Journal of Thoracic Oncology最新文献

{"title":"The Phase 3 KEYLYNK-006 Study of Pembrolizumab plus Olaparib versus Pembrolizumab plus Pemetrexed as Maintenance Therapy for Metastatic Nonsquamous Non-Small-Cell Lung Cancer.","authors":"Jhanelle E Gray, Michael Schenker, Mehmet Ali Nahit Şendur, Viktoriya Leonova, Dariusz Kowalski, Terufumi Kato, Rashida Orlova, James Chih-Hsin Yang, Adrian Langleben, Arnold Pilz, Andrei Ungureanu, Milena Perez Mak, Flavia De Angelis, Himani Aggarwal, Zachary Zimmer, Bin Zhao, Mark Shamoun, Tae Min Kim","doi":"10.1016/j.jtho.2024.10.026","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.10.026","url":null,"abstract":"<p><strong>Background: </strong>Poly (ADP-ribose) inhibitors, including olaparib, upregulate programmed cell death ligand 1 (PD-L1), which may increase efficacy of anti-PD-(L)1 therapies.</p><p><strong>Methods: </strong>In the phase 3 KEYLYNK-006 trial (NCT03976323), eligible adults with previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations who had complete response (CR), partial response (PR), or stable disease (SD) following induction therapy with 4 cycles of pembrolizumab 200 mg Q3W, pemetrexed 500 mg/m² , and carboplatin AUC5 or cisplatin 75 mg/m² were randomized 1:1 to olaparib 300 mg orally twice daily or pemetrexed Q3W, both given with ≤31 cycles of pembrolizumab Q3W. Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (IA2; ie, final PFS analysis), OS at final analysis (FA).</p><p><strong>Results: </strong>Of 1003 patients who received induction therapy, 672 (67.0%) were randomized to pembrolizumab plus olaparib (n=337) or pembrolizumab plus pemetrexed (n=335) in the intention-to-treat population. Median follow-up at FA was 39.9 (range, 28.1-51.5) months. At IA2, median (95% CI) PFS was 7.1 (5.6-8.7) months versus 8.3 (6.9-11.5) months in the olaparib versus pemetrexed groups (HR, 1.12; 95% CI, 0.92-1.36; P=0.87). At FA, median (95% CI) OS was 20.7 (18.0-24.8) months versus 23.0 (19.0-26.4) months (HR, 1.04; 95% CI, 0.87-1.25; P=0.6649). Grade 3-5 maintenance treatment-related AEs occurred in 26.1% versus 30.1% patients.</p><p><strong>Conclusion: </strong>Pembrolizumab plus maintenance olaparib did not improve PFS or OS versus pembrolizumab plus pemetrexed in previously untreated metastatic nonsquamous NSCLC without targetable genetic alterations.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer. S1929.","authors":"Nagla Abdel Karim, Jieling Miao, Karen L Reckamp, Carl M Gay, Lauren A Byers, Ying-Qi Zhao, Mary W Redman, Daniel R Carrizosa, Wei-Lien Wang, William J Petty, Kathan Mehta, Bryan A Faller, Edem S Agamah, Samer S Kasbari, Rajini K Malisetti, Atul Kumar, John Schallenkamp, Krishna C Alluri, Jhanelle E Gray, Karen Kelly","doi":"10.1016/j.jtho.2024.10.021","DOIUrl":"https://doi.org/10.1016/j.jtho.2024.10.021","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate whether the addition of a poly (ADP-ribose) polymerase inhibitor (PARPi) talazoparib to maintenance immune checkpoint inhibitor (ICI) atezolizumab following frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive stage small cell lung cancer (ES-SCLC).</p><p><strong>Methods: </strong>Patients with newly diagnosed SLFN11 expressing (H-score ≥ 1, evaluated centrally) ES-SCLC were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) following frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a 1-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate (ORR), overall survival (OS), and toxicity. Target sample size was 84 eligible patients.