JTO Clinical and Research Reports最新文献

{"title":"Synchronous Oligometastasis and Oligoprogression as a Prognostic Marker in Patients With Extensive-Stage SCLC Treated With a Combination of Immune-Checkpoint Inhibitor and Chemotherapy (HOT2301)","authors":"Kana Hashimoto MD ,&nbsp;Daisuke Morinaga MD ,&nbsp;Hajime Asahina MD, PhD ,&nbsp;Mina Ishidoya MD ,&nbsp;Hajime Kikuchi MD, PhD ,&nbsp;Hiroshi Yokouchi MD, PhD ,&nbsp;Toshiyuki Harada MD, PhD ,&nbsp;Osamu Honjo MD ,&nbsp;Ryota Shigaki MD ,&nbsp;Taichi Takashina MD, PhD ,&nbsp;Yuka Fujita MD, PhD ,&nbsp;Mamoru Takahashi MD, PhD ,&nbsp;Yasutaka Kawai MD ,&nbsp;Ryotaro Kida MD ,&nbsp;Kenichiro Ito MD ,&nbsp;Noriaki Sukoh MD, PhD ,&nbsp;Ayumu Takahashi MD, PhD ,&nbsp;Fumihiro Hommura MD, PhD ,&nbsp;Yoshihito Ohhara MD, PhD ,&nbsp;Megumi Furuta MD, PhD ,&nbsp;Satoshi Oizumi MD, PhD","doi":"10.1016/j.jtocrr.2024.100715","DOIUrl":"10.1016/j.jtocrr.2024.100715","url":null,"abstract":"<div><h3>Introduction</h3><div>Oligometastasis and oligoprogression (OP) has not been adequately defined in extensive-stage SCLC (ES-SCLC) and may be a good indication for adding local treatment. Therefore, this multicenter study aimed to investigate the prognostic impact of oligometastasis and OP in ES-SCLC.</div></div><div><h3>Methods</h3><div>We enrolled patients who received chemoimmunotherapy between September 2019 and June 2022. Patients were classified into oligometastasis and non-oligometastasis groups by determining the number of original tumor lesions and distant metastases (worsening or newly appearing lesions) at the time of initial diagnosis and disease progression after first-line treatment.</div></div><div><h3>Results</h3><div>We retrospectively analyzed 265 consecutive patients with ES-SCLC. Synchronous oligometastasis (SOM) and OP was defined as less than or equal to five lesions in less than or equal to two organs, including lungs; 21.0% and 53.2% of patients had SOM and OP, respectively. Median progression-free survival was 5.8 months and 4.9 months in patients with and without SOM, respectively (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.51–1.02, <em>p</em> = 0.065). Median overall survival was 20.5 months and 15.0 months in patients with and without SOM (HR = 0.58, 95% CI: 0.37–0.95, <em>p</em> = 0.027) from the initiation of first-line treatment. The OP group revealed a better progression-free survival of 5.2 months (versus 3.2 mo, HR = 0.69, 95% CI: 0.50–0.96, <em>p</em> = 0.026) and overall survival of 15.1 months (versus 7.5 mo, HR = 0.44, 95% CI: 0.29–0.66, <em>p</em> = 0.027) from the initiation of second-line treatment compared with the non-OP group. The Lung Immune Prognostic Index score was significantly lower in the SOM and OP group.</div></div><div><h3>Conclusions</h3><div>ES-SCLC in patients with SOM and OP may be more indolent than that of the nonoligometastasis group, therefore, new treatment strategies, including the addition of local treatment, should be explored.</div></div><div><h3>Clinical trial registration</h3><div>This study was registered at UMIN-CTR (UMIN000053402).</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100715"},"PeriodicalIF":3.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358681","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 Whole Picture of First-Line Osimertinib for EGFR Mutation-Positive Advanced NSCLC: Real-World Efficacy, Safety, Progression Pattern, and Posttreatment Therapy (Reiwa Study)","authors":"Kageaki Watanabe MD ,&nbsp;Yukio Hosomi MD, PhD ,&nbsp;Katsuhiko Naoki MD, PhD ,&nbsp;Yoshiro Nakahara MD, PhD ,&nbsp;Yoko Tsukita MD, PhD ,&nbsp;Hirotaka Matsumoto MD, PhD ,&nbsp;Kiyotaka Yoh MD ,&nbsp;Yasuhito Fujisaka MD, PhD ,&nbsp;Satoshi Takahashi MD, PhD ,&nbsp;Saori Takata MD, PhD ,&nbsp;Kazuhiro Usui MD, PhD ,&nbsp;Kazuma Kishi MD, PhD ,&nbsp;Go Naka MD, PhD ,&nbsp;Shu Tamano MSS ,&nbsp;Kohei Uemura PhD ,&nbsp;Hideo Kunitoh MD, PhD","doi":"10.1016/j.jtocrr.2024.100720","DOIUrl":"10.1016/j.jtocrr.2024.100720","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib is used as the first-line treatment for EGFR mutation-positive NSCLC. Nevertheless, its efficacy and safety in clinical practice remain to be fully elucidated and the pattern of progression and the optimal subsequent treatment after osimertinib remains unclear.