JTO Clinical and Research Reports最新文献

{"title":"Racial Differences in Systemic Immune Parameters in Individuals With Lung Cancer","authors":"Mitchell S. von Itzstein MD ,&nbsp;Jialiang Liu PhD ,&nbsp;Hong Mu-Mosley PhD ,&nbsp;Farjana Fattah PhD ,&nbsp;Jason Y. Park MD, PhD ,&nbsp;Jeffrey A. SoRelle MD ,&nbsp;J. David Farrar PhD ,&nbsp;Mary E. Gwin MD ,&nbsp;David Hsiehchen MD ,&nbsp;Yvonne Gloria-McCutchen ,&nbsp;Edward K. Wakeland PhD ,&nbsp;Suzanne Cole MD ,&nbsp;Sheena Bhalla MD ,&nbsp;Radhika Kainthla MD ,&nbsp;Igor Puzanov MD, MSCI ,&nbsp;Benjamin Switzer DO, MHSA, MS ,&nbsp;Gregory A. Daniels MD, PhD ,&nbsp;Yousef Zakharia MD ,&nbsp;Montaser Shaheen MD ,&nbsp;Jianjun Zhang MD, PhD ,&nbsp;David E. Gerber MD","doi":"10.1016/j.jtocrr.2024.100751","DOIUrl":"10.1016/j.jtocrr.2024.100751","url":null,"abstract":"<div><h3>Introduction</h3><div>Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer.</div></div><div><h3>Methods</h3><div>Patients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. Clinical and demographic information were obtained from electronic medical records. Pretreatment peripheral blood samples were collected and analyzed for cytokines using a multiplex panel and for immune cell populations using mass cytometry. Differences between Black and White patients were determined and corrected for multiple comparisons.</div></div><div><h3>Results</h3><div>A total of 187 patients with NSCLC (Black, 19; White, 168) were included in the analysis. Compared with White patients, Black patients had greater comorbidity (median Charlson Comorbidity Index 5 versus 3; <em>p</em> = 0.04) and were more likely to have received previous chemotherapy (79% versus 47%; <em>p</em> = 0.03). Black patients had significantly lower levels of CCL23 and CCL27 and significantly higher levels of CCL8, CXCL1, CCL26, CCL25, CCL1, IL-1b, CXCL16, and IFN-γ (all <em>p</em> &lt; 0.05, false discovery rate &lt; 0.1). Black patients also exhibited greater populations of nonclassical CD16+ monocytes, NKT-like cells, CD4+ cells, CD38+ monocytes, and CD57+ gamma delta T cells (all <em>p</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>Black and White patients with lung cancer exhibit several differences in immune parameters, with Black patients exhibiting greater levels of numerous proinflammatory cytokines and cell populations. The etiology and clinical significance of these differences warrant further evaluation.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100751"},"PeriodicalIF":3.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142656219","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":"First Report of Response to Tarlatamab in a Patient With DLL3-Positive Pulmonary Carcinoid: Case Report","authors":"Alissa J. Cooper MD ,&nbsp;Natasha Rekhtman MD, PhD ,&nbsp;Marina K. Baine MD, PhD ,&nbsp;Marie C. Thomas DNP, FNP-C ,&nbsp;Alia C. Lynch PharmD, BCOP ,&nbsp;Ryan D. Gentzler MD, MS","doi":"10.1016/j.jtocrr.2024.100750","DOIUrl":"10.1016/j.jtocrr.2024.100750","url":null,"abstract":"<div><div>Tarlatamab, a DLL3-targeting bispecific T-cell engager, has rapidly assumed the role of a new standard of care in the later-line treatment of extensive-stage SCLC. Little is known about the efficacy of tarlatamab in other histologies such as DLL3-expressing metastatic pulmonary carcinoid tumor, a clinical entity without many approved management options. Here, we report the case of a patient with metastatic atypical carcinoid tumor which had progressed on multiple previous therapies. Her tumor strongly expressed DLL3 protein and had clinical response to tarlatamab therapy. This case indicates that this novel therapy may be an efficacious option in other pulmonary neuroendocrine cancers.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100750"},"PeriodicalIF":3.