JTO Clinical and Research Reports最新文献

{"title":"Treatment Patterns, Outcome, and Quality of Life of Patients With Extensive-Stage SCLC Receiving Third-Line Therapy—Data From the German CRISP Registry (AIO-TRK-0315): A Brief Report","authors":"Maximilian Rost MD ,&nbsp;Rieke Fischer MD ,&nbsp;Martin Reck MD, PhD ,&nbsp;Thomas Gauler MD, PhD ,&nbsp;Cornelius Waller MD, PhD ,&nbsp;Petros Christopoulos MD, PhD ,&nbsp;Petra Hoffknecht MD ,&nbsp;Martina Jänicke PhD ,&nbsp;Annette Fleitz PhD ,&nbsp;Andrea Härzschel PhD ,&nbsp;Carolin Lennartz PhD ,&nbsp;Paula Ludwig MSc ,&nbsp;Annika Groth MD, PhD ,&nbsp;Michael Bendel MD ,&nbsp;Jan Stratmann MD, PhD ,&nbsp;Frank Griesinger MD, PhD ,&nbsp;Michael Thomas MD, PhD ,&nbsp;Wilfried E.E. Eberhardt MD, PhD ,&nbsp;Martin Sebastian MD ,&nbsp;CRISP Registry Group","doi":"10.1016/j.jtocrr.2026.100959","DOIUrl":"10.1016/j.jtocrr.2026.100959","url":null,"abstract":"<div><h3>Introduction</h3><div>Recurrent extensive-stage SCLC (ES-SCLC) remains a major therapeutic challenge. Although immune checkpoint inhibitors (2Ls), bispecific antibodies, and antibody-drug conjugates offer promise in early lines, outcomes beyond the second line (2L) remain poor. Real-world data on third line (3L) treatment patterns, clinical outcomes, and quality of life (QoL) after ICI-based first line (1L) therapy are limited but critical to inform clinical decision-making.</div></div><div><h3>Methods</h3><div>CRISP is a prospective, multicenter registry for patients with lung cancer in Germany. In-depth patient and tumor characteristics, details about treatments, outcome, and patient-reported outcomes data are collected. Between September 2019 and April 2021, 114 sites in Germany recruited 518 patients with ES-SCLC, of which 82 started 3L therapy.</div></div><div><h3>Results</h3><div>Of 82 patients, 58.5% were male and 79.3% were below 70 years old. At 3L start, Eastern Cooperative Oncology Group performance score was 0 in 18.3%, 1 in 39.0%, and more than or equal to 2 in 19.5% (23.2% unknown). In the 1L setting, 68 patients (82.9%) received platinum-based chemotherapy plus ICI and 68 (82.9%) were platinum refractory (time to next treatment &lt; 3 mo). Furthermore, 2L therapy consisted of topotecan (47.6%) and other chemotherapies (52.4%). The three most common 3L regimens were paclitaxel (22%), topotecan (22%), and cyclophosphamide, doxorubicin, vincristine (17.1%). Local radiotherapy was used in 19 patients (23.2%) in the 3L. Median real-world progression-free survival was 2.2 months (95% confidence interval: [1.8–3.0]), and real-world overall survival was 4.4 months (95% confidence interval: [3.4–5.2]). Exploratory analyses revealed numerically longer real-world overall survival with increasing time between 1L and 2L initiation (&lt;6 mo: 3.4 mo; 6–11 mo: 4.4 mo; ≥ 12 mo: 8.3 mo) and in patients with Eastern Cooperative Oncology Group performance score 0 to 1 versus more than or equal to 2 (5.1 versus 4.4 mo). QoL, assessed by FACT-L subscales, remained stable during follow-up.</div></div><div><h3>Conclusions</h3><div>Outcomes in 3L therapy in ES-SCLC remain poor among subgroups, even in predominantly ICI-pretreated patients, strongly highlighting the need for better 3L strategies. Although QoL can be preserved, therapeutic efficacy is lacking. These real-world data are critical to support shared decision-making, helping clinicians and patients weigh the limited benefits of further chemotherapy against best supportive care.