JTO Clinical and Research Reports最新文献

{"title":"Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients With Unresectable Advanced or Recurrent NSCLC: An Exploratory Study of J-TAIL","authors":"","doi":"10.1016/j.jtocrr.2024.100683","DOIUrl":"10.1016/j.jtocrr.2024.100683","url":null,"abstract":"<div><h3>Introduction</h3><p>This study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg once every three weeks regimen.</p></div><div><h3>Methods</h3><p>A subgroup of 262 of 1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August 2018 to October 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles 1 to 4, their association with effectiveness, and the association between atezolizumab maximum plasma concentrations (C_max) calculated using the existing PopPK model and AEs of special interest (AESIs).</p></div><div><h3>Results</h3><p>Overall, 175 of 262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (Eastern Cooperative Oncology Group performance status ≥ 2, 12.0%; age ≥ 75 y, 28.9%; atezolizumab as more than or equal to third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 versus Q2 to Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated C_max at cycle 1 increased.</p></div><div><h3>Conclusions</h3><p>In real-world Japanese patients with unresectable advanced/recurrent NSCLC, PKs were similar to previous reports. Certain patient populations had shorter overall survival, and atezolizumab plasma concentrations in cycle 3 were lower in this population. Elevated C_max at cycle 1 may be associated with an increased frequency of AESIs.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 7","pages":"Article 100683"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000535/pdfft?md5=d2642a4e522e6dac6c7d912ac0573717&pid=1-s2.0-S2666364324000535-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141026180","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":"Pathophysiology and Management of Chest Wall Pain after Surgical and Non-Surgical Local Therapies for Lung Cancer","authors":"John Nikitas MD ,&nbsp;Jane Yanagawa MD ,&nbsp;Sandra Sacks MD ,&nbsp;Edward K. Hui MD ,&nbsp;Alan Lee MD ,&nbsp;Jie Deng MD, PhD ,&nbsp;Fereidoun Abtin MD ,&nbsp;Robert Suh MD ,&nbsp;Jay M. Lee MD ,&nbsp;Paul Toste MD ,&nbsp;Bryan M. Burt MD ,&nbsp;Sha’Shonda L. Revels MD ,&nbsp;Robert B. Cameron MD ,&nbsp;Drew Moghanaki MD, MPH","doi":"10.1016/j.jtocrr.2024.100690","DOIUrl":"10.1016/j.jtocrr.2024.100690","url":null,"abstract":"<div><p>Chest wall pain syndromes can emerge following local therapies for lung cancer and can adversely affect patients’ quality-of-life. This can occur after lung surgery, radiation therapy, or percutaneous image-guided thermal ablation. This review describes the multifactorial pathophysiology of chest wall pain syndromes that develop following surgical and non-surgical local therapies for lung cancer and summarizes evidence-based management strategies for inflammatory, neuropathic, myofascial, and osseous pain. It discusses a step-wise approach to treating chest wall pain that begins with non-opioid oral analgesics and includes additional pharmacologic treatments as clinically indicated, such as anticonvulsants, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, and various topical treatments. For myofascial pain, physical medicine techniques, such as acupuncture, trigger point injections, deep tissue massage, and intercostal myofascial release can also offer pain relief. For severe or refractory cases, opioid analgesics, intercostal nerve blocks, or intercostal nerve ablations may be indicated. Fortunately, palliation of treatment-related chest wall pain syndromes can be managed by most clinical providers, regardless of the type of local therapy utilized for a patient’s lung cancer treatment. In cases where a patient’s pain fails to respond to initial medical management, clinicians can consider referring to a pain specialist who can tailor a more specific pharmacologic approach or perform a procedural intervention to relieve pain.