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653674","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":"A Response to the Letter to the Editor: “Heart and Lung Dose as Predictors of Overall Survival in Patients With Locally Advanced Lung Cancer: A National Multicenter Study”","authors":"Agon Olloni MD, PhD,&nbsp;Carsten Brink PhD,&nbsp;Ebbe L. Lorenzen PhD,&nbsp;Stefan S. Jeppesen MD, PhD,&nbsp;Tine Schytte MD, PhD","doi":"10.1016/j.jtocrr.2024.100749","DOIUrl":"10.1016/j.jtocrr.2024.100749","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100749"},"PeriodicalIF":3.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653851","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 of a New Anatomical Region at Risk in Thoracic Radiotherapy: From Discovery to Implementation","authors":"Kathryn Banfill PhD, FRCR ,&nbsp;Thomas Marchant PhD ,&nbsp;Alan McWilliam PhD ,&nbsp;Joseph Wood PhD ,&nbsp;Matthias Schmitt MD, PhD ,&nbsp;Azadeh Abravan PhD ,&nbsp;Gareth Price PhD ,&nbsp;Marcel van Herk PhD ,&nbsp;Corinne Faivre-Finn PhD, FRCR","doi":"10.1016/j.jtocrr.2024.100742","DOIUrl":"10.1016/j.jtocrr.2024.100742","url":null,"abstract":"<div><div>Increasing radiotherapy dose to select cardiac structures is associated with cardiac events and premature death. Previous studies have found a dose–response relationship for structures at the base of the heart.</div><div>We have defined a new cardiac anatomical region at risk for radiotherapy by consensus opinion, based on image-based data-mining studies. The cardiac avoidance area comprises the superior vena cava, right atrium, aortic root, left main coronary artery, and proximal segments of the left anterior descending and right coronary arteries. We describe a contouring atlas for the cardiac avoidance area to facilitate implementation.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100742"},"PeriodicalIF":3.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653848","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":"Phase II Trial of Regorafenib and Oral Methotrexate in Previously Treated Advanced KRAS-Mutant NSCLC","authors":"Jacqueline V. Aredo MD, MS ,&nbsp;Heather A. Wakelee MD ,&nbsp;Kavitha J. Ramchandran MD ,&nbsp;Joel W. Neal MD, PhD ,&nbsp;Maximilian Diehn MD, PhD ,&nbsp;Angela Bik-Yu Hui PhD ,&nbsp;Ameen Salahudeen MD, PhD ,&nbsp;Bernice Kwong MD ,&nbsp;Gerald J. Berry MD ,&nbsp;H. Henry Guo MD, PhD ,&nbsp;Kristen Cunanan PhD ,&nbsp;Shireen Vali PhD ,&nbsp;Danny Pancirer BA ,&nbsp;Vivian Tsang MSN ,&nbsp;Grace Hwang MS ,&nbsp;Monica Loza BA ,&nbsp;Brittany Johnson BA ,&nbsp;Isabelle Blanchard BS ,&nbsp;Sukhmani K. Padda MD","doi":"10.1016/j.jtocrr.2024.100741","DOIUrl":"10.1016/j.jtocrr.2024.100741","url":null,"abstract":"<div><h3>Introduction</h3><div>There are no standard targeted treatment options for advanced <em>KRAS</em>-mutant NSCLC beyond <em>KRAS</em> G12C inhibitors. A computational model identified regorafenib and low-dose methotrexate as synergistic in preclinical models of <em>KRAS</em>-mutant NSCLC. This study evaluated the efficacy and safety of the combination in previously treated advanced <em>KRAS</em>-mutant NSCLC.</div></div><div><h3>Methods</h3><div>This single-arm phase II study included regorafenib 80 to 120 mg oral daily and oral methotrexate dose escalated to tolerability from 10 to 20 mg twice weekly during the first cycle. Both agents were administered on weeks 1 to 3 of each 4-week cycle. The primary end point was progression-free survival.</div></div><div><h3>Results</h3><div>In total, 18 patients with <em>KRAS</em>-mutant NSCLC were enrolled. Five patients received regorafenib at a 120 mg starting dose with four discontinuing due to toxicity; subsequently, 13 patients were treated at an 80 mg starting dose, with eight dose-escalating to 120 mg after the first cycle. Median progression-free survival was 3.7 months (95% confidence interval 1.8–8.6) and median overall survival was 10.4 months (95% confidence interval 5.2–30.3). The objective response rate was 16.7% and the 8-week disease control rate was 66.7%. Grade 3 treatment-related adverse events occurred in 11 patients, most often oral mucositis (n = 2) and asymptomatic lipase increase (n = 2). One patient developed asymptomatic grade 4 lipase increase.