JTO Clinical and Research Reports最新文献

{"title":"Lung Cancer in Patients of African Descent: A Transcontinental Review of Epidemiology, Disparities, Outcomes, and Opportunities for Equity in Africa, North America, South America, and the Caribbean","authors":"Elvis Obomanu MD ,&nbsp;Colton Jones MD ,&nbsp;Verna Vanderpuye MD ,&nbsp;Nazik Hammad MD","doi":"10.1016/j.jtocrr.2025.100887","DOIUrl":"10.1016/j.jtocrr.2025.100887","url":null,"abstract":"<div><div>Lung cancer in people of African descent is characterized by transcontinental disparities driven by epidemiologic heterogeneity, systemic inequities, and unequal access to health care. Globally, lung cancer incidence and mortality rates vary; however, underdiagnosis and late-stage presentation in low- and middle-income countries obscure the true prevalence of lung cancer because of limited cancer registries and diagnostic infrastructure. In Africa, most patients with lung cancer present at an advanced stage, primarily because of health illiteracy, misdiagnosis, delayed referrals, and inadequate treatment infrastructure. Although tobacco smoking remains a dominant risk factor worldwide, African populations are disproportionately exposed to environmental and occupational hazards, which substantially elevate their lung cancer risk. In North America, Black people experience disproportionately poor outcomes, including lower rates of lung cancer screening, early diagnosis, surgical intervention, and higher mortality rates compared with their White counterparts. In the Caribbean and South America, Black people continue to face racial infrastructural constraints, racial inequities, and elevated exposure to environmental and occupational carcinogens. Systemic barriers perpetuate these disparities, including limited access to screening, genomic testing, and guideline-concordant therapies.</div><div>Achieving equity in lung cancer outcomes requires strategic initiatives, including the expansion of lung cancer registries in Africa, the Caribbean, and South America, to inform evidence-based interventions. Urgent national and international measures focused on prevention and care for populations of African descent, implementing robust tobacco control policies, addressing systemic and racial inequities, and strengthening health care systems to report and manage lung cancer efficiently are essential steps toward reducing disparities. A transcontinental collaborative approach that includes establishing lung cancer research consortia is vital to share best practices in screening protocols, optimize early detection strategies and treatment, and advocate for policy reforms that address the global burden of lung cancer in populations of African descent.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100887"},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete Response to BET Inhibitor in Primary Pulmonary NUT Carcinoma With Single-Cell Sequencing-Based Analysis: A Case Report","authors":"Zhuomiao Ye MD ,&nbsp;Xin Li PhD ,&nbsp;Minghui Zhang PhD ,&nbsp;Fei Xie MD ,&nbsp;Xiangwen Luo MSc ,&nbsp;Chao Deng MD ,&nbsp;Dan Yang MSc ,&nbsp;Mingzhu Yin PhD","doi":"10.1016/j.jtocrr.2025.100885","DOIUrl":"10.1016/j.jtocrr.2025.100885","url":null,"abstract":"<div><div>NUT carcinoma is a rare and highly aggressive malignancy characterized by rapid progression, resistance to conventional therapies, and an extremely poor prognosis. This report presents a 36-year-old patient with stage IIIB primary pulmonary NUT carcinoma who achieved remarkable clinical outcomes with NHWD-870 monotherapy, a novel BET inhibitor. After just 1 month of treatment, imaging revealed a partial response, and a complete response was achieved within 5 months. Postoperative pathologic examination confirmed no residual cancer cells, and the patient has remained disease-free without recurrence or metastasis to date. To explore the underlying mechanisms of this therapeutic response, single-cell RNA sequencing was performed on the tumor tissue, revealing enhanced activity of immune cells, particularly effector CD8+ T-cells, within the tumor microenvironment. This suggests that NHWD-870 exerts its effects through both direct tumor suppression and modulation of the immune microenvironment. This case highlights