</div></div><div><h3>Methods</h3><div>This was a multicenter prospective observational study. EGFR mutation-positive patients with NSCLC who started first-line osimertinib from September 2018 to August 2020 were enrolled and followed up until August 2022.</div></div><div><h3>Results</h3><div>A total of 583 patients received osimertinib. The median progression-free and overall survival were 20.0 (95% confidence interval [CI]: 17.6–21.7) months and 41.0 (95% CI: 37.1–44.1) months, respectively. Grade 3 or worse adverse events were observed in 136 patients (23.3%). Progression patterns were categorized as central nervous system only, oligo-progression, and multiple organs on the basis of the Response Evaluation Criteria in Solid Tumors—progressive disease and occurred in 37 (10.8%), 156 (45.4%), and 151 patients (43.9%). The patient’s condition on progression was asymptomatic in 195 patients (56.7%). Osimertinib was continued in 163 patients (47.4%) after confirming progression. In clinically stable population with progressive disease (n = 247), survival after progression was 13.3 (95% CI: 10.9–16.4) months for those who continued osimertinib beyond progressive disease (n = 124), and 24.1 (95% CI: 17.7–34.0) months for those who discontinued osimertinib (n = 123) (hazard ratio = 2.01, 95% CI: 1.38–2.91, <em>p</em> = 0.0002). Platinum plus pemetrexed had the best overall survival benefits after osimertinib.</div></div><div><h3>Conclusions</h3><div>First-line osimertinib was found to have good effectiveness comparable to that reported in pivotal studies. Nevertheless, osimertinib should be discontinued among those who develop progression.</div></div><div><h3>Trial registration number</h3><div>UMIN000038683</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100720"},"PeriodicalIF":3.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426750","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":"ALKTERNATE: A Pilot Study Alternating Lorlatinib With Crizotinib in ALK-Positive NSCLC With Prior ALK Inhibitor Resistance","authors":"Malinda Itchins BMedSci, M.B.B.S., FRACP, PhD ,&nbsp;Shirley Liang BSc ,&nbsp;Chris Brown MBiostats, BSc ,&nbsp;Tristan Barnes BSc (Med), M.B.B.S., FRACP ,&nbsp;Gavin Marx BSc, M.B.B.S., FRACP ,&nbsp;Venessa Chin M.B.B.S., FRACP, PhD ,&nbsp;Steven Kao BHB, MBChB, PhD, FRACP ,&nbsp;Po Yee Yip MBChB, FRACP, PhD ,&nbsp;Antony J. Mersiades BMedSc, M.B.B.S., FRACP, MMed (Clin. Epi) ,&nbsp;Adnan Nagrial M.B.B.S., FRACP, PhD ,&nbsp;Victoria Bray M.B.B.S., FRACP, PhD ,&nbsp;Geoffrey Peters BPharm, M.B.B.S., FRACP ,&nbsp;Sagun Parakh BSc, MBChB, FRACP, PhD ,&nbsp;Kavita Garg PhD ,&nbsp;Bob T. Li MD, PhD, MPH ,&nbsp;Matthew McKay PhD ,&nbsp;Kenneth O'Byrne M.B.B.S., FRACP, FRCPA, MD ,&nbsp;Thomas John M.B.B.S., FRACP, PhD ,&nbsp;Anthony J. Gill MD, FRCPA ,&nbsp;Mark P. Molloy PhD ,&nbsp;Nick Pavlakis BSc, M.B.B.S., MMed (Clin. Epi), PhD, FRACP","doi":"10.1016/j.jtocrr.2024.100703","DOIUrl":"10.1016/j.jtocrr.2024.100703","url":null,"abstract":"<div><h3>Introduction</h3><p>ALK-positive lung cancers represent a molecularly diverse disease. With drug exposure, driving selection pressure, and resistance pathways, disease relapse will emerge. There is compelling rationale to investigate novel treatment strategies, informed by dynamic circulating tumor DNA (ctDNA) monitoring.