JTO Clinical and Research Reports最新文献

{"title":"RET Fusion Testing in Patients With NSCLC: The RETING Study","authors":"Esther Conde MD, PhD ,&nbsp;Susana Hernandez PhD ,&nbsp;Jose Luis Rodriguez Carrillo MD ,&nbsp;Rebeca Martinez APT ,&nbsp;Marta Alonso APT ,&nbsp;Daniel Curto MD ,&nbsp;Beatriz Jimenez MD ,&nbsp;Alejandra Caminoa MD, PhD ,&nbsp;Amparo Benito MD ,&nbsp;Pilar Garrido MD, PhD ,&nbsp;Sergi Clave PhD ,&nbsp;Edurne Arriola MD, PhD ,&nbsp;Isabel Esteban-Rodriguez MD, PhD ,&nbsp;Javier De Castro MD, PhD ,&nbsp;Irene Sansano MD ,&nbsp;Enriqueta Felip MD, PhD ,&nbsp;Federico Rojo MD, PhD ,&nbsp;Manuel Dómine MD, PhD ,&nbsp;Ihab Abdulkader MD, PhD ,&nbsp;Jorge Garcia-Gonzalez MD ,&nbsp;Fernando Lopez-Rios MD, PhD","doi":"10.1016/j.jtocrr.2024.100653","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100653","url":null,"abstract":"<div><h3>Introduction</h3><p><em>RET</em> inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identification of <em>RET</em> fusions remains a difficult challenge. Most guidelines encourage the upfront use of next-generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect <em>RET</em> fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC.</p></div><div><h3>Methods</h3><p>This situation prompted us to evaluate several <em>RET</em> assays in a large multicenter cohort of <em>RET</em> fusion–positive NSCLC (n = 38) to obtain real-world data. In addition to RNA-based NGS (the criterion standard method), all positive specimens underwent break-apart <em>RET</em> FISH with two different assays and were also tested by an RT-PCR assay.</p></div><div><h3>Results</h3><p>The most common <em>RET</em> partners were <em>KIF5B</em> (78.9%), followed by <em>CCDC6</em> (15.8%). The two <em>RET</em> NGS-positive but FISH-negative samples contained a <em>KIF5B(15)-RET(12)</em> fusion. The three <em>RET</em> fusions not identified with RT-PCR were <em>AKAP13(35)-RET(12)</em>, <em>KIF5B(24)-RET(9)</em> and <em>KIF5B(24)-RET(11)</em>. All three false-negative RT-PCR cases were FISH-positive, exhibited a typical break-apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively).</p></div><div><h3>Conclusions</h3><p>In-depth knowledge of the advantages and disadvantages of the different <em>RET</em> testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of <em>RET</em> fusions in patients with NSCLC. The likelihood of <em>RET</em> false-negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100653"},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000237/pdfft?md5=1d0484197557d1fce0d0732e03259f18&pid=1-s2.0-S2666364324000237-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141940","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":"Osimertinib Plasma Trough Concentration in Relation to Brain Metastases Development in Patients With Advanced EGFR-Mutated NSCLC","authors":"Judith L. Gulikers MSc ,&nbsp;G.D. Marijn Veerman MD, PhD ,&nbsp;Merel Jebbink MD, PhD ,&nbsp;Paul D. Kruithof PharmD ,&nbsp;Christi M.J. Steendam MD, PhD ,&nbsp;René J. Boosman PhD ,&nbsp;Ron H.J. Mathijssen MD, PhD ,&nbsp;Vivianne C.G. Tjan-Heijnen MD, PhD ,&nbsp;Johanna H.M. Driessen PhD ,&nbsp;Safiye Dursun MD ,&nbsp;Egbert F. Smit MD, PhD ,&nbsp;Anne-Marie C. Dingemans MD, PhD ,&nbsp;Robin M.J.M. van Geel PharmD, PhD ,&nbsp;Sander Croes PharmD, PhD ,&nbsp;Lizza E.L. Hendriks MD, PhD","doi":"10.1016/j.jtocrr.2024.100656","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100656","url":null,"abstract":"<div><h3>Introduction</h3><p>Brain metastases (BM) are common in patients with advanced <em>EGFR</em>-mutated (<em>EGFR</em>m+) NSCLC. Despite good BM-related outcomes of osimertinib, several patients still experience intracranial progression. A possible explanation is pharmacologic failure due to low plasma trough levels (C_min,SS) and consequently limited intracranial osimertinib exposure. We investigated the relation between osimertinib C_min,SS and BM development or progression.