the exceptional efficacy of BET inhibitors in the treatment of NUT carcinoma, as evidenced by the first report of complete response achieved with BET inhibitor monotherapy, and supports their potential as a personalized therapeutic strategy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100885"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durvalumab With or Without Tremelimumab in Combination With Chemoradiotherapy in Patients With Limited-Stage SCLC: Results from the Phase 1 CLOVER Study","authors":"Byoung Chul Cho MD, PhD ,&nbsp;Myung-Ju Ahn MD ,&nbsp;Makoto Nishio MD ,&nbsp;Haruyasu Murakami MD ,&nbsp;Dong Wan-Kim MD ,&nbsp;Sang-We Kim MD ,&nbsp;Sana D. Karam MD ,&nbsp;Ana Estival PhD ,&nbsp;Chia-Chi Lin MD, PhD ,&nbsp;Jose Manuel Trigo MD ,&nbsp;Rosa Alvarez MD ,&nbsp;Chih Liang Wang MD ,&nbsp;Mingchao Xie PhD ,&nbsp;Sonia Iyer PhD ,&nbsp;Jon Armstrong MSc ,&nbsp;Priti Chugh PhD ,&nbsp;Haiyi Jiang MD ,&nbsp;Julie E. Bauman MD","doi":"10.1016/j.jtocrr.2025.100884","DOIUrl":"10.1016/j.jtocrr.2025.100884","url":null,"abstract":"<div><h3>Introduction</h3><div>The phase 1 CLOVER study (NCT03509012) evaluated durvalumab with or without tremelimumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; here, we report findings from the limited-stage SCLC (LS-SCLC) cohort.</div></div><div><h3>Methods</h3><div>Patients with pathologically confirmed LS-SCLC whose disease could be encompassed within a radical radiation portal received durvalumab (arms 1 and 2) or durvalumab plus tremelimumab (arms 3 and 4) in combination with cCRT (cisplatin-etoposide and either standard radiotherapy [arms 1 and 3] or hyperfractionated radiotherapy [arms 2 and 4]). The primary end point was safety and tolerability. Preliminary efficacy and candidate biomarkers of response were assessed.</div></div><div><h3>Results</h3><div>Overall, 33 patients were enrolled: 12 in arm 1, 12 in arm 2, six in arm 3, and three in arm 4. No patients had dose-limiting toxicity. Grade 3 or 4 adverse events occurred in 79.2% of patients from arms 1 and 2 and 88.9% from arms 3 and 4; the most common were hematologic events. In arms 1, 2, 3, and 4, objective response rate was 66.7%, 66.7%, 83.3%, and 100.0%, disease control rate was 90.9%, 100.0%, 100.0%, and 100.0% at 18 weeks and 72.7%, 83.3%, 100.0%, and 100.0% at 48 weeks, and the median progression-free survival (PFS) (95% confidence interval) was 9.2 months (5.3‒not estimable [NE]), 16.6 months (8.4–NE), not reached (16.6–NE), and 9.3 months (6.3–NE), respectively. In exploratory biomarker analyses, no difference in PFS by programmed cell death-ligand 1 expression level was observed; median PFS was numerically greater in high versus low tumor inflammation signature and <em>CD8A</em> expression subgroups.</div></div><div><h3>Conclusions</h3><div>Durvalumab in combination with cCRT, with or without tremelimumab, was tolerable and active in patients with LS-SCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100884"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis Exploring Tyrosine Kinase Inhibitor-Induced Weight Gain in Oncogene-Addicted NSCLC","authors":"Ilaria Mariangela Scaglione MD ,&nbsp;Alice Avancini PhD ,&nbsp;Serena Eccher MD ,&nbsp;Anita Borsati MSc ,&nbsp;Luca Pasqualin MD ,&nbsp;Giulia La Cava MD ,&nbsp;Ilaria Trestini RD ,&nbsp;Daniela Tregnago PhD ,&nbsp;Marco Sposito MD ,&nbsp;Jessica Insolda MSc ,&nbsp;Diana Giannarelli PhD ,&nbsp;Michele Milella MD ,&nbsp;Sara Pilotto PhD ,&nbsp;Lorenzo Belluomini PhD","doi":"10.1016/j.jtocrr.2025.100881","DOIUrl":"10.1016/j.jtocrr.2025.100881","url":null,"abstract":"<div><h3>Background</h3><div>For patients with oncogene-addicted NSCLC treated with tyrosine kinase inhibitors (TKIs), weight gain has recently gained attention as a frequent treatment-related effect. Identifying those TKIs more frequently associated with weight gain is crucial for further characterizing body composition-related modifications, deepening their metabolic impact, and guiding treatment decisions, considering the potential influence of weight gain on patients' quality of life and long-term outcomes.