</div></div><div><h3>Results</h3><div>The median progression-free survival (PFS) by the blinded independent central reviewer was 22.1 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (hazard ratio [HR] = 0.864, 95% confidence interval [CI]: 0.549–1.359). The 3-year overall survival was not different between the two arms (osimertinib plus bevacizumab: 57.1%; osimertinib monotherapy: 65.0%; HR 1.271, 95% CI: 0.727–2.223). A total of 94 patients had assessable plasma samples at baseline, and 40 had assessable pretreatment tissue samples. <em>EGFR</em> mutations (76.6%) and <em>TP53</em> mutations (44.7%) were detected in plasma samples at baseline. In patients with plasma <em>TP53</em> mutations (n = 42), the median PFS by blinded independent central reviewer was 19.8 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (HR = 1.107, 95% CI: 0.534–2.297).</div></div><div><h3>Conclusions</h3><div>There was also no significant difference in the PFS between the two arms, even in patients with <em>TP53</em> mutations.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Resected Lung Cancer Diagnosed Through Screening and Incidental Pulmonary Nodule Programs in a Mississippi Delta Cohort","authors":"","doi":"10.1016/j.jtocrr.2024.100684","DOIUrl":"10.1016/j.jtocrr.2024.100684","url":null,"abstract":"<div><h3>Introduction</h3><p>Early lung cancer detection programs improve surgical resection rates and survival but may skew toward more indolent cancers.</p></div><div><h3>Methods</h3><p>Hypothesizing that differences in stage-stratified survival indicate differences in biological aggressiveness and possible length-time and overdiagnosis bias, we assessed a cohort who had curative-intent resection, categorized by diagnostic pathways: screening, incidental pulmonary nodule program, and non–program based. Survival was analyzed using Kaplan-Meier plots, log-rank tests, and Cox regression, comparing aggregate and stage-stratified survival across cohorts with Tukey’s method for multiple testing.</p></div><div><h3>Results</h3><p>Of 1588 patients, 111 patients (7%), 357 patients (22.5%), and 1120 patients (70.5%) were diagnosed through screening, pulmonary nodule, and non–program-based pathways; 0% versus 9% versus 6% were older than 80 years (<em>p</em> = 0.0048); 17%, 23%, and 24% had a Charlson Comorbidity score greater than or equal to 2 (<em>p</em> = 0.0143); 7%, 6%, and 9% had lepidic adenocarcinoma; 26%, 31%, and 34% had poorly or undifferentiated tumors (<em>p</em> = 0.1544); and 93%, 87%, and 77% had clinical stage I (<em>p</em> &lt; 0.0001).</p><p>Aggregate 5-year survival was 87%, 72%, and 65% (<em>p</em> = 0.0009), including 95%, 74%, and 74% for pathologic stage I. Adjusted pairwise comparisons showed similar survival in screening and nodule program cohorts (<em>p</em> = 0.9905). Nevertheless, differences were significant between screening and non–program-based cohorts (<em>p</em> = 0.0007, adjusted hazard ratio 0.33 [95% confidence interval: 0.18–0.6]) and between nodule and nonprogram cohorts (adjusted hazard ratio 0.77 [95% confidence interval: 0.61–0.99]). Stage I comparisons yielded <em>p</em> = 0.2256, 0.1131, and 0.911. In respective pathways, 0%, 2%, and 2% of patients with stage I disease who were older than 80 years had a Charlson score greater than or equal to 2 (<em>p</em> = 0.3849).</p></div><div><h3>Conclusions</h3><p>Neither length-time nor overdiagnosis bias was evident in NSCLC diagnosed through screening or incidental pulmonary nodule programs.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000547/pdfft?md5=fe71fffad0f93d3e07e846b753b44c5b&pid=1-s2.0-S2666364324000547-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141032750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Is the Accuracy of Clinical Staging for Stage III-Single-station N2 NSCLC? A Multi-Centre UK Study","authors":"","doi":"10.1016/j.jtocrr.2024.100694","DOIUrl":"10.1016/j.jtocrr.2024.100694","url":null,"abstract":"<div><h3>Introduction</h3><p>Single-station N2 (ssN2) versus multi-station N2 has been used as a selection criterion for treatment recommendations between surgical versus non-surgical multimodality treatment in stage III-N2 NSCLC. We hypothesized that clinical staging would be susceptible to upstaging on pathologic staging and, therefore, challenge this practice.