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 7","pages":"Article 100690"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000602/pdfft?md5=38240fb7ec1165f21f209d590ceb26a7&pid=1-s2.0-S2666364324000602-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141048998","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":"L2086F Mutant ROS1-Rearranged NSCLC Resistant to Repotrectinib Responds to Cabozantinib: A Case Report","authors":"","doi":"10.1016/j.jtocrr.2024.100673","DOIUrl":"10.1016/j.jtocrr.2024.100673","url":null,"abstract":"<div><p>Repotrectinib, licensed in November 2023, is a novel ROS1 tyrosine kinase inhibitor (TKI) with activity against <em>G2032R</em>, the most common resistance mutation to prior generations of ROS1 TKIs. Here, we report a case of a patient who was heavily pretreated, with advanced <em>L1951R</em> and <em>L2026M</em> mutated <em>ROS1-</em>rearranged NSCLC, who initially responded to repotrectinib but later developed further on-target resistance with the emergence of an <em>L2086F</em> mutation. The disease then responded to cabozantinib, a separate class of ROS1 TKI with preclinical activity against <em>L2086F</em>.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 7","pages":"Article 100673"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000432/pdfft?md5=f04737e16c25c15801d9a2787e2aa0ce&pid=1-s2.0-S2666364324000432-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140773906","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":"Alectinib Versus Crizotinib in Asian Patients With Treatment-Naïve Advanced ALK-Positive NSCLC: Five-Year Update From the Phase 3 ALESIA Study","authors":"Caicun Zhou MD, PhD ,&nbsp;You Lu MD ,&nbsp;Sang-We Kim MD, PhD ,&nbsp;Thanyanan Reungwetwattana MD ,&nbsp;Jianying Zhou MD ,&nbsp;Yiping Zhang MD ,&nbsp;Jianxing He MD, PhD ,&nbsp;Jin-Ji Yang MD ,&nbsp;Ying Cheng MD ,&nbsp;Se-Hoon Lee MD, PhD ,&nbsp;Jianhua Chang MD ,&nbsp;Jian Fang MD ,&nbsp;Zhe Liu PhD ,&nbsp;Lilian Bu MSc ,&nbsp;Li Qian MD ,&nbsp;Tingting Xu MD ,&nbsp;Venice Archer MB ChB, MSc ,&nbsp;Magalie Hilton MSc ,&nbsp;Mingzhu Zhou MSc ,&nbsp;Li Zhang MD","doi":"10.1016/j.jtocrr.2024.100700","DOIUrl":"10.1016/j.jtocrr.2024.100700","url":null,"abstract":"<div><h3>Introduction</h3><p>Previous results from the phase 3 ALESIA study (NCT02838420) revealed that alectinib (a central nervous system [CNS]-active, ALK inhibitor) had clinical benefits in treatment-naïve Asian patients with advanced <em>ALK</em>-positive NSCLC, consistent with the global ALEX study. We present updated data after more than or equal to 5 years of follow-up from the “last patient in” date.</p></div><div><h3>Methods</h3><p>Adult patients with treatment-naïve, advanced <em>ALK</em>-positive NSCLC from mainland China, South Korea, and Thailand were randomized 2:1 to receive twice-daily 600 mg alectinib (n = 125) or 250 mg crizotinib (n = 62). The primary endpoint was investigator-assessed progression-free survival. Secondary or exploratory endpoints included overall survival, objective response rate, time to CNS progression, and safety.</p></div><div><h3>Results</h3><p>At the data cutoff (May 16, 2022), the median survival follow-up was 61 and 51 months in the alectinib and crizotinib arms, respectively. Median progression-free survival was 41.6 months with alectinib versus 11.1 months with crizotinib (stratified hazard ratio = 0.33, 95% confidence interval: 0.23–0.49). Overall survival data remain immature; 5-year overall survival rates were 66.4% (alectinib arm) versus 56.1% (crizotinib arm). Objective response rate was 91.2% versus 77.4% with alectinib and crizotinib, respectively. CNS progression was delayed with alectinib versus crizotinib (cause-specific hazard ratio = 0.16, 95% confidence interval: 0.08–0.32). Median treatment duration was longer with alectinib versus crizotinib (42.3 versus 12.6 mo). No new safety signals were observed.</p></div><div><h3>Conclusions</h3><p>With four additional years of follow-up, these updated results confirm the clinical benefit and manageable safety of alectinib in Asian patients with advanced <em>ALK</em>-positive NSCLC, and confirm alectinib as a standard-of-care treatment for patients with advanced <em>ALK</em>-positive NSCLC.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100700"},"PeriodicalIF":3.