</div></div><div><h3>Methods</h3><div>A systematic search was conducted across PubMed, Scopus, Cochrane, and meeting resources. A meta-analysis was conducted to quantify the magnitude of weight gain, and meta-regression was applied to explore the association between this side effect, and demographic and clinical parameters.</div></div><div><h3>Results</h3><div>Among 7596 identified studies from January 2009 to December 2024, 18 pivotal trials reporting weight gain data were included in the final analysis, encompassing a total of 25 arms. Lorlatinib revealed the highest risk of treatment-induced weight gain [incidence 36%; 95% confidence interval (CI): 26%–46%; I² = 92%], followed by alectinib [incidence 15%; 95% CI: 12%–18%; I² = 52%] and crizotinib [incidence 5%; 95% CI: 0%–13%; I² = 93%]. Osimertinib and erlotinib indicated the lowest incidence of weight gain. The meta-regression revealed no significant correlation among weight gain, sex, age, and performance status, thus suggesting a drug-specific effect.</div></div><div><h3>Conclusions</h3><div>Our findings confirmed the unique profile of lorlatinib regarding weight gain, regardless of patient characteristics. Considering the impressive prognostic horizons achievable with TKIs in oncogene-addicted NSCLC, adequate reporting in clinical trials, assessment and monitoring of weight gain, body composition modifications, and impact on quality of life should be prioritized, together with adequate lifestyle-based strategies for its management.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100881"},"PeriodicalIF":3.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monotherapy With Immune Checkpoint Blockade Improves Survival Outcomes in KRAS-Mutant but Not KRAS Wild-Type Metastatic Lung Adenocarcinoma: Validation From an Extended Swedish Cohort","authors":"Ella A. Eklund MD ,&nbsp;Sama I. Sayin MD, PhD ,&nbsp;Jonas Smith Jonsson MD ,&nbsp;Hannes van Renswoude MD ,&nbsp;Jan Nyman MD, PhD ,&nbsp;Andreas Hallqvist MD, PhD ,&nbsp;Clotilde Wiel PhD ,&nbsp;Volkan I. Sayin PhD","doi":"10.1016/j.jtocrr.2025.100880","DOIUrl":"10.1016/j.jtocrr.2025.100880","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Immune checkpoint blockade (ICB) is a standard first-line treatment for stage IV NSCLC without actionable oncogenic alterations. &lt;em&gt;KRAS&lt;/em&gt; mutations, prevalent in 30% to 40% lung adenocarcinomas (LUAD) in Western populations, currently lack targeted first-line therapies. This study aimed to assess the predictive value of &lt;em&gt;KRAS&lt;/em&gt; mutations for clinical outcomes after distinct ICB regimens, validating our previous findings in a larger cohort with extended follow-up.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a retrospective multicenter study including consecutive stage IV LUAD patients (n = 424) treated with either ICB or platinum-doublet chemotherapy between 2016 and 2021 in Western Sweden. Patient demographics, tumor characteristics, treatment details, and survival outcomes were retrospectively collected from patient charts and the Swedish National Lung Cancer Registry. &lt;em&gt;KRAS&lt;/em&gt; mutational status was assessed by next-generation sequencing. Primary end points included overall survival (OS) and progression-free survival (PFS), analyzed using Kaplan-Meier curves and multivariate Cox regression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among 424 patients diagnosed with metastatic LUAD, 40% harbored &lt;em&gt;KRAS&lt;/em&gt; mutations (&lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;MUT&lt;/sup&gt;). &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;MUT&lt;/sup&gt; patients exhibited significant improvement in OS (16 versus 8 mo, &lt;em&gt;p&lt;/em&gt; &lt; 0.001) and PFS (8 mo versus 5 mo, &lt;em&gt;p&lt;/em&gt; &lt; 0.001) with ICB monotherapy. In contrast, &lt;em&gt;KRAS&lt;/em&gt; wild-type (&lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;WT&lt;/sup&gt;) patients derived no survival advantage from ICB monotherapy (OS, 8 mo versus 8 mo, &lt;em&gt;p&lt;/em&gt; = 0.648; PFS 4 mo versus 5 mo, &lt;em&gt;p&lt;/em&gt; = 0.871) although they did so with chemoimmunotherapy (OS, 15 mo versus 8 mo, &lt;em&gt;p&lt;/em&gt; = 0.032; PFS, 6 mo vs 5 mo, &lt;em&gt;p&lt;/em&gt; = 0.033). On multivariate analysis, monotherapy was confirmed as an independent factor improving outcomes in KRAS-mutated patients (hazard ratio [HR] 0.533, 