</p></div><div><h3>Methods</h3><p>The single-arm, pilot study ALKTERNATE investigated fixed alternating cycles of lorlatinib intercalated with crizotinib in individuals resistant to second-generation ALK inhibitors. Dynamic ctDNA explored the correlation with disease response and disease recurrence and defined disease resistance. The primary outcome was time-to-treatment failure, a composite of tolerability, feasibility, and efficacy. Secondary outcomes included standard survival measures, toxicity, pharmacokinetic analysis, and patient-reported outcomes. Tertiary outcomes were proteogenomic analyses of tissue and plasma.</p></div><div><h3>Results</h3><p>A total of 15 individuals were enrolled; three encountered primary resistance to lorlatinib induction. There were 12 participants who received alternating therapy, and this approach revealed safety, feasibility, and effectiveness. Patient-reported outcomes were maintained or improved on therapy, and toxicity was consistent with previous reports. The pharmacokinetic measures were similar to the single-arm drug experience. Median time-to-treatment failure was 10 months; overall survival was 23 months. ctDNA profiles indicated inferior survival in those with preexistent TP53 mutations and those without clear or cleared ctDNA at trial induction. The study defined a vastly heterogeneous population with an abundance of ALK coexisting with non-ALK resistance variants.</p></div><div><h3>Conclusions</h3><p>ALKTERNATE revealed feasibility with a novel alternating ALK inhibitor strategy in ALK-positive NSCLC. Results support progressing inquiry into this approach and propose a flexible design with drug(s) selected and alternating time frames, informed by real-time plasma profiling. Moving this concept to treatment naive may also optimize impact.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100703"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000730/pdfft?md5=c1c8bdf6e1c23cf14396ae61494671f9&pid=1-s2.0-S2666364324000730-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141716515","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":"Effect of FDG PET-CT for Staging and Radiotherapy Planning – A Comparison of Cohorts From Two Randomized Trials of Thoracic Radiotherapy in Limited-Stage SCLC","authors":"","doi":"10.1016/j.jtocrr.2024.100688","DOIUrl":"10.1016/j.jtocrr.2024.100688","url":null,"abstract":"<div><h3>Introduction</h3><p>¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is recommended for staging and defining target volume in limited-stage SCLC, though the impact on outcomes compared with CT staging and elective nodal irradiation (ENI) is not well documented. We analyzed patients receiving 45 Gy/30 fractions in two randomized trials of thoracic radiotherapy (TRT) in limited-stage SCLC (HAST and THORA trials) to evaluate whether PET-CT for staging and radiotherapy planning reduces radiotoxicity and improves survival.</p></div><div><h3>Methods</h3><p>Patients in HAST were staged with CT of the thorax and upper abdomen and brain magnetic resonance imaging of the brain. Patients in THORA were staged with PET-CT in addition. All patients were to receive four courses of platinum/etoposide chemotherapy and concurrent TRT starting three to four weeks after the first chemotherapy course. In HAST, target volumes included pathological lesions on CT plus ENI of lymph node stations 4–7 (bilateral). In THORA, target volumes were limited to PET-CT-positive lesions (selective nodal irradiation [SNI]).</p></div><div><h3>Results</h3><p>A total of 149 patients were included (PET-CT/SNI: n = 76, CT/ENI: n=73); the median age was 64 years, 56% were women, 85% had PS 0 to 1, and 81% had stage III disease. The PET-CT/SNI group experienced less grade 3-4 esophagitis (18% versus 33%, <em>p</em> = 0.043), less grade &gt;=1 pneumonitis (5% versus 16%, <em>p</em> = 0.028), and less dysphagia after TRT (mean scores on European Organisation for Research and Treatment of Cancer 13-item lung cancer module: 45 versus 72). There was no difference in median overall survival (24 versus 25 mo, <em>p</em> = 0.59) or progression-free survival (11 versus 11 mo, <em>p</em> = 0.23).