</div></div><div><h3>Conclusions</h3><div>Combination treatment of regorafenib and oral methotrexate in patients with <em>KRAS</em>-mutant NSCLC was limited due to toxicity, and the study did not meet its primary end point. Computational modeling may aid in repurposing therapeutic options though caution must be exercised with tolerability.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100741"},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653721","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":"Entrectinib-Induced Myocarditis and Acute Heart Failure Responding to Steroid Treatment: A Case Report","authors":"Mehraab N. Majeed MBBCh ,&nbsp;Subramanian Venkatesan PhD ,&nbsp;Dionysis Papadatos-Pastos PhD ,&nbsp;Tanya Ahmad MD ,&nbsp;Martin Forster PhD ,&nbsp;Polyvios Demetriades MRCP ,&nbsp;Daniel Johnathan Hughes MRCP ,&nbsp;Sarah Benafif PhD ,&nbsp;Siow Ming Lee FRCP","doi":"10.1016/j.jtocrr.2024.100746","DOIUrl":"10.1016/j.jtocrr.2024.100746","url":null,"abstract":"<div><div>A 72-year-old man presented to his general practitioner with worsening dyspnea and was diagnosed with having recurrent <em>ROS1</em>-positive stage IIIB NSCLC 8 years after initial diagnosis and radical treatment for early stage disease. He was subsequently started on entrectinib but required hospital admissions for recurrent acute kidney injuries on a background of chronic kidney disease. His entrectinib was withheld on day 20 since his first dose of treatment while he was being investigated. Nevertheless, he continued to experience worsening dyspnea and bilateral pedal edema and later developed acute pulmonary edema 31 days after his first dose of entrectinib, despite the drug being withheld for the past 11 days. Results of biochemical tests and cardiac imaging confirmed acute myocarditis. Initially, he was treated with standard heart failure medications without clinical improvement or decline in N-terminal pro B-type natriuretic peptide levels. Nevertheless, he noticed significant improvement after starting a short course of prednisolone, which led to complete resolution of symptoms, improved N-terminal pro B-type natriuretic peptide levels, and recovery of left ventricular ejection fraction. His treatment was subsequently changed to crizotinib, which was well tolerated. This is the third reported case of entrectinib-induced myocarditis and the first reported case which has been successfully managed with steroid therapy. This case was also associated with concurrent acute heart failure after entrectinib treatment which responded promptly to prednisolone (40 mg). Entrectinib-induced cardiotoxicity is an important adverse event to be aware of, particularly as patients may be asymptomatic for an initial period before significant deterioration.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100746"},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653673","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":"Multisite Randomized Controlled Trial of CareSTEPS: A Supportive Care Intervention for the Family Caregivers of Patients With Advanced Lung Cancer","authors":"Maria L. Rangel DrPH ,&nbsp;Kathrin Milbury PhD ,&nbsp;Karen Kayser PhD ,&nbsp;Robert Taylor Ripley MD ,&nbsp;Elizabeth Kvale MD ,&nbsp;Hoda Badr PhD","doi":"10.1016/j.jtocrr.2024.100736","DOIUrl":"10.1016/j.jtocrr.2024.100736","url":null,"abstract":"<div><h3>Objectives</h3><div>Patients with advanced lung cancer (LC) face significant physical, psychological, and functional challenges, increasing their reliance on caregivers for practical and emotional support. This study evaluates the efficacy of CareSTEPS (Self-<u>Care</u>, <u>S</u>tress management, Symp<u>t</u>om management, <u>E</u>ffective communication, Problem-solving, and Social support), a 6-week telephone-delivered intervention designed to improve psychological functioning (depression and anxiety symptoms) and reduce caregiver burden among family caregivers of patients with advanced LC.