95% confidence interval 0.311-0.912, &lt;em&gt;p&lt;/em&gt; = 0.018). Finally, we identified &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12C&lt;/sup&gt; (OS: 13.7 mo versus 10.5 mo, &lt;em&gt;p&lt;/em&gt; = 0.0046, PFS: 7.7 mo versus 6.2 mo, &lt;em&gt;p&lt;/em&gt; = 0.002) and &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12V&lt;/sup&gt; (OS: 24.2 mo versus 7.2 mo, &lt;em&gt;p&lt;/em&gt; = 0.0204; PFS: 13.7 mo versus 4.5 mo, &lt;em&gt;p&lt;/em&gt; = 0.063) but not &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12D&lt;/sup&gt; (OS, 5.8 mo versus 6.2 mo, &lt;em&gt;p&lt;/em&gt; = 0.777; PFS, 4.6 mo versus 3.2 mo, &lt;em&gt;p&lt;/em&gt; = 0.694) as distinctly and independently predictive of improved survival after receiving ICB-containing treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;&lt;em&gt;KRAS&lt;/em&gt; mutations predict substantial and sustained clinical benefit from first-line ICB monotherapy in metastatic LUAD, whereas &lt;em&gt;KRAS&lt;/em&gt; wild-type patients do not. &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12C&lt;/sup&gt; and &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12V&lt;/sup&gt; mutations confer improved survival, whereas &lt;em&gt;KRAS&lt;/em&gt;&lt;sup&gt;G12D&lt;/sup&gt; does not. Integrating &lt;em&gt;KRAS&lt;/em&gt; mutation status into clinical practice could","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100880"},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: Prospective Trial of Pembrolizumab Monotherapy in Metastatic NSCLC Evaluating Circulating Tumor DNA as a Surrogate Biomarker of Response","authors":"Iris van 't Erve PhD ,&nbsp;Isabelle Blanchard BS ,&nbsp;Judy Y. Pagtama MSN ,&nbsp;Alison J. Holmes Tisch MSN ,&nbsp;Ash A. Alizadeh MD, PhD ,&nbsp;Kavitha Ramchandran MD ,&nbsp;Heather A. Wakelee MD ,&nbsp;Sukhmani K. Padda MD ,&nbsp;Maximilian Diehn MD, PhD ,&nbsp;Joel W. Neal MD, PhD","doi":"10.1016/j.jtocrr.2025.100877","DOIUrl":"10.1016/j.jtocrr.2025.100877","url":null,"abstract":"<div><div>Immune checkpoint inhibitors provide clinical benefit to a subset of patients with metastatic NSCLC, yet the reliable prediction of long-term outcomes remains challenging. We conducted a prospective phase 2 clinical trial to evaluate circulating tumor DNA (ctDNA) as a surrogate biomarker for early clinical response to pembrolizumab monotherapy (NCT02955758). Tumor-informed targeted sequencing of pretreatment and early on-treatment plasma ctDNA in 25 patients with metastatic NSCLC was performed. On-treatment ctDNA response, defined as at least a threefold ctDNA variant allele frequency decrease after three cycles of pembrolizumab versus baseline, was able to predict with 100%, 66%, and 100% accuracy partial response, stable disease, and progressive disease radiologic response, respectively. Molecular response was also correlated with progression-free survival. This study confirms the potential clinical utility of early on-treatment ctDNA-based response evaluation in patients treated with immune checkpoint inhibitors, creating the opportunity for early treatment intervention in nonresponders.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100877"},"PeriodicalIF":3.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Older Adult Participation in Early-Phase Lung Cancer Clinical Trials, 1998 to 2020","authors":"Desirae Ehley MD ,&nbsp;Lilit Vardanyan MS ,&nbsp;Rebecca S. Boxer MD, MS ,&nbsp;Alex J. Fauer PhD ,&nbsp;Shiruyeh Schokrpur MD, PhD ,&nbsp;David Gandara MD ,&nbsp;Jonathan W. Riess MD, MAS ,&nbsp;Surbhi Singhal MD","doi":"10.1016/j.jtocrr.2025.100873","DOIUrl":"10.1016/j.jtocrr.2025.100873","url":null,"abstract":"<div><h3>Objectives</h3><div>Despite advances, lung cancer treatment remains associated with substantial toxicity. Early-phase clinical trials inform the safety and efficacy of novel lung cancer treatments. Although older adults represent most patients with lung cancer, and they are underrepresented in phase 3 trials, age disparity in early-phase lung cancer trials is ill-defined.