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000705/pdfft?md5=8879737d0464e55ddf14baed655ab7b1&pid=1-s2.0-S2666364324000705-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083126","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":"Efficacy and Safety of Anti–Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People’s Republic of China: a Systematic Review and Meta-Analysis","authors":"Qi-An Chen M.B.B.S. ,&nbsp;Kai Ma MD, PhD ,&nbsp;Lin Zhang PhD ,&nbsp;Wei-Hao Lin M.B.B.S. ,&nbsp;Xian-Xian Wu PhD ,&nbsp;Yi-Bo Gao MD, PhD","doi":"10.1016/j.jtocrr.2024.100678","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100678","url":null,"abstract":"<div><h3>Introduction</h3><p>The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti–programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti–PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC.</p></div><div><h3>Methods</h3><p>A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti–PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed.</p></div><div><h3>Results</h3><p>There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (<em>p</em> = 0.80), progression-free survival (<em>p</em> = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (<em>p</em> = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (<em>p</em> = 0.03).</p></div><div><h3>Conclusions</h3><p>Domestic anti–PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti–PD-1/PD-L1 antibodies based on current evidence.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 6","pages":"Article 100678"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000481/pdfft?md5=08d01b2e228c748735ce6ddd0baee1fc&pid=1-s2.0-S2666364324000481-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242790","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-line Osimertinib for Lung Cancer With Uncommon EGFR Exon 19 Mutations and EGFR Compound Mutations","authors":"Tia Cheunkarndee BA,&nbsp;Matthew Z. Guo BA,&nbsp;Stefanie Houseknecht PharmD,&nbsp;Josephine L. Feliciano MD,&nbsp;Christine L. Hann MD, PhD,&nbsp;Vincent K. Lam MD,&nbsp;Benjamin P. Levy MD,&nbsp;Joseph C. Murray MD, PhD,&nbsp;Julie R. Brahmer MD,&nbsp;Patrick M. Forde MBBCh,&nbsp;Kristen A. Marrone MD,&nbsp;Susan C. Scott MD","doi":"10.1016/j.jtocrr.2024.100686","DOIUrl":"10.1016/j.jtocrr.2024.100686","url":null,"abstract":"<div><h3>Introduction</h3><p>Up to 20% of EGFR-mutated NSCLC cases harbor uncommon <em>EGFR</em> mutations, including atypical exon 19 and compound mutations. Relatively little is known about the efficacy of osimertinib in these cases.</p></div><div><h3>Methods</h3><p>Patients treated with first-line osimertinib for NSCLC with rare EGFR exon 19 (non E746_A750del) or compound mutations were included. Response assessment and time to progression were determined using Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Kaplan-Meier analyses were used to estimate progression-free survival (PFS), time to treatment discontinuation (TTD), and overall survival (OS).</p></div><div><h3>Results</h3><p>Thirty-seven patients with NSCLC harboring an atypical EGFR exon 19 mutation or compound mutation were treated with first-line osimertinib at Johns Hopkins from 2016 to 2021. Overall response rate (ORR) was 76% and median PFS, TTD, and OS were 13 months (95% confidence interval [CI]: 10–15), 22 months (95% CI: 17–32) and 36 months (95% CI, 29–48), respectively. Among atypical exon 19 mutations (n = 25), ORR was 80%, median PFS was 12 months (95% CI: 10–15), median TTD was 19 months (95% CI: 17–38), and median OS was 48 months (95% CI: 25–not reached). Compound mutations (n = 12) had an ORR of 67%, median PFS of 14 months (95% CI: 5–22), median TTD of 26 months (95% CI: 5–36), and median OS of 36 months (95% CI: 20–46). Twelve patients (32%) continued first-line osimertinib after local therapy for oligoprogression.</p></div><div><h3>Conclusions</h3><p>Osimertinib exhibited favorable outcomes for rare EGFR exon 19 and compound mutations. The heterogeneity in outcomes among these groups of tumors with similar mutations underscores the need for continued reporting and further study of outcomes among rare variants to optimize management for each patient.