</div></div><div><h3>Methods</h3><div>In this multisite, open-label, parallel-group randomized controlled trial, 174 caregivers (74.1% female individuals, 40.2% from a racial or ethnic minority group) of patients with stage IIIB or IV NSCLC or extensive-stage SCLC completed baseline surveys and were randomly assigned to CareSTEPS (n = 87) or usual care (n = 87) using stratified block randomization. Caregivers in the CareSTEPS arm received a manual with information on self-care, stress management, symptom management, effective communication, problem-solving, and social support. They also participated in six weekly telephone sessions with Masters-level trained interventionists with a mental health background, who provided psychoeducation, skills training, and support. Eight weeks after baseline, caregivers completed a follow-up survey.</div></div><div><h3>Results</h3><div>Using an intent-to-treat framework, analyses of covariance were conducted to assess the efficacy of CareSTEPS, with <em>p</em> values lower than 0.05 indicating significant differences. Caregivers who received CareSTEPS reported improved psychological functioning and lower burden compared with those who received usual care, with effect sizes ranging from small to large (depression d = −0.55, anxiety d = −0.81, burden d = −0.37).</div></div><div><h3>Conclusions</h3><div>The CareSTEPS intervention reports great promise in meeting the critical support needs of the family caregivers of patients with advanced LC, significantly improving caregivers' psychological functioning and reducing their burden. Overall, the findings emphasize the importance of incorporating caregiver support into the comprehensive management of advanced LC.</div></div><div><h3>Clinical Trial Registration</h3><div>ClinicalTrials.gov <span><span>NCT02414672</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100736"},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653677","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":"Prognostic and Predictive Biomarkers of Oligometastatic NSCLC: New Insights and Clinical Applications","authors":"Mandy Jongbloed MD ,&nbsp;Martina Bortolot MD ,&nbsp;Leonard Wee PhD ,&nbsp;Jarno W.J. Huijs MD ,&nbsp;Murillo Bellezo PhD ,&nbsp;Rianne D.W. Vaes PhD ,&nbsp;Frank Aboubakar Nana MD, PhD ,&nbsp;Koen J. Hartemink MD, PhD ,&nbsp;Dirk K.M. De Ruysscher MD, PhD ,&nbsp;Lizza E.L. Hendriks MD, PhD","doi":"10.1016/j.jtocrr.2024.100740","DOIUrl":"10.1016/j.jtocrr.2024.100740","url":null,"abstract":"<div><div>This review discusses the current data on predictive and prognostic biomarkers in oligometastatic NSCLC and discusses whether biomarkers identified in other stages and widespread metastatic disease can be extrapolated to the oligometastatic disease (OMD) setting. Research is underway to explore the prognostic and predictive value of biological attributes of tumor tissue, circulating cells, the tumor microenvironment, and imaging findings as biomarkers of oligometastatic NSCLC. Biomarkers that help define true OMD and predict outcomes are needed for patient selection for oligometastatic treatment, and to avoid futile treatments in patients that will not benefit from locoregional treatment. Nevertheless, these biomarkers are still in the early stages of development and lack prospective validation in clinical trials. Furthermore, the absence of a clear definition of OMD contributes to a heterogeneous study population in which different types of OMD are mixed and treatment strategies are different. Multiple tissue-based, circulating, and imaging features are promising regarding their prognostic and predictive role in NSCLC, but data is still limited and might be biased owing to the inclusion of heterogeneous patient populations. Larger homogeneous and prospective series are needed to assess the prognostic and predictive role of these biomarkers. As obtaining tissue can be difficult and is invasive, the most promising tools for further evaluation are liquid biopsies and imaging-based biomarkers as these can also be used for longitudinal follow-up.