</p><p><strong>Results: </strong>From June 15, 2020 to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A). PFS was improved with AT versus A (hazard ratio [HR], 0.66; 80% confidence interval [CI]: 0.50-0.86; 1-sided P = 0.019) with a median PFS of 2.9 and 2.4 months; OS was not different between groups (HR, 0.98; 80% CI: 0.71-1.36; 1-sided P = 0.47). Grade ≥ 3 non-hematologic treatment-related adverse events (TRAEs) occurred in 17% of patients with AT and 14% of patients with A. Grade ≥ 3 hematological TRAEs were more common in AT (50%) than in A (4%) (P < 0.001).</p><p><strong>Conclusion: </strong>Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “Impact of EML4-ALK Variants and Co-Occurring TP53 Mutations on Duration of First-Line ALK Tyrosine Kinase Inhibitor Treatment and Overall Survival in ALK Fusion-Positive NSCLC: Real-World Outcomes From the GuardantINFORM Database”","authors":"Jia Zhang MD,&nbsp;Guoying Wang MD,&nbsp;Xiaoming Zhou MD","doi":"10.1016/j.jtho.2024.07.023","DOIUrl":"10.1016/j.jtho.2024.07.023","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages e63-e64"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Game is Afoot – Seeking Early-Stage Lung Cancer Circulating Tumor DNA","authors":"Marie-Frédérique D’Amours MD, FRCPC ,&nbsp;Curtis B. Hughesman PhD, PEng ,&nbsp;Stephen T. Yip MD, FRCPC ,&nbsp;Cheryl Ho MD, FRCPC","doi":"10.1016/j.jtho.2024.08.014","DOIUrl":"10.1016/j.jtho.2024.08.014","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1479-1481"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Utility of Tumor-Naïve Presurgical Circulating Tumor DNA Detection in Early-Stage NSCLC","authors":"","doi":"10.1016/j.jtho.2024.07.002","DOIUrl":"10.1016/j.jtho.2024.07.002","url":null,"abstract":"<div><h3>Objectives</h3><div>The use of tumor-informed circulating tumor DNA (ctDNA) testing in patients with early-stage disease before surgery is limited, mainly owing to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected NSCLC.</div></div><div><h3>Method</h3><div>We analyzed presurgical plasma samples from 895 patients with <em>EGFR</em> and anaplastic lymphoma kinase-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histologic diagnosis, histologic subtypes, and clinical-to-pathologic TNM upstaging.</div></div><div><h3>Results</h3><div>Presurgical ctDNA detection was observed in 55 of 414 patients (13%) with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (2-year recurrence-free survival 69% versus 91%; log-rank <em>p</em> &lt; 0.001), approaching that of clinical stage II LUAD. Presurgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict presurgical ctDNA detection. Moreover, presurgical ctDNA detection was predictive of the postsurgical discovery of International Association for the Study of Lung Cancer grade 3 tumors (<em>p</em> &lt; 0.001) and pathologic TNM upstaging (<em>p</em> &lt; 0.001). Notably, presurgical ctDNA detection strongly correlated with higher programmed death-ligand 1 expression in tumors (positive rates 28% versus 55%, <em>p</em> &lt; 0.001), identifying a subgroup likely to benefit from anti–programmed death-ligand 1 therapies.</div></div><div><h3>Conclusion</h3><div>These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need for tumor tissue profiling. Furthermore, it is clinically useful in identifying patients at high risk who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1512-1524"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking Progression of EGFR Mutation Positive NSCLC From Blood: Is This the Prime Time?","authors":"Si-Yang Maggie Liu MD, PhD ,&nbsp;Molly Siu Ching Li M.B.B.S.","doi":"10.1016/j.jtho.2024.08.032","DOIUrl":"10.1016/j.jtho.2024.08.032","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1482-1485"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EML4-ALK Variants and Co-Occurring TP53 Mutations in a Real-World Treatment Setting: Do They Matter?","authors":"Alessandra Bearz MD ,&nbsp;Monica Schiappacassi