</p></div><div><h3>Methods</h3><p>A prospective multicenter cohort study, including patients receiving osimertinib for advanced <em>EGFR</em>m<em>+</em> NSCLC. At osimertinib start, patients were allocated to the BM or no or unknown BM cohort and were further divided into subgroups based on osimertinib C_min,SS (low, middle, and high exposure). Cumulative incidence of BM progression or development and overall survival were determined for each group.</p></div><div><h3>Results</h3><p>A total of 173 patients were included, with 49 (28.3%) had baseline BM. Of these patients, 36.7% experienced BM progression, of which 16.7% in the low (&lt;159.3 ng/mL), 40.0% in the middle, and 47.1% in the high (&gt;270.7 ng/mL) C_min,SS subgroups. After 12 months, the cumulative incidence of BM progression for the BM cohort was 20% (95% confidence interval [CI] 2.6–49.0), 31% (95% CI:10.6–53.9), and 31% (95% CI:10.8–54.5) per C_min,SS subgroup, respectively. After 20 months, this was 20% (95% CI:2.6–49.0), 52% (95% CI:23.8–74.2), and 57% (95% CI:24.9–79.7), respectively. For the no or unknown BM cohort, 4.0% developed BM without differences within C_min,SS subgroups.</p></div><div><h3>Conclusions</h3><p>No relation was found between osimertinib C_min,SS and BM development or progression in patients with advanced <em>EGFR</em>m<em>+</em> NSCLC. This suggests that systemic osimertinib exposure is not a surrogate marker for BM development or progression.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100656"},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000262/pdfft?md5=a80aff0e7fabe98c2bffb809b20caea9&pid=1-s2.0-S2666364324000262-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140180174","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":"Immunotherapy With Radiotherapy for Brain Metastases in Patients With NSCLC: NEJ060","authors":"Takehiro Tozuka MD ,&nbsp;Yuji Minegishi MD, PhD ,&nbsp;Ou Yamaguchi MD, PhD ,&nbsp;Kana Watanabe MD ,&nbsp;Yukihiro Toi MD ,&nbsp;Ryota Saito MD, PhD ,&nbsp;Yoshiaki Nagai MD, PhD ,&nbsp;Yosuke Tamura MD, PhD ,&nbsp;Tetsuaki Shoji MD, PhD ,&nbsp;Haruka Odagiri MD ,&nbsp;Noriyuki Ebi MD ,&nbsp;Kosuke Sakai MD, PhD ,&nbsp;Nobuhiro Kanaji MD, PhD ,&nbsp;Makoto Izumi MD ,&nbsp;Sayo Soda MD, PhD ,&nbsp;Satoshi Watanabe MD, PhD ,&nbsp;Satoshi Morita PhD ,&nbsp;Kunihiko Kobayashi MD, PhD ,&nbsp;Masahiro Seike MD, PhD","doi":"10.1016/j.jtocrr.2024.100655","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100655","url":null,"abstract":"<div><h3>Introduction</h3><p>Immune checkpoint inhibitor (ICI)–based treatment has become standard treatment for patients with advanced NSCLC. We aimed to determine the survival benefit of upfront radiotherapy for brain metastases (BMs) in patients with NSCLC who received ICI alone (ICI-alone) or with chemotherapy (ICI-chemo).</p></div><div><h3>Methods</h3><p>This study included consecutive patients with NSCLC having BMs who received ICI alone or ICI-chemo at 50 institutes between February 2017 and September 2021. The presence of BMs was confirmed by imaging before treatment. Treatment outcomes were compared between patients who did and did not receive upfront radiotherapy for BMs. Potential confounding factors were adjusted between the groups through inverse probability treatment weighting (IPTW) analysis and overlap weighting (OW) analysis with propensity scores.