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100959"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147601450","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":"Long-Term Response and Survival in Extensive-Stage SCLC Receiving Atezolizumab Plus Chemotherapy in a Real-World Setting: IFCT-1905 CLINATEZO","authors":"Lionel Falchero MD ,&nbsp;Karim Amrane MD ,&nbsp;Benoît Godbert MD ,&nbsp;Bénédicte Leterre MD ,&nbsp;Jeannick Madelaine MD ,&nbsp;Pierre Fournel MD, PhD ,&nbsp;Céline Mascaux MD, PhD ,&nbsp;Judith Raimbourg MD ,&nbsp;Sophie Schneider MD ,&nbsp;Aurélie Swalduz MD ,&nbsp;Rémi Veillon MD ,&nbsp;Alexandra Langlais MSc ,&nbsp;Pascale Missy PhD ,&nbsp;Franck Morin MSc ,&nbsp;Virginie Westeel MD, PhD ,&nbsp;Nicolas Girard MD, PhD","doi":"10.1016/j.jtocrr.2026.100964","DOIUrl":"10.1016/j.jtocrr.2026.100964","url":null,"abstract":"<div><h3>Introduction</h3><div>Extensive-stage SCLC (ES-SCLC) is a highly aggressive type of lung cancer with a high risk of early progression and limited survival. Standard of care for first-line treatment is platinum-etoposide chemotherapy plus anti–PD-L1 immune checkpoint inhibitors.</div></div><div><h3>Methods</h3><div>Intergroupe Francophone de Cancérologie Thoracique-1905 CLINATEZO is a nationwide, non-interventional, retrospective study of consecutive patients with ES-SCLC who received atezolizumab plus platinum-based chemotherapy as part of the French Early Access Program that ran from May 2019 to March 2020. In this analysis, predictors of long-term response (defined by a real-world progression-free survival [rwPFS] &gt; 12 mo) and long-term survival (defined by an overall survival [OS] &gt; 24 mo) were assessed.</div></div><div><h3>Results</h3><div>A total of 517 patients were enrolled from 65 centers. After a median follow-up of 53.8 months, median, 12-month, and 48-month rwPFS rates were 5.2 (95% confidence interval [CI]: 5.0–5.4) months, 14.6% (95% CI: 11.6–17.9), and 6.8% (95% CI: 4.7–9.4), respectively. Median, 24-month, and 48-month OS rates were 11.3 (95% CI: 10.1–12.4) months, 21.1% (95% CI: 17.7–24.8), and 11.4% (95% CI: 8.8–14.4), respectively.</div><div>Long-term response was observed in 12.6% patients. Median OS was 9.7 months in patients with rwPFS less than or equal to 12 months and 53.7 months in patients with rwPFS more than 12 months. Baseline characteristics associated with rwPFS more than 12 months were being a former smoker (versus current smoker, <em>p</em> = 0.003) and having an Eastern Cooperative Oncology Group performance status of 0 to 1 (versus 2, <em>p</em> = 0.048).</div><div>Long-term survival was observed in 20.5% patients. Median OS was 8.8 months in patients with OS less than or equal to 24 months and 52.9 months in patients with OS more than 24 months. Predictors of long-term survival were younger age (<em>p</em> = 0.030), limited stage at initial diagnosis of SCLC (<em>p</em> = 0.022), and previous line of platinum-based chemotherapy (<em>p</em> = 0.01).</div></div><div><h3>Conclusions</h3><div>CLINATEZO demonstrates the reproducibility of the key survival outcomes of landmark trials, in a real-life setting, for patients with ES-SCLC. Only low smoking history and performance status were associated with long-term response in our cohort.