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100740"},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653676","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":"Prognostic Value of KRAS/TP53 Status for Overall Survival in First-Line Monoimmunotherapy and Chemoimmunotherapy Treated Patients With Nonsquamous NSCLC in the Netherlands: A Brief Report","authors":"Vincent D. de Jager MD ,&nbsp;Léon C. van Kempen PhD ,&nbsp;Betzabel N. Cajiao Garcia MSc ,&nbsp;T. Jeroen N. Hiltermann MD, PhD ,&nbsp;Anthonie J. van der Wekken MD, PhD ,&nbsp;Ed Schuuring PhD ,&nbsp;Stefan M. Willems MD, PhD","doi":"10.1016/j.jtocrr.2024.100745","DOIUrl":"10.1016/j.jtocrr.2024.100745","url":null,"abstract":"<div><h3>Introduction</h3><div>Programmed death-ligand 1 (PD-L1) is the main predictive biomarker used to identify patients with NSCLC who are eligible for treatment with immune checkpoint inhibitors. Despite its utility, the predictive capacity of PD-L1 is limited, necessitating the exploration of supplementary predictive biomarkers. In this report, we describe the prognostic value of <em>KRAS</em>/<em>TP53</em> mutation status for overall survival (OS) in patients with NSCLC treated with first-line immunotherapy or combined chemoimmunotherapy.</div></div><div><h3>Methods</h3><div>Clinical data of all patients diagnosed with metastatic nonsquamous NSCLC in the Netherlands between January 1 and December 31 of 2019 were retrieved from the Netherlands Cancer Registry and linked to pathology reports of the Dutch Nationwide Pathology Databank. A total of 694 patients with available <em>KRAS</em> and <em>TP53</em> mutation status and treated with first-line pembrolizumab or chemoimmunotherapy were included, with a median follow-up time of 42.5 months. Patients with an <em>EGFR</em> or <em>MET</em> mutation or <em>ALK</em>, <em>ROS1,</em> or <em>RET</em> fusion were excluded from the analysis.</div></div><div><h3>Results</h3><div>Among patients treated with first-line pembrolizumab or chemoimmunotherapy, mutations in <em>KRAS</em> and <em>TP53</em> occurred in 48.8% (n = 339) and 58.4% (n = 405), respectively. OS differed significantly between <em>KRAS</em>/<em>TP53</em> mutational subgroups in patients treated with first-line pembrolizumab or chemoimmunotherapy (log-rank test, <em>p</em> = 0.007). Median OS of pembrolizumab or chemoimmunotherapy treated patients with mutated <em>TP53</em> was longer in patients with <em>KRAS</em>-wildtype (485 versus 359 d, hazard ratio [HR] = 0.76, <em>p</em> = 0.028) or mutated <em>KRAS</em> (571 versus 447 d, HR = 0.73, <em>p</em> = 0.019). In a separate analysis of treatment subgroups, mutated <em>TP53</em> was associated with longer median OS in chemoimmunotherapy treated <em>KRAS</em>-wildtype patients (468 versus 341 d, HR = 0.71, <em>p</em> = 0.029) but not in monoimmunotherapy treated patients with <em>KRAS</em>-wildtype (512 versus 371 d, HR = 0.91, <em>p</em> = 0.78). In multivariable Cox regression analysis including age, sex, clinical disease stage, and PD-L1 tumor proportion score, <em>KRAS</em>/<em>TP53</em> mutation status was no longer associated with OS.</div></div><div><h3>Conclusions</h3><div>Among patients with metastatic NSCLC who are treated with pembrolizumab or chemoimmunotherapy, the presence of a pathogenic <em>TP53</em> and <em>KRAS</em> mutation is associated with longer OS. Nevertheless, in multivariable Cox regression analysis including age, sex, clinical disease stage, and PD-L1 tumor proportion score, <em>KRAS</em>/<em>TP53</em> mutation status was no longer associated with OS.