</p></div><div><h3>Results</h3><p>Patients were grouped as ICI-alone cohort, 224 patients (upfront-radiotherapy group, 135 patients; no-radiotherapy group, 89 patients) and ICI-chemo cohort, 367 patients (upfront-radiotherapy group, 212 patients; no-radiotherapy group, 155 patients). In the ICI-alone cohort, the overall survival of the upfront-radiotherapy group was significantly longer than that of the no-radiotherapy group (IPTW-adjusted hazards ratio [HR] = 0.45 [95% confidence interval [CI]: 0.29–0.72], OW-adjusted HR = 0.52 [95% CI: 0.35–0.77]). In contrast, in the ICI-chemo cohort, the OS of the upfront-radiotherapy group was not significantly different from that of the no-radiotherapy group (IPTW-adjusted HR = 1.02 [95% CI: 0.70–1.48], OW-adjusted HR = 0.93 [95% CI: 0.65–1.33]).</p></div><div><h3>Conclusions</h3><p>Upfront radiotherapy for BMs was associated with longer overall survival in patients with NSCLC who received ICI alone; however, it did not exhibit survival benefits in the patients who received ICI-chemo.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100655"},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000250/pdfft?md5=347b3200c1c497c4800c5752fb07e40f&pid=1-s2.0-S2666364324000250-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140163116","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":"Adenocarcinoma Harboring EGFR-RAD51 Fusion Treated With Osimertinib: A Case Report","authors":"Sunny Y. Lai MD,&nbsp;Noah H. Richardson MD,&nbsp;Mya Tran PharmD,&nbsp;Nasser H. Hanna MD,&nbsp;Misty D. Shields MD, PhD","doi":"10.1016/j.jtocrr.2024.100652","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100652","url":null,"abstract":"<div><p><em>EGFR</em> mutations are among the most common driver mutations in lung adenocarcinoma. Rare alterations, such as the <em>EGFR-RAD51</em> fusion, respond to treatment with EGFR tyrosine kinase inhibitors but can be missed by limited genomic sequencing panels. Here, we report a case of metastatic lung adenocarcinoma in a never-smoker patient who initially did not have a targetable alteration identified on two different sequencing panels. The initial response to combination chemoimmunotherapy was short-lived. A rare <em>EGFR-RAD51</em> fusion was then identified using a more in-depth sequencing panel. The patient experienced a dramatic and durable response to osimertinib. This case highlights the rarity of <em>EGFR-RAD51</em> fusions, the efficacy of EGFR tyrosine kinase inhibitors, and the importance of a thorough search for targetable alterations in never-smokers with lung adenocarcinoma.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100652"},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000225/pdfft?md5=6fe60be7fd389bf5543280384dcab5de&pid=1-s2.0-S2666364324000225-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141824","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":"Cabozantinib Response in a Patient With NSCLC Harboring Both MET Exon 14 Skipping Mutation and Secondary RET Fusion: A Case Report","authors":"Carlos Torrado MD ,&nbsp;Jamie Feng MD, FRCPC ,&nbsp;Elizabeth Faour MD, FRCPC ,&nbsp;Natasha B. Leighl MD, MMSc, FRCPC, FASCO","doi":"10.1016/j.jtocrr.2024.100647","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100647","url":null,"abstract":"<div><p>MET exon 14 skipping mutation has emerged as a new oncogenic driver in NSCLC with available targeted therapies, including Food and Drug Administration–approved inhibitors capmatinib and tepotinib. Potential resistance mechanisms are beginning to be described and include several on-target and off-target mutations. Here, we report an emergent secondary RET fusion in a patient with a primary MET exon 14 skipping mutation that progressed on capmatinib after the initial response. Subsequently, this patient received both a RET inhibitor (selpercatinib) followed by another MET-targeted treatment (tepotinib) without clinical benefit. Thereafter, cabozantinib, a multikinase inhibitor with activity against RET and MET was started with a rapid clinical and radiologic benefit.