</p></div><div><h3>Conclusions</h3><p>Using PET-CT for staging and target volume definition of TRT reduces acute radiotoxicity but does not improve overall or progression-free survival in limited-stage SCLC.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100688"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000584/pdfft?md5=bf75f29edc6b92975d18460f22eafb5e&pid=1-s2.0-S2666364324000584-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141047048","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 Brief Report of Lung Cancer Screening Utilization Before, During, and in the Later Stages of the COVID-19 Pandemic in the United States","authors":"Hermine Poghosyan PhD, MPH, FAAN ,&nbsp;Sayantani Sarkar PhD ,&nbsp;Ilana Richman MD, MHS ,&nbsp;Robert H. Pietrzak PhD, MPH ,&nbsp;Lisa Carter-Bawa PhD, MPH, APRN, ANP-C, FAAN ,&nbsp;Mary E. Cooley PhD, RN, FAAN","doi":"10.1016/j.jtocrr.2024.100705","DOIUrl":"10.1016/j.jtocrr.2024.100705","url":null,"abstract":"<div><h3>Introduction</h3><p>Although COVID-19 has affected health care and screening utilization, its impact on lung cancer screening (LCS) uptake remains unclear. Our study investigated LCS utilization and associated predictors among adults eligible for LCS before (2019), during (2020–2021), and at a later stage (2022) of COVID-19.</p></div><div><h3>Methods</h3><p>We used cross-sectional, nationally representative, population-based data from the Behavioral Risk Factor Surveillance System over 4 consecutive years: 2019 (n = 4484; weighted n = 1,559,37), 2020 (n = 1239; weighted n = 200,301), 2021 (n = 1673; weighted n = 668,359), and 2022 (n = 20,804; weighted n = 9,458,907). The outcome was self-reported LCS uptake (0 = did not have LCS in the past 12 mo and 1 = underwent LCS in the past 12 mo). We conducted weighted statistics and multivariable logistic regression.</p></div><div><h3>Results</h3><p>Overall, of 11,886,704 million individuals eligible for LCS, 2,129,900 received LCS in 4 years (2019–2022). National rates of LCS among individuals eligible for screening were 16.3% (95% confidence interval [CI]:14.4–18.5), 19.4% (95% CI:15.3–24.3), 18.3% (95% CI:15.6–21.3), and 18.1% (95% CI:17.1–19.2) in 2019, 2020, 2021, and 2022, respectively. Respondents reporting lung disease and cancer (other than lung cancer) history were more likely to receive LCS across all 4 years. During the pandemic (2020), Hispanic (versus White), and rural (versus urban) residents had lower odds of LCS utilization. In 2022, men had increased odds of reporting LCS use relative to women. No sex differences in LCS use were observed in previous years.</p></div><div><h3>Conclusions</h3><p>Our findings indicate consistently low LCS utilization (&lt;20%) over 4 years. Nationwide efforts to boost LCS awareness and utilization are essential for mitigating the lung cancer burden in the United States.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100705"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000754/pdfft?md5=e7d83c19636d902394cdbac4aa9b92ae&pid=1-s2.0-S2666364324000754-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141712889","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":"Three-Year Overall Survival Outcomes and Correlative Analyses in Patients With NSCLC and High (50%–89%) Versus Very High (≥90%) Programmed Death-Ligand 1 Expression Treated With First-Line Pembrolizumab or Cemiplimab","authors":"","doi":"10.1016/j.jtocrr.2024.100675","DOIUrl":"10.1016/j.jtocrr.2024.100675","url":null,"abstract":"<div><h3>Introduction</h3><div>Responses to first-line programmed cell death protein 1 inhibition vary among patients with metastatic NSCLC and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) greater than or equal to 50%. We previously reported improved clinical outcomes to first-line programmed cell death protein 1 inhibition in patients with metastatic NSCLC with a PD-L1 TPS of greater than or equal to 90% versus 50% to 89% in a pilot study. Here, we report the three-year survival with first-line pembrolizumab and cemiplimab in two large independent cohorts of patients with PD-L1 TPS greater than or equal to 90% versus 50% to 89% and characterize genomic and immunophenotypic differences between these PD-L1 expression groups, which were largely unknown.