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100964"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147601358","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":"Efficacy of Adding Immune Checkpoint Inhibition to Chemotherapy, With or Without VEGF Inhibition, in Patients With Advanced EGFR-Mutated NSCLC: A Systematic Review and Meta-Analysis With Reconstructed Individual Patient Data","authors":"Alessandro Di Federico MD ,&nbsp;Sara Stumpo MD ,&nbsp;Linda Danielli MD ,&nbsp;Giacomo Corradi MD ,&nbsp;Biagio Ricciuti MD, PhD ,&nbsp;Federica Pecci MD ,&nbsp;Joao V. Alessi MD ,&nbsp;Xinan Wang PhD ,&nbsp;Andrea De Giglio MD, PhD ,&nbsp;Francesca Lo Bianco MD ,&nbsp;Francesco Mantuano MD ,&nbsp;Maria A. Pantaleo PhD ,&nbsp;Francesca Sperandi MD ,&nbsp;Barbara Melotti MD ,&nbsp;Francesco Gelsomino MD, PhD ,&nbsp;Andrea Ardizzoni MD","doi":"10.1016/j.jtocrr.2026.100961","DOIUrl":"10.1016/j.jtocrr.2026.100961","url":null,"abstract":"<div><h3>Introduction</h3><div>Whether adding immunotherapy to chemotherapy is beneficial for some patients with <em>EGFR</em>-mutated NSCLC and whether concomitant vascular endothelial growth factor inhibition (VEGFi) further enhances this strategy are still subjects of debate.</div></div><div><h3>Methods</h3><div>We performed a systematic review and meta-analysis with reconstructed individual patient data to assess outcomes to chemo-immunotherapy with or without VEGFi in patients with advanced <em>EGFR</em>-mutated NSCLC after failure of EGFR tyrosine kinase inhibitors.</div></div><div><h3>Results</h3><div>Among seven randomized clinical trials (n = 2196 patients), compared with chemotherapy with or without VEGFi, chemo-immunotherapy extended the median progression-free survival whether combined with VEGFi (8.1 versus 5.5 mo; hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.53–0.67; <em>p</em> &lt; 0.0001) or not (5.6 versus 5.5 mo; HR: 0.83; 95% CI: 0.74–0.93; <em>p</em> = 0.0017). Adding VEGFi to chemo-immunotherapy prolonged the progression-free survival even compared with chemo-immunotherapy alone (HR: 0.72; 95% CI: 0.63–0.82; <em>p</em> &lt; 0.0001). Similarly, median overall survival was extended by chemo-immunotherapy with VEGFi (19.0 versus 15.7 mo; HR: 0.77; 95% CI: 0.67–0.89; <em>p</em> = 0.00046) and without VEGFi (18.1 versus 15.7 mo; HR: 0.86; 95% CI: 0.76–0.97; <em>p</em> = 0.018) compared with chemotherapy with or without VEGFi. However, adding VEGFi to chemo-immunotherapy did not extend the median overall survival compared with chemo-immunotherapy alone (HR: 0.90; 95% CI: 0.77–1.05; <em>p</em> = 0.18). These results were consistent in trial-level HR meta-analyses, where chemo-immunotherapy, only when combined with VEGFi, also improved the objective response rate versus chemotherapy with or without VEGFi. Patients with PD-L1 more than or equal to 1% or L858R mutations achieved greater PFS benefit with chemo-immunotherapy with or without VEGFi.</div></div><div><h3>Conclusion</h3><div>Chemo-immunotherapy with or without VEGFi may produce a modest survival improvement in select patients with <em>EGFR</em>-mutated NSCLC compared with chemotherapy. Identifying biomarkers able to predict a clinically meaningful benefit is warranted.