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 4","pages":"Article 100647"},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000171/pdfft?md5=873c3988b4ea93bcebc85f563c2e0064&pid=1-s2.0-S2666364324000171-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195513","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":"Health Services Access Inequalities in Brazil Result in Poorer Outcomes for Stage III NSCLC—RELANCE/LACOG 0118","authors":"Vladmir C. Cordeiro de Lima MD, PhD ,&nbsp;Ana Gelatti MD, MSc ,&nbsp;José F.P. Moura MD, PhD ,&nbsp;Aline F. Fares MD, MSc ,&nbsp;Gilberto de Castro Jr. MD, PhD ,&nbsp;Clarissa Mathias MD, PhD ,&nbsp;Ricardo M. Terra MD, PhD ,&nbsp;Gustavo Werutsky MD, PhD ,&nbsp;Marcelo Corassa MD ,&nbsp;Luiz Henrique L. Araújo MD, PhD ,&nbsp;Eduardo Cronenberger MD, MSc ,&nbsp;Fernanda K. Fujiki MD ,&nbsp;Sandro Reichow MD ,&nbsp;Antônio Vinícius T. da Silva MD ,&nbsp;Tércia V. Reis MD ,&nbsp;Mônica Luciana A. Padoan MD ,&nbsp;Patrícia Pacheco MD ,&nbsp;Rosely Yamamura MD ,&nbsp;Caroline Kawamura MD ,&nbsp;Eldsamira Mascarenhas MD, MSc ,&nbsp;Clarissa Baldotto MD, PhD","doi":"10.1016/j.jtocrr.2024.100646","DOIUrl":"10.1016/j.jtocrr.2024.100646","url":null,"abstract":"<div><h3>Introduction</h3><p>Stage III NSCLC is a heterogeneous disease, representing approximately one-third of newly diagnosed lung cancers. Brazil lacks detailed information regarding stage distribution, treatment patterns, survival, and prognostic variables in locally advanced NSCLC.</p></div><div><h3>Methods</h3><p>RELANCE/LACOG 0118 is an observational, retrospective cohort study assessing sociodemographic and clinical data of patients diagnosed with having stage III NSCLC from January 2015 to June 2019, regardless of treatment received. The study was conducted across 13 cancer centers in Brazil. Disease status and survival data were collected up to June 2021. Descriptive statistics, survival analyses, and a multivariable Cox regression model were performed. <em>p</em> values less than 0.05 were considered significant.</p></div><div><h3>Results</h3><p>We recruited 403 patients with stage III NSCLC. Most were male (64.0%), White (31.5%), and smokers or former smokers (86.1%). Most patients had public health insurance (67.5%), had stage IIIA disease (63.2%), and were treated with concurrent chemoradiation (53.1%). The median follow-up time was 33.83 months (95% confidence interval [CI]: 30.43–37.50). Median overall survival (OS) was 27.97 months (95% CI: 21.57–31.73), and median progression-free survival was 11.23 months (95% CI: 10.70–12.77). The type of treatment was independently associated with OS and progression-free survival, whereas the types of health insurance and histology were independent predictors of OS only.</p></div><div><h3>Conclusions</h3><p>Brazilian patients with stage III NSCLC with public health insurance are diagnosed later and have poorer OS. Nevertheless, patients with access to adequate treatment have outcomes similar to those reported in the pivotal trials. Health policy should be improved to make lung cancer diagnosis faster and guarantee prompt access to adequate treatment in Brazil.