</div></div><div><h3>Methods</h3><div>We analyzed three-year outcomes of the following two independent cohorts: (1) a multicenter cohort of patients from four academic centers in the United States treated with pembrolizumab and (2) EMPOWER-Lung 1, randomized, phase III trial comparing first-line cemiplimab with chemotherapy. Tumor genomic profiling and multiplexed immunofluorescence were performed to evaluate genomic and immunophenotypic correlates of very high PD-L1 expression.</div></div><div><h3>Results</h3><div>At three years of follow-up, progression-free survival (hazard ratio [HR], 0.69; <em>p</em> &lt; 0.001) and overall survival (HR, 0.70; <em>p</em> &lt; 0.01) to first-line commercial pembrolizumab were significantly improved in patients with a PD-L1 TPS greater than or equal to 90% versus 50% to 89%. In the EMPOWER-Lung 1, patients assigned to the cemiplimab arm with a PD-L1 TPS greater than or equal to 90% also had significant improvements in progression-free survival (HR, 0.53; <em>p</em> &lt; 0.0001) and overall survival (HR, 0.63; <em>p</em> = 0.007) compared with those with a PD-L1 of 50% to 89%. Tumor genomic profiling of 553 NSCLC samples revealed that mutations in <em>STK11</em> and <em>SMARCA4</em> were significantly more frequent in tumors with a PD-L1 TPS of 50% to 89% compared with those with a PD-L1 TPS greater than or equal to 90% (Q &lt; 0.15), whereas <em>BRCA2</em> was enriched in NSCLC samples with a PD-L1 TPS greater than or equal to 90% (Q &lt; 0.15). Multiplexed immunofluorescence on 93 NSCLC samples identified higher intratumoral CD8⁺PD1⁺ T cells (<em>p</em> = 0.02) in tumors with PD-L1 TPS greater than or equal to 90% versus 50% to 89%.</div></div><div><h3>Conclusion</h3><div>Pembrolizumab and cemiplimab were found to have long-term survival benefit and favorable genomic and immunophenotypic profile in patients with advanced NSCLC with PD-L1 TPS greater than or equal to 90% compared with TPS 50% to 89%.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100675"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140786686","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":"Eftilagimod Alpha (a Soluble LAG-3 Protein) Combined With Pembrolizumab in Second-Line Metastatic NSCLC Refractory to Anti–Programmed Cell Death Protein 1/Programmed Death-Ligand 1-Based Therapy: Final Results from a Phase 2 Study","authors":"Matthew G. Krebs MD ,&nbsp;Martin Forster MD, PhD ,&nbsp;Margarita Majem MD, PhD ,&nbsp;Julio Peguero MD ,&nbsp;Wade Iams MD ,&nbsp;Tim Clay MD ,&nbsp;Patricia Roxburgh MD, PhD ,&nbsp;Bernard Doger MD, PhD ,&nbsp;Pawan Bajaj MD ,&nbsp;Andres Barba MD ,&nbsp;Suvini Perera MS ,&nbsp;Christian Mueller MS ,&nbsp;Frédéric Triebel MD, PhD","doi":"10.1016/j.jtocrr.2024.100725","DOIUrl":"10.1016/j.jtocrr.2024.100725","url":null,"abstract":"<div><h3>Introduction</h3><div>Eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, triggers antigen-presenting cell and T-cell (CD4⁺ and CD8⁺) activation and helps overcome resistance to programmed cell death protein 1 or programmed cell death-ligand 1 (PD-(L)1) inhibitors. We assessed efti plus pembrolizumab in second-line anti–PD-(L)1-refractory metastatic patients with NSCLC.