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100961"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147601497","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":"Clinical Outcomes and Safety of Concurrent Chemoradiotherapy in EGFR-Mutant Unresectable Stage III NSCLC","authors":"Shinkichi Takamori MD, PhD ,&nbsp;Toshio Shimokawa PhD ,&nbsp;Atsushi Osoegawa MD, PhD ,&nbsp;Miyuki Abe MD, PhD ,&nbsp;Yohei Takumi MD, PhD ,&nbsp;Shunichi Sugawara MD, PhD ,&nbsp;Seiji Niho MD, PhD ,&nbsp;Yasushi Goto MD, PhD ,&nbsp;Hiroaki Okamoto MD, PhD ,&nbsp;Katsuyuki Hotta MD, PhD ,&nbsp;Yuichi Ozawa MD, PhD ,&nbsp;Satoshi Oizumi MD, PhD ,&nbsp;Nobuyuki Yamamoto MD, PhD ,&nbsp;Tetsuya Mitsudomi MD, PhD ,&nbsp;Masafumi Yamaguchi MD, PhD","doi":"10.1016/j.jtocrr.2025.100897","DOIUrl":"10.1016/j.jtocrr.2025.100897","url":null,"abstract":"<div><h3>Introduction</h3><div>Concurrent chemoradiotherapy (cCRT) is the standard of care for unresectable stage III NSCLC, but whether <em>EGFR</em> mutation is a prognostic factor remains unclear. This study evaluated the efficacy and safety of cCRT in unresectable stage III <em>EGFR</em>-mutant NSCLC. This study aimed to describe and compare the efficacy and safety outcomes of patients with unresectable stage III NSCLC treated with cCRT in those with and without <em>EGFR</em> mutation.</div></div><div><h3>Methods</h3><div>Data from three randomized phase II trials in the Japan Lung Cancer Society database (n = 274; 116 <em>EGFR</em> mutant, 158 <em>EGFR</em> wild type) were analyzed. Outcomes were progression-free survival (PFS), overall survival, and safety.</div></div><div><h3>Results</h3><div>Patients with <em>EGFR</em>-mutant NSCLC exhibited significantly shorter PFS than patients with <em>EGFR</em> wild-type NSCLC (hazard ratio [HR] = 1.38; 95% confidence interval [CI]: 1.05–1.82; <em>p</em> = 0.021). The results were generally consistent without statistical deviation, regardless of subgroup characteristics. <em>EGFR</em> mutation was retained as a covariate in the final multivariate model for PFS (HR = 1.358; 95% CI: 0.977–1.886; <em>p</em> = 0.068). Overall survival was not significantly different between the groups (HR = 0.98; 95% CI: 0.70–1.38; <em>p</em> = 0.903). A higher incidence of grades 3 to 4 pneumonitis was observed in patients with <em>EGFR</em>-mutant NSCLC compared with patients with <em>EGFR</em> wild-type NSCLC (7.8% versus 2.6%).</div></div><div><h3>Conclusion</h3><div>Patients with <em>EGFR</em>-mutant unresectable stage III NSCLC exhibited significantly shorter PFS than patients with <em>EGFR</em> wild-type NSCLC. The median PFS was generally consistent with that of the control arm in the LAURA trial. Increased pneumonitis risk necessitates close monitoring in patients with <em>EGFR</em>-mutant unresectable stage III NSCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100897"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388197","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":"Corrigendum to ‘First Central Asian Forum on Lung Cancer’ [JTO Clinical and Research Reports Volume 7 Issue 1 (2026) 100898]","authors":"Jandos Amankulov MD, PhD ,&nbsp;David F. Yankelevitz MD ,&nbsp;Amangeldi Mukhamejan MD ,&nbsp;Rowena Yip PhD, MPH ,&nbsp;Emanuela Taioli MD, PhD ,&nbsp;Bruce Pyenson FSA, MAAA ,&nbsp;James Mulshine MD ,&nbsp;Claudia I. Henschke PhD, MD","doi":"10.1016/j.jtocrr.2025.100948","DOIUrl":"10.1016/j.jtocrr.2025.100948","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100948"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147387786","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":"Pulmonary Malignancies in Adults With Congenital Lung Malformations: A Scoping Review","authors":"Louis W.J.R. Dossche MD ,&