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 3","pages":"Article 100646"},"PeriodicalIF":0.0,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266636432400016X/pdfft?md5=57c47047bb2b8edb7d9c4b08d8eae3c3&pid=1-s2.0-S266636432400016X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139686193","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":"Adjuvant Osimertinib in Patients With Stage IB to IIIA EGFR Mutation-Positive NSCLC After Complete Tumor Resection: ADAURA China Subgroup Analysis","authors":"Jie Wang MD, PhD ,&nbsp;Yi-Long Wu MD ,&nbsp;Shun Lu MD, PhD ,&nbsp;Qun Wang MD ,&nbsp;Shanqing Li MD ,&nbsp;Wen-Zhao Zhong MD, PhD ,&nbsp;Qiming Wang MD ,&nbsp;Wei Li MD, PhD ,&nbsp;Buhai Wang MD ,&nbsp;Jun Chen MD ,&nbsp;Ying Cheng MD ,&nbsp;Hongbing Duan MD ,&nbsp;Gaofeng Li MD ,&nbsp;Li Shan MD ,&nbsp;Yangbo Liu MS ,&nbsp;Jing Liu MD ,&nbsp;Xiangning Huang PhD ,&nbsp;Ana Bolanos MD ,&nbsp;Jie He MD, PhD","doi":"10.1016/j.jtocrr.2023.100621","DOIUrl":"10.1016/j.jtocrr.2023.100621","url":null,"abstract":"<div><h3>Introduction</h3><p>In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People’s Republic of China from ADAURA.</p></div><div><h3>Methods</h3><p>In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety.</p></div><div><h3>Results</h3><p>Of 682 patients enrolled globally, 159 patients in the People’s Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13–0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17–0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21–1.20). HRQoL was maintained from baseline, and safety was consistent with the global population.</p></div><div><h3>Conclusions</h3><p>In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100621"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001649/pdfft?md5=d4f2a9fa8b3722f16b49539d74f835e2&pid=1-s2.0-S2666364323001649-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138988523","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":"The Efficacy and Safety of Treating Acquired MET Resistance Through Combinations of Parent and MET Tyrosine Kinase Inhibitors in Patients With Metastatic Oncogene-Driven NSCLC","authors":"Tejas Patil MD ,&nbsp;Alyse Staley MS ,&nbsp;Yunan Nie MD ,&nbsp;Mandy Sakamoto MD ,&nbsp;Margaret Stalker MD ,&nbsp;James M. Jurica MD, MBA ,&nbsp;Kenna Koehler BA ,&nbsp;Amanda Cass PharmD ,&nbsp;Halle Kuykendall BA ,&nbsp;Emily Schmitt MS ,&nbsp;Emma Filar BA ,&nbsp;Evelina Reventaite MS ,&nbsp;Kurt D. Davies PhD ,&nbsp;Hala Nijmeh PhD ,&nbsp;Mary Haag PhD ,&nbsp;Benjamin A. Yoder PharmD ,&nbsp;Paul A. Bunn MD ,&nbsp;Erin L. Schenk MD, PhD ,&nbsp;Dara L. Aisner MD, PhD ,&nbsp;Wade T. Iams MD ,&nbsp;D. Ross Camidge MD, PhD","doi":"10.1016/j.jtocrr.2024.100637","DOIUrl":"10.1016/j.jtocrr.2024.100637","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Acquired &lt;em&gt;MET&lt;/em&gt; gene amplification, &lt;em&gt;MET&lt;/em&gt; exon 14 skip mutations, or &lt;em&gt;MET&lt;/em&gt; fusions can emerge as resistance mechanisms to tyrosine kinase inhibitors (TKIs) in patients with lung cancer. The efficacy and safety of combining MET TKIs (such as crizotinib, capmatinib, or tepotinib) with parent TKIs to target acquired MET resistance are not well characterized.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Multi-institutional retrospective chart review identified 83 patients with metastatic oncogene-driven NSCLC that were separated into the following two pairwise matched cohorts: (1) MET cohort (n = 41)—patients with acquired MET resistance continuing their parent TKI with a MET TKI added or (2) Chemotherapy cohort (n = 42)—patients without any actionable resistance continuing their parent TKI with a platinum-pemetrexed added. Clinicopathologic features, radiographic response (by means of Response Evaluation Criteria in Solid Tumors version 1.1), survival outcomes, adverse events (AEs) (by means of Common Terminology Criteria for Adverse Events version 5.0), and genomic data were collected. Survival outcomes were assessed using Kaplan-Meier methods. Multivariate modeling adjusted for lines of therapy, brain metastases, TP53 mutations, and oligometastatic disease.