</div></div><div><h3>Methods</h3><div>After confirmed progression on anti-PD-(L)1-based first-line therapy, patients received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles and then every 3 weeks for up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary endpoint was the objective response rate by modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapies. Secondary endpoints included disease control rate, progression-free survival, overall survival (OS), and tolerability. Exploratory endpoints included tumor growth kinetics and predefined subgroup analyses. Programmed cell death-ligand 1 tumor proportion score was assessed centrally.</div></div><div><h3>Results</h3><div>Thirty-six patients were enrolled from April 2019 to August 2021 using Simon’s two-stage design. Most patients (81.8%) had low or negative (&lt;50%) PD-(L)1 tumor proportion score. First-line therapy was anti–PD-(L)1-based for all patients, combined with chemotherapy for 66.7%. The confirmed objective response and disease control rates were 8.3% and 33.3%. The median progression-free survival was 2.1 months and the median OS was 9.9 months. Patients exhibiting high PD-(L)1 expression or acquired resistance to PD-(L)1 inhibitors revealed superior response and survival outcomes, and OS was closely correlated with disease control. No treatment-emergent adverse event led to permanent discontinuation of study treatment.</div></div><div><h3>Conclusions</h3><div>Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-(L)1 inhibitors, warranting further investigation. Trial registration number: NCT03625323.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100725"},"PeriodicalIF":3.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other Techniques in NSCLC","authors":"Anne Mc Leer PhD ,&nbsp;Julie Mondet PharmD, PhD ,&nbsp;Nelly Magnat MSc ,&nbsp;Mailys Mersch MSc ,&nbsp;Diane Giovannini MD ,&nbsp;Camille Emprou MD ,&nbsp;Anne-Claire Toffart MD, PhD ,&nbsp;Nathalie Sturm MD, PhD ,&nbsp;Sylvie Lantuéjoul MD, PhD ,&nbsp;David Benito PhD","doi":"10.1016/j.jtocrr.2024.100714","DOIUrl":"10.1016/j.jtocrr.2024.100714","url":null,"abstract":"<div><h3>Introduction</h3><div><em>RET</em> rearrangements occur in 1% to 2% NSCLCs. Since no clinically validated RET antibody is currently available, fluorescence in situ hybridization (FISH) is often used as a screening tool to identify patients likely to benefit from RET-targeted therapy. In this study, we performed a comprehensive review of publications in which <em>RET</em>-rearrangement testing was performed by FISH and compared the methods and results with our data.</div></div><div><h3>Methods</h3><div>The findings of an electronic search for publications using <em>RET</em>-FISH in lung cancer were compared with the results obtained at the Grenoble University Hospital where 784 <em>EGFR</em><em>-</em>, <em>KRAS</em><em>-</em>, <em>ALK</em>-, and <em>ROS1</em>-negative NSCLCs were tested by <em>RET</em> break-apart FISH and confirmed by RNA-sequencing (RNA-seq).</div></div><div><h3>Results</h3><div>Out of the 85 publications using <em>RET</em>-FISH analysis, 52 pertained to patients with lung cancer. The most often used positivity threshold was 15%. Six publications compared <em>RET</em>-FISH with at least one other molecular technique on at least eight samples, and the concordance was variable, from 5.9% to 66.7% for FISH-positive cases. Regarding our data, out of the 784 analyzed samples, 32 (4%) were positive by <em>RET</em>-FISH. The concordance between <em>RET</em>-FISH and RNA-seq in <em>RET</em>-FISH positive samples was 69%.</div></div><div><h3>Conclusions</h3><div>Overall, both existing literature and our data suggest that <em>RET</em>-FISH testing can be used for rapid screening of <em>RET</em> rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm <em>RET</em>-FISH-positive cases is essential for ensuring that only patients likely to benefit from <em>RET</em>-target therapy receive the treatment.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100714"},"PeriodicalIF":3.