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 6","pages":"Article 100686"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000560/pdfft?md5=9d4bd9bd8eab4c733da7e1ae84bfdee1&pid=1-s2.0-S2666364324000560-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141031367","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: Real-World Efficacy and Safety of Sotorasib in U.S. Veterans with KRAS G12C-Mutated NSCLC","authors":"Katherine I. Zhou MD, PhD ,&nbsp;Chenyu Lin MD ,&nbsp;Chin-Lin Tseng MPH ,&nbsp;Nithya Ramnath MBBS ,&nbsp;Jonathan E. Dowell MD ,&nbsp;Michael J. Kelley MD","doi":"10.1016/j.jtocrr.2024.100670","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100670","url":null,"abstract":"<div><h3>Introduction</h3><p>The <em>KRAS</em> G12C inhibitor sotorasib was approved for treating advanced NSCLC in the second line or later on the basis of the CodeBreaK100 trial. Nevertheless, data on the real-world efficacy and safety of sotorasib, and to its optimal dose, remain limited.</p></div><div><h3>Methods</h3><p>Patients treated with sotorasib for NSCLC through the Veterans Health Administration were retrospectively identified from the Corporate Data Warehouse. Survival, response, and toxicity data were obtained from chart review.</p></div><div><h3>Results</h3><p>Among the 128 patients treated with sotorasib through the Veterans Health Administration, objective response rate was 34%, progression-free survival (PFS) six months, and overall survival 12 months. Similar PFS was observed among the 16 patients who received frontline sotorasib without any prior systemic therapy for NSCLC. Toxicity leading to sotorasib interruption or dose reduction occurred in 37% of patients, whereas sotorasib discontinuation for toxicity occurred in 25%. Notably, sotorasib dose reduction was associated with substantially improved PFS and OS.</p></div><div><h3>Conclusions</h3><p>In this real-world study, the observed efficacy of sotorasib was similar to the results of CodeBreaK100. Patients who received frontline sotorasib had similar PFS to our overall cohort, suggesting that first-line sotorasib monotherapy may benefit patients who are not eligible for chemotherapy. Toxicities leading to sotorasib interruption, dose reduction, or discontinuation were common. Sotorasib dose reduction was associated with improved survival, suggesting that sotorasib dose reduction may not compromise efficacy.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 5","pages":"Article 100670"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000407/pdfft?md5=e5df6ae6d2498e5310b4797ba2293166&pid=1-s2.0-S2666364324000407-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894654","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":"BAP1 Deficiency Inflames the Tumor Immune Microenvironment and Is a Candidate Biomarker for Immunotherapy Response in Malignant Pleural Mesothelioma","authors":"Duo Xu MD, PhD ,&nbsp;Yanyun Gao PhD ,&nbsp;Haitang Yang MD, PhD ,&nbsp;Marc Spils MD ,&nbsp;Thomas M. Marti PhD ,&nbsp;Tereza Losmanová MD ,&nbsp;Min Su PhD ,&nbsp;Wenxiang Wang MD ,&nbsp;Qinghua Zhou MD ,&nbsp;Patrick Dorn MD ,&nbsp;Yongqian Shu MD, PhD ,&nbsp;Ren-Wang Peng PhD","doi":"10.1016/j.jtocrr.2024.100672","DOIUrl":"10.1016/j.jtocrr.2024.100672","url":null,"abstract":"<div><h3>Introduction</h3><p>Malignant pleural mesothelioma (MPM) is a rare and universally lethal malignancy with limited treatment options. Immunotherapy with immune checkpoint inhibitors (ICIs) has recently been approved for unresectable MPM, but response to ICIs is heterogeneous, and reliable biomarkers for prospective selection of appropriate subpopulations likely to benefit from ICIs remain elusive.</p></div><div><h3>Methods</h3><p>We performed multiscale integrative analyses of published primary tumor data set from The Cancer Genome Atlas (TCGA) and the French cohort E-MTAB-1719 to unravel the tumor immune microenvironment of MPM deficient in <em>BAP1</em>, one of the most frequently mutated tumor suppressor genes (TSGs) in the disease. The molecular profiling results were validated in independent cohorts of patients with MPM using immunohistochemistry and multiplex immunohistochemistry.