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Within the MET cohort, median age was 56 years (range: 36–83 y). Most patients were never smokers (28 of 41, 68.3%). Baseline brain metastases were common (21 of 41, 51%). The most common oncogenes in the MET cohort were &lt;em&gt;EGFR&lt;/em&gt; (30 of 41, 73.2%), &lt;em&gt;ALK&lt;/em&gt; (seven of 41, 17.1%), and &lt;em&gt;ROS1&lt;/em&gt; (two of 41, 4.9%). Co-occurring TP53 mutations (32 of 41, 78%) were frequent. Acquired MET alterations included &lt;em&gt;MET&lt;/em&gt; gene amplification (37 of 41, 90%), MET exon 14 mutations (two of 41, 5%), and &lt;em&gt;MET&lt;/em&gt; gene fusions (two of 41, 5%). After multivariate adjustment, the objective response rate (ORR) was higher in the MET cohort versus the chemotherapy cohort (ORR: 69.2% versus 20%, &lt;em&gt;p&lt;/em&gt; &lt; 0.001). Within the MET cohort, &lt;em&gt;MET&lt;/em&gt; gene copy number (≥10 versus 6–10) did not affect radiographic response (54.5% versus 68.4%, &lt;em&gt;p&lt;/em&gt; = 0.698). There was no difference in ORR on the basis of MET TKI used (F [2, 36] = 0.021, &lt;em&gt;p&lt;/em&gt; = 0.978). There was no difference in progression-free survival (5 versus 6 mo; hazard ratio = 0.64; 95% confidence interval: 0.34–1.23, &lt;em&gt;p&lt;/em&gt; = 0.18) or overall survival (13 versus 11 mo; hazard ratio = 0.75; 95% confidence interval: 0.42–1.35, &lt;em&gt;p&lt;/em&gt; = 0.34) between the MET and chemotherapy cohorts. In the MET cohort, dose reductions for MET TKI-related toxicities were common (17 of 41, 41.4%) but less frequent for parent TKIs (two of 41, 5%). Grade 3 AEs were not significant between crizotinib, capmatinib, and tepotinib (&lt;em&gt;p&lt;/em&gt; = 0.3). The discontinuation rate of MET TKIs was 17% with no significant differences between MET TKIs (&lt;em&gt;p&lt;/em&gt; = 0.315). Among pre- a","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100637"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000079/pdfft?md5=02edf03acc380586e7f2e154541cebf4&pid=1-s2.0-S2666364324000079-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139639289","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":"Program-Based Lung Cancer Care: A Prospective Observational Tumor Registry Linkage Study","authors":"Wei Liao PhD ,&nbsp;Meredith Ray PhD ,&nbsp;Carrie Fehnel BBA ,&nbsp;Jordan Goss MA ,&nbsp;Catherine J. Shepherd MFA ,&nbsp;Anita Patel MHA ,&nbsp;Talat Qureshi BS ,&nbsp;Federico Caro BA ,&nbsp;Jessica Roma AS ,&nbsp;Anna Derrick AA ,&nbsp;Anberitha T. Matthews PhD ,&nbsp;Nicholas R. Faris M. Div ,&nbsp;Matthew Smeltzer PhD ,&nbsp;Raymond U. Osarogiagbon M.B.B.S., FACP","doi":"10.1016/j.jtocrr.2023.100629","DOIUrl":"10.1016/j.jtocrr.2023.100629","url":null,"abstract":"<div><h3>Introduction</h3><p>Low-dose computed tomography screening (LDCT) and lung nodule programs (LNP) promote early lung cancer detection, improve survival; Multidisciplinary Care Programs (MDC) promote guideline-concordant care. The impact of such program-based care on “real-world” lung cancer survival is unquantified. We evaluated outcomes of lung cancer care delivered through structured programs in a community health care system.