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined RET and MEK Inhibition as a Treatment for RET Fusion-Positive NSCLC With Acquired BRAF Fusion: A Case Report","authors":"Jacobi B. Hines MD ,&nbsp;Benjamin C. Bowar PharmD ,&nbsp;Margaret Colleton MMS ,&nbsp;Lydia Chelala MD ,&nbsp;Peng Wang MD ,&nbsp;Angad A. Chadha MD ,&nbsp;Jeremy Segal MD ,&nbsp;Christine M. Bestvina MD","doi":"10.1016/j.jtocrr.2024.100724","DOIUrl":"10.1016/j.jtocrr.2024.100724","url":null,"abstract":"<div><div><em>RET</em> fusions are present in 1% to 2% of NSCLCs. Although RET inhibitors like selpercatinib are effective, resistance inevitably develops. We present the case of a 28-year-old female with recurrent NSCLC and a <em>CCDC6::RET</em> fusion treated with selpercatinib. Testing at the time of progression revealed a new <em>SKAP2</em><em>:</em>:BRAF fusion. She was then treated with a combination of selpercatinib and trametinib, which led to a likely partial response, despite the combination demonstrating side effects. This case report details the first known instance of NSCLC with a <em>RET</em> fusion developing resistance by means of a <em>BRAF</em> fusion, treated with combined RET and MEK inhibition.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100724"},"PeriodicalIF":3.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Molecular Features of SCLC With a Clinical RNA Expression Panel","authors":"Hilal Ozakinci MD ,&nbsp;Aileen Y. Alontaga PhD ,&nbsp;Pedro Cano MD ,&nbsp;John M. Koomen PhD ,&nbsp;Bradford A. Perez MD ,&nbsp;Amer A. Beg PhD ,&nbsp;Alberto A. Chiappori MD ,&nbsp;Eric B. Haura MD ,&nbsp;Theresa A. Boyle MD, PhD","doi":"10.1016/j.jtocrr.2024.100723","DOIUrl":"10.1016/j.jtocrr.2024.100723","url":null,"abstract":"<div><h3>Introduction</h3><div>The translation of gene expression profiles of SCLC to clinical testing remains relatively unexplored. In this study, gene expression variations in SCLC were evaluated to identify potential biomarkers.</div></div><div><h3>Methods</h3><div>RNA expression profiling was performed on 44 tumor samples from 35 patients diagnosed with SCLC using the clinically validated RNA Salah Targeted Expression Panel (RNA STEP). RNA sequencing (RNA-Seq) and immunohistochemistry were performed on two different SCLC cohorts, and correlation analyses were performed for the <em>ASCL1</em>, <em>NEUROD1</em>, <em>POU2F3</em>, and <em>YAP1</em> genes and their corresponding proteins. RNA STEP and RNA-Seq results were evaluated for gene expression profiles and heterogeneity between SCLC primary and metastatic sites. RNA STEP gene expression profiles of independent SCLC samples (n = 35) were compared with lung adenocarcinoma (n = 160) and squamous cell carcinoma results (n = 25).</div></div><div><h3>Results</h3><div>The RNA STEP results were highly correlated with RNA-Seq and immunohistochemistry results. The dominant transcription regulator by RNA STEP was <em>ASCL1</em> in 74.2% of the samples, <em>NEUROD1</em> in 20%, and <em>POU2F3</em> in 2.9%. The <em>ASCL1</em>, <em>NEUROD1</em>, and <em>POU2F3</em> gene expression profiles were heterogeneous between primary and metastatic sites. SCLCs displayed markedly high expression for targetable genes <em>DLL3</em>, <em>EZH2</em>, <em>TERT</em>, and <em>RET</em>. SCLCs were found to have relatively colder immune profiles than lung adenocarcinomas and squamous cell carcinomas, characterized by lower expression of <em>HLA</em> genes, immune cell, and immune checkpoint genes, except the <em>LAG3</em> gene.</div></div><div><h3>Conclusions</h3><div>Clinical-grade SCLC RNA expression profiling has value for SCLC subtyping, design of clinical trials, and identification of patients for trials and potential targeted therapy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100723"},"PeriodicalIF":3.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}