</div></div><div><h3>Methods</h3><div>We queried <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> to identify early-phase interventional clinical trials conducted in adults with lung cancer since database conception. We calculated the difference in age (DA) between the clinical trial populations and U.S. populations, using <em>t</em> test and one-sided analysis of variance to evaluate trial characteristics associated with DA.</div></div><div><h3>Results</h3><div>We identified 141 clinical trials enrolling 7723 participants from 1998 to 2020. Early-phase lung cancer trial participants were, on average, 7.6 years younger than patients with lung cancer in the U.S. population (mean DA: −7.6 y, SD 4.2). Age disparities were magnified among clinical trials that were industry-sponsored (mean DA −8.5 versus −6.1, <em>p</em> = 0.001) and those limiting eligibility to Eastern Cooperative Oncology Group performance status less than or equal to 1 (mean DA –8.0 versus −6.0, <em>p</em> = 0.040). There was no association between the median age of trial participants and the proportion of patients with serious adverse events.</div></div><div><h3>Conclusions</h3><div>Older adults remain underrepresented in early-phase lung cancer clinical trials. With the rapid expansion of novel cancer therapies, focused efforts in the design of early-phase trials are warranted to reflect real-world populations. Otherwise, limitations in the generalizability of treatment safety and efficacy may increase in the future.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100873"},"PeriodicalIF":3.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Weight Gain as a Risk Factor for Increased Maximum Weight Gain Among Patients With NSCLC on Lorlatinib and Other ALK Tyrosine Kinase Inhibitors","authors":"Alexander S. Watson MD, DPhil ,&nbsp;Alyse W. Staley MS ,&nbsp;Benjamin Yoder PharmD, BCOP ,&nbsp;Sean J. Iwamoto MD ,&nbsp;Vida Alami BA ,&nbsp;Erin L. Schenk MD, PhD ,&nbsp;Tejas Patil MD ,&nbsp;D. Ross Camidge MD, PhD ,&nbsp;John M. Taormina MD","doi":"10.1016/j.jtocrr.2025.100870","DOIUrl":"10.1016/j.jtocrr.2025.100870","url":null,"abstract":"<div><h3>Introduction</h3><div>Therapy-associated weight gain affects the quality of life and health of patients with ALK-positive NSCLC treated with tyrosine kinase inhibitors (TKIs). The severity and timing of real-world weight gain on ALK TKIs and associated risk factors are poorly understood, impairing timely interventions.</div></div><div><h3>Methods</h3><div>A retrospective chart review of patients with ALK-positive NSCLC receiving TKIs at our institution from January 1, 2020 to December 31, 2023 was conducted. Demographics, metabolic comorbidities, treatment details, and clinic-measured weights were collected. The grade of weight gain, maximum weight gain (% of baseline), and early weight gain (within 6 mo of TKI start) were calculated. Univariable and multivariable linear mixed effects analyses for predictors of weight gain were performed.</div></div><div><h3>Results</h3><div>A total of 91 patients received 156 treatment lines of TKI. Patients receiving lorlatinib experienced significantly higher maximum weight gain (mean 13.5% [95% confidence interval 10.8–16.2]) than those receiving other TKIs (<em>p</em> &lt;0.001). Any-grade and grade 3 weight gain rates exceeded those from clinical trials. In multivariate modeling, early weight gain of at least 5% within 6 months (<em>p</em> &lt;0.001), lorlatinib use (<em>p</em> = 0.007), and age 50 years or younger (<em>p</em> = 0.046) were associated with maximum weight gain. Among patients receiving lorlatinib, early weight gain (<em>p</em> = 0.001) remained significantly associated with higher maximum weight gain.</div></div><div><h3>Conclusions</h3><div>In this real-world cohort, rates and severity of weight gain on ALK TKIs were higher than in registrational trials, and highest on lorlatinib. Patients with early weight gain of greater than or equal to 5% within 6 months developed higher maximum gain. Prospective investigation of early weight management interventions is encouraged.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100870"},"PeriodicalIF":3.