</p></div><div><h3>Results</h3><p>We revealed that <em>BAP1</em> deficiency enriches immune-associated pathways in MPM, leading to increased mRNA signatures of interferon alfa/gamma response, activating dendritic cells, immune checkpoint receptors, and T-cell inflammation. This finding was confirmed in independent patient cohorts, where MPM tumors with low BAP1 levels are associated with an inflammatory tumor immune microenvironment characterized by increased exhausted precursor T-cells and macrophages but decreased myeloid-derived suppressor cells (MDSCs). In addition, BAP1^low MPM cells are in close proximity to T cells and therefore can potentially be targeted with ICIs. Finally, we revealed that <em>BAP1</em>-proficient MPM is associated with a hyperactive mitogen-activated protein kinase (MAPK) pathway and may benefit from treatment with MEK inhibitors (MEKis).</p></div><div><h3>Conclusion</h3><p>Our results suggest that BAP1 plays an immunomodulatory role in MPM and that <em>BAP1</em>-deficient MPM may benefit from immunotherapy, which merits further clinical investigation.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 5","pages":"Article 100672"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000420/pdfft?md5=0474ae2ad9f1cfb0a39f806553857fa3&pid=1-s2.0-S2666364324000420-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140398962","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":"Acknowledgment of Reviewers","authors":"","doi":"10.1016/j.jtocrr.2024.100642","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100642","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 5","pages":"Article 100642"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000122/pdfft?md5=24fa93b0c8f77c535159560161ec8932&pid=1-s2.0-S2666364324000122-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141084650","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: Tepotinib as a Treatment Option in MET Exon 14 Skipping-Positive Lung Cancers—Investigating Discordance Between ArcherMET and the Oncomine Dx Target Test","authors":"Yoshihiro Miyashita MD ,&nbsp;Yosuke Hirotsu PhD ,&nbsp;Yuki Nagakubo MS ,&nbsp;Hiroaki Kobayashi MD ,&nbsp;Makoto Kawaguchi MD ,&nbsp;Koki Hata MD ,&nbsp;Ryota Saito MD ,&nbsp;Yumiko Kakizaki MD ,&nbsp;Toshiharu Tsutsui PhD ,&nbsp;Toshio Oyama MD ,&nbsp;Masao Omata MD","doi":"10.1016/j.jtocrr.2024.100679","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100679","url":null,"abstract":"<div><h3>Introduction</h3><p>NSCLC is a leading cause of cancer-related mortality worldwide. Specific genetic alterations, such as <em>MET</em> exon 14 (<em>MET</em>ex14) skipping, have been identified in NSCLC, allowing targeted therapy. Tepotinib, a highly selective MET inhibitor, has displayed promise in patients with advanced NSCLC. Nevertheless, challenges arise when identifying treatment strategies for patients with discordant results regarding <em>MET</em>ex14 skipping detection between diagnostic tests.</p></div><div><h3>Methods</h3><p>We investigated patients with NSCLC and discordant results for <em>MET</em>ex14 skipping between the Oncomine Dx Target Test (ODxTT) and ArcherMET. Clinical response, adverse events, and the duration of tepotinib treatment were assessed, and statistical analysis was performed.</p></div><div><h3>Results</h3><p>Among the 19 patients deemed <em>MET</em>ex14 skipping positive by ODxTT, only 10 had concordant results with ArcherMET. The number of <em>MET</em>ex14 skipping reads detected by ODxTT was significantly lower in discordant cases. Of the 19 patients, 14 received tepotinib, and comparable response and disease control rates were observed in both concordant and discordant cases. The duration of treatment did not significantly differ between the two groups.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that tepotinib has comparable therapeutic effects in patients with <em>MET</em>ex14 skipping-positive NSCLC irrespective of the concordance of results between ODxTT and ArcherMET. Tepotinib is a possible treatment option for patients with <em>MET</em>ex14 skipping, even in patients with discordant test results.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 6","pages":"Article 100679"},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000493/pdfft?md5=536c840b02b0e446a642a151aad3d799&pid=1-s2.0-S2666364324000493-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156387","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}