</p></div><div><h3>Methods</h3><p>A retrospective study of prospectively collected routine clinical data for patients with stage III-N2 NSCLC that had completed computed tomography (CT), positron emission tomography (PET), and staging endobronchial ultrasound (EBUS) and had been confirmed clinical stage III-ssN2 at multidisciplinary team discussion and went on to complete surgical resection as the first treatment to provide pathologic staging. The study was completed in two cohorts (A) across a single cancer alliance in England (Greater Manchester) January 1, 2015 to December 31, 2018 and (B) across five United Kingdom centers to validate the findings in part A January 1, 2016 to December 31, 2020.</p></div><div><h3>Results</h3><p>A total of 115 patients met the inclusion criteria across cohort A (56 patients) and cohort B (59 patients) across 15 United Kingdom hospitals. The proportion of cases in which clinical stage III-ssN2 was upstaged to pathologic stage III-multi-station N2 was 34% (19 of 56) in cohort A, 32% in cohort B (19 of 59), and 33% across the combined study cohort (38 of 115). Most patients had a single radiologically abnormal lymph node on CT and PET (88%, 105 of 115). In the majority, the reasons for missed N2 disease on staging EBUS were due to inaccessible (stations 5, 6, 8, 9) N2 nodes at EBUS (34%, 13 of 38) and accessible lymph nodes not sampled during staging EBUS as not meeting sampling threshold (40%, 15 of 38) rather than false-negative sampling during EBUS (26%, 10 of 38).</p></div><div><h3>Conclusions</h3><p>During multidisciplinary team discussions, clinicians must be aware that one-third of patients with stage III-ssN2 on the basis of CT, PET, and staging EBUS do not truly have ssN2 and this questions the use of this criterion to define treatment recommendations.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266636432400064X/pdfft?md5=e1d99c1775c09c768cbd9f7b6d17a11b&pid=1-s2.0-S266636432400064X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141954595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Long-Term Survivors With EGFR-Mutant Metastatic NSCLC","authors":"","doi":"10.1016/j.jtocrr.2024.100669","DOIUrl":"10.1016/j.jtocrr.2024.100669","url":null,"abstract":"<div><h3>Introduction</h3><p>Characteristics of long-term survivors in EGFR-mutant (EGFRm) NSCLC are not fully understood. This retrospective analysis evaluated a multi-institution cohort of patients with EGFRm NSCLC treated in the pre-osimertinib era and sought to describe characteristics of long-term survivors.</p></div><div><h3>Methods</h3><p>Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with EGFRm metastatic NSCLC who started first-line therapy before 2015. Demographics and comutations were compared between greater than or equal to 5-year survivors and less than 5-year survivors. Multivariable Cox proportional hazard and logistic regression models were used to evaluate factors associated with survival and the odds of death within 5 years, respectively.</p></div><div><h3>Results</h3><p>Overall, 133 patients were greater than or equal to 5-year survivors; 127 were less than 5-year survivors. Burden of pathogenic comutations including TP53 and PIK3CA was similar between greater than or equal to 5-year survivors and less than 5-year survivors. Receipt of first-line chemotherapy rather than EGFR tyrosine kinase inhibitor was similar between the groups (22% of &lt;5-y versus 31% of ≥5-y). Baseline brain metastasis and history of smoking were associated with higher odds of death within 5 years (odds ratio = 2.16, <em>p</em> = 0.029 and odds ratio = 1.90, <em>p</em> = 0.046, respectively). Among patients without baseline brain metastases, cumulative incidence of brain metastases at 5 years was 42.3%. Both baseline and post-baseline brain metastasis were associated with worse overall survival compared with no brain metastasis (hazard ratio = 3.26, <em>p</em> &lt; 0.001 and hazard ratio = 4.99, <em>p</em> &lt; 0.001, respectively).</p></div><div><h3>Conclusions</h3><p>Within patients treated for EGFRm metastatic NSCLC before 2015, absence of brain metastasis and nonsmoking status were predictive of 5-year survival. Our findings help to define a subset of patients with EGFRm NSCLC with excellent survival outcomes who may not require intensification of initial therapy.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000390/pdfft?md5=7beef34d332e2623a0877e47948d1c1b&pid=1-s2.0-S2666364324000390-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140400551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}