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?","authors":"Sun Min Lim MD, PhD ,&nbsp;Joo Sung Gabriel Shim MD ,&nbsp;Hyo Sup Shim MD, PhD ,&nbsp;Junko Tanizaki MD, PhD ,&nbsp;Jorn Nutzinger MD ,&nbsp;Byoung Chul Cho MD, PhD ,&nbsp;Ross A. Soo MBBS, PhD","doi":"10.1016/j.jtocrr.2025.100871","DOIUrl":"10.1016/j.jtocrr.2025.100871","url":null,"abstract":"<div><div>SCLC is a high-grade neuroendocrine malignancy associated with poor prognosis, comprising 15% of lung cancer cases globally. Advances in genetic profiling have revealed that SCLC is a molecularly heterogeneous disease, categorized into subtypes such as SCLC-A, SCLC-N, SCLC-P, and SCLC-I, on the basis of their neuroendocrine and immune-related characteristics. This heterogeneity underscores the need for tailored therapeutic strategies.</div><div>Large cell neuroendocrine carcinoma (LCNEC) shares histologic and molecular similarities with SCLC but remains a distinct entity. LCNEC is categorized into two major subtypes: Type I, characterized by <em>STK11</em> and <em>KEAP1</em> mutations and a neuroendocrine phenotype, and Type II, defined by <em>TP53</em> and <em>RB1</em> alterations with higher proliferative indices. LCNEC's rarity and molecular diversity present challenges for standardized treatment, further highlighting the need for comparative research with SCLC.</div><div>In this review, we highlight the genetic and clinicopathologic features of SCLC and LCNEC. Furthermore, we discuss emerging therapeutics and future directions in the treatment of SCLC and LCNEC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100871"},"PeriodicalIF":3.5,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-line Selpercatinib or Chemotherapy and Pembrolizumab in Patients From East Asia With RET Fusion–Positive NSCLC: A LIBRETTO-431 Subgroup Analysis","authors":"Koichi Goto MD, PhD ,&nbsp;Herbert H. Loong M.B.B.S. ,&nbsp;Caicun Zhou MD, PhD ,&nbsp;Kazumi Nishino MD, PhD ,&nbsp;Dae Ho Lee MD, PhD ,&nbsp;Se-Hoon Lee MD ,&nbsp;James Chih-Hsin Yang MD, PhD ,&nbsp;Dan Liu PhD ,&nbsp;Minji Kim Uh PhD ,&nbsp;Hongmei Han MS, MAS ,&nbsp;Tarun Puri MD ,&nbsp;Aimee Bence Lin PhD ,&nbsp;Ying Cheng MD","doi":"10.1016/j.jtocrr.2025.100868","DOIUrl":"10.1016/j.jtocrr.2025.100868","url":null,"abstract":"<div><h3>Introduction</h3><div>Selpercatinib’s consistent efficacy and manageable safety profile were observed in patients with <em>RET</em> fusion–positive NSCLC across geographies in single-arm studies (LIBRETTO-001 and LIBRETTO-321). Here, we report the efficacy and safety of the phase 3 study LIBRETTO-431 in patients from East Asia.</div></div><div><h3>Methods</h3><div>LIBRETTO-431 (NCT04194944) is a randomized, open-label phase 3 trial comparing first-line selpercatinib versus pemetrexed and platinum with or without pembrolizumab. Geography (East Asia versus non-East Asia) was a stratification factor. Efficacy end points including progression-free survival (PFS), objective response rate, and duration of response as assessed by means of blinded independent central review were evaluated in patients from East Asia. Pharmacokinetics were assessed in the selpercatinib group. Safety data were collected for all patients who received at least one dose of study treatment.</div></div><div><h3>Results</h3><div>Of the 261 patients enrolled, 142 (54.4%) were from East Asia, with 116 randomized to the intention-to-treat-pembrolizumab population (selpercatinib: n = 75, control: n = 41). With a median follow-up of 19.4 and 21.2 months in the selpercatinib and control groups respectively, the median PFS in patients from East Asia was not yet reached for selpercatinib (95% confidence interval (CI): 16.4–not evaluable) versus 11.1 months (95% CI: 7.0–16.8) for control (hazard ratio: 0.38 [95%CI: 0.22–0.68]; <em>p</em> = 0.0008). Safety and pharmacokinetics were consistent with those previously reported across the development program and adverse events were generally manageable with dose adjustments.</div></div><div><h3>Conclusions</h3><div>Consistent with results in the overall LIBRETTO-431 population, selpercatinib exhibited superior PFS compared with chemotherapy plus pembrolizumab in patients from East Asia with a manageable safety profile. These data further highlight the importance of early comprehensive genomic testing and the use of selpercatinib as a preferred first-line regimen in patients with <em>RET</em> fusion–positive NSCLC across geographies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100868"},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}