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100745"},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653720","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":"Clinical Outcomes of Maintenance Durvalumab After Definitive Concurrent Chemoradiotherapy in Unresectable Locally Advanced Stage III NSCLC According to EGFR and ALK Status: Korean Cancer Study Group LU-22-18","authors":"Dae-Ho Choi MD ,&nbsp;Miso Kim MD, PhD ,&nbsp;Young Saing Kim MD, PhD ,&nbsp;Keon Uk Park MD, PhD ,&nbsp;Jang Ho Cho MD, PhD ,&nbsp;Hongsik Kim MD, PhD ,&nbsp;Ki Hyeong Lee MD, PhD ,&nbsp;Heejoon Ahn MD, PhD ,&nbsp;Il-Hwan Kim MD, PhD ,&nbsp;Kyung-Hee Lee MD, PhD ,&nbsp;Gyeong-Won Lee MD, PhD ,&nbsp;Seong Yoon Yi MD, PhD ,&nbsp;Beung chul Ahn MD, PhD ,&nbsp;Min-Young Lee MD, PhD ,&nbsp;Hyun Ae Jung MD, PhD ,&nbsp;Sehhoon Park MD, PhD ,&nbsp;Jong-Mu Sun MD, PhD ,&nbsp;Jin Seok Ahn MD, PhD ,&nbsp;Se-Hoon Lee MD, PhD ,&nbsp;Myung-Ju Ahn MD, PhD","doi":"10.1016/j.jtocrr.2024.100734","DOIUrl":"10.1016/j.jtocrr.2024.100734","url":null,"abstract":"<div><h3>Introduction</h3><div>The role of maintenance durvalumab after definitive concurrent chemoradiotherapy (CCRT) in unresectable locally advanced NSCLC with <em>EGFR</em> mutation or <em>ALK</em> translocation remains unclear. We compared the effectiveness of durvalumab maintenance therapy in groups with <em>EGFR</em> and <em>ALK</em> wild-type versus those with <em>EGFR</em> or <em>ALK</em> mutations.</div></div><div><h3>Methods</h3><div>In this retrospective multicenter observational study, patients with locally advanced NSCLC without progression after CCRT followed by maintenance durvalumab and available molecular test results (<em>EGFR</em> and <em>ALK</em>) were eligible. The primary objective was to compare progression-free survival (PFS) between <em>EGFR</em> and <em>ALK</em> wild-type and <em>EGFR</em> or <em>ALK</em> mutant NSCLC. Secondary objectives include overall survival according to <em>EGFR</em> or <em>ALK</em> mutation and programmed death-ligand 1 (PD-L1) expression.</div></div><div><h3>Results</h3><div>Among 339 patients, 279 had wild-type <em>EGFR/ALK</em>, 41 had <em>EGFR</em> mutations and 19 had <em>ALK</em> translocations. The median age was 68 years with 276 male individuals (81.4%) and 63 female individuals (18.6%), 165 (49.3%) had adenocarcinoma, 149 (44.5%) had squamous cell carcinoma, and 21 (6.3%) had other histologic types, 120 (35.4%) had stage IIIA, 168 (49.6%) stage IIIB, and 51 (15.0%) had stage IIIC. Most of the patients (n = 288, 85%) achieved partial response to CCRT, two (0.6%) had a complete response, and 49 patients (14.4%) had stable disease. Excluding four patients with unknown PD-L1 tumor proportion score (TPS), 16 (4.8%) had a PD-L1 TPS of 0, 168 (50.1%) had 1 to 49, and 151 (45.1%) had 50 or higher. The median PFS was 21.4 months (95% confidence interval [CI]: 17.3–25.3) for the EGFR/ALK wild-type group and 21.0 months (95% CI: 15.7–not available [NA]) for the <em>EGFR</em> or <em>ALK</em> mutant group with no difference (<em>p =</em> 0.74). Significant differences occurred in PFS on the basis of PD-L1 expression with values of 13.6 (95% CI: 10.5–NA), 18.7 (95% CI: 15.1–26.9), and 24.7 (95% CI: 20.7–NA) months for TPS of 0, 1–49, and 50 or higher, respectively (<em>p =</em> 0.02).</div></div><div><h3>Conclusions</h3><div>Durvalumab maintenance therapy after definitive CCRT in unresectable locally advanced NSCLC patients with <em>EGFR</em> or <em>ALK</em> mutation demonstrates comparable clinical outcomes to those with wild-type <em>EGFR/ALK</em> when PD-L1 expression is present.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100734"},"PeriodicalIF":3.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653717","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}