PhD","doi":"10.1016/j.jtho.2024.09.1378","DOIUrl":"10.1016/j.jtho.2024.09.1378","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1489-1491"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equipoise Remains a Major Consideration in the Ethical Evaluation of Phase 3 Randomized Controlled Trials Involving Precision Oncology Approaches in NSCLC","authors":"Sarah Heynemann M.B.B.S., BMedSci, FRACP, MBioeth ,&nbsp;Wendy Lipworth M.B.B.S., PhD ,&nbsp;Sue-Anne McLachlan M.B.B.S., MSc, FRACP ,&nbsp;Jennifer Philip M.B.B.S., GDipPallMed, MMed, PhD ,&nbsp;Tom John M.B.B.S., PhD, FRACP ,&nbsp;Ian Kerridge BA, BMed(Hons), MPhil(Cantab), FRACP, FRCPA","doi":"10.1016/j.jtho.2024.07.004","DOIUrl":"10.1016/j.jtho.2024.07.004","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1504-1508"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of EML4-ALK Variants and Co-Occurring TP53 Mutations on Duration of First-Line ALK Tyrosine Kinase Inhibitor Treatment and Overall Survival in ALK Fusion-Positive NSCLC: Real-World Outcomes From the GuardantINFORM database","authors":"Kaushal Parikh MD ,&nbsp;Anastasios Dimou MD ,&nbsp;Konstantinos Leventakos MD, PhD ,&nbsp;Aaron S. Mansfield MD ,&nbsp;Mohamed Shanshal MD ,&nbsp;Yin Wan MS ,&nbsp;Huamao M. Lin PhD ,&nbsp;Sylvie Vincent PhD ,&nbsp;Jennifer Elliott PhD ,&nbsp;Ioana R. Bonta MD","doi":"10.1016/j.jtho.2024.07.009","DOIUrl":"10.1016/j.jtho.2024.07.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Tyrosine kinase inhibitors (TKIs) are first-line treatment options for <em>ALK</em>-positive (<em>ALK</em>+) NSCLC. Factors such as variant allele frequencies (VAFs), <em>EML4-ALK</em> fusion variant, and concurrent <em>TP53</em> mutations (<em>TP53</em>mt) in circulating tumor DNA (ctDNA) may affect treatment outcomes. We evaluated their effects on time to discontinuation (TTD) of first-line treatment with next-generation ALK TKIs in a real-world setting.</div></div><div><h3>Methods</h3><div>Adults with advanced or metastatic NSCLC and ctDNA-detected <em>ALK</em> fusion who received first-line next-generation ALK TKI monotherapy were identified in GuardantINFORM. Effects of <em>ALK</em> fusion VAF, <em>EML4-ALK</em> variants, and <em>TP53</em>mt detection on TTD were evaluated.</div></div><div><h3>Results</h3><div>A total of 307 patients with <em>ALK</em> fusion in baseline ctDNA received first-line alectinib (n = 280), brigatinib (n = 15), lorlatinib (n = 9), or ceritinib (n = 3); 150 patients (49%) had <em>ALK-</em>fusion VAF greater than or equal to 1%. Among 232 patients with <em>EML4-ALK</em> fusions (v1, 50%; v3, 36%), <em>TP53</em>mt co-occurred with v1 in 42 (18%) and v3 in 32 (14%). Patients with VAF less than 1% versus greater than or equal to 1% had a median TTD of 32.2 (95% confidence interval [CI]: 20.7–not estimable [NE]) versus 14.7 months (10.4–19.9; hazard ratio [HR] = 1.57 [95% CI: 1.09–2.26]; <em>p =</em> 0.0146). Median TTD was 13.1 (9.5–19.9) versus 27.6 months (17.3–NE) in patients with versus without <em>TP53</em>mt detected (HR = 1.53 [1.07–2.19]; <em>p =</em> 0.0202) and 20.3 (14.4–NE) versus 11.5 months (7.4–31.1) in patients with v1 versus v3 (HR = 1.29 [0.83–2.01]; <em>p =</em> 0.2641). Patients with <em>TP53</em>mt and v3 had a median TTD of 7.4 months (95% CI: 4.2–31.1).</div></div><div><h3>Conclusion</h3><div>High ctDNA VAF, <em>EML4-ALK</em> v3, and <em>TP53</em>mt were associated with early discontinuation of first-line ALK TKIs.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Pages 1539-1549"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meeting Announcements","authors":"","doi":"10.1016/S1556-0864(24)02366-9","DOIUrl":"10.1016/S1556-0864(24)02366-9","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"19 11","pages":"Page A4"},"PeriodicalIF":21.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}