</p></div><div><h3>Methods</h3><p>We conducted a cohort study linking institutional prospective observational LDCT, LNP and MDC databases with Tumor Registry of Baptist Cancer Center facilities. We categorized all patients diagnosed with lung cancer between 2011 and 2021 into program-based care versus non-program-based care cohorts. We compared patient characteristics, stage distribution, treatment modalities, survival and mortality in each pathway of care.</p></div><div><h3>Results</h3><p>Of 12,148 patients, 237, 1,165, 1,140 and 9,606 were diagnosed through the LDCT, LNP, MDC or no program, respectively; non-program-based care sequentially diminished from 96.3% to 66.5%, diagnosis through LDCT increased from 0.5% to 7.1%, LNP from 3.5% to 20.8%; and MDC alone decreased from a high of 12.8% in 2014 to 5.6% in 2021. Program-based care was associated with earlier stage (p &lt; 0.001), higher surgical resection rates (<em>p</em> &lt; 0.001), greater use of adjuvant therapy (<em>p</em> &lt; 0.001), better aggregate and stage-stratified survival (<em>p</em> &lt; 0.001), and lower all-cause and lung cancer-specific mortality (<em>p</em> &lt; 0.001). Recipients of non-program-based care were considerably less likely to receive lung cancer treatment; results remained consistent when patients receiving no treatment were excluded.</p></div><div><h3>Conclusions</h3><p>Program-based care was associated with substantially better survival. Increasing access to program-based care should be explored as a matter of urgent public policy.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100629"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001728/pdfft?md5=7ab7677cbe150ebddf7b7d191080ff6f&pid=1-s2.0-S2666364323001728-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139195392","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":"Targeting MET in NSCLC: An Ever-Expanding Territory","authors":"Ying Han MD ,&nbsp;Yinghui Yu MD ,&nbsp;Da Miao MD ,&nbsp;Mo Zhou MD ,&nbsp;Jing Zhao MD ,&nbsp;Zhehua Shao MD, PhD ,&nbsp;Rui Jin MD ,&nbsp;Xiuning Le MD, PhD ,&nbsp;Wen Li MD ,&nbsp;Yang Xia MD, PhD","doi":"10.1016/j.jtocrr.2023.100630","DOIUrl":"10.1016/j.jtocrr.2023.100630","url":null,"abstract":"<div><p>MET protooncogene (MET) alterations are known driver oncogenes in NSCLC. Since the identification of MET as a potential therapeutic target, extensive clinical trials have been performed. As a result, MET-targeted therapies, including MET tyrosine kinase inhibitors, monoclonal antibodies, and MET antibody–drug conjugates now play important roles in the standard treatment of MET-altered NSCLC; they have considerably improved the outcomes of patients with tumors that harbor MET oncogenic drivers. Although clinical agents are currently available and numerous other options are in development, particular challenges in the field require attention. For example, the therapeutic efficacy of each drug remains unsatisfactory, and concomitantly, the resistance mechanisms are not fully understood. Thus, there is an urgent need for optimal drug sequencing and combinations, along with a thorough understanding of treatment resistance. In this review, we describe the current landscape of pertinent clinical trials focusing on MET-targeted strategies and discuss future developmental directions in this rapidly expanding field.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100630"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266636432300173X/pdfft?md5=1889087d20e3ec65ca7ef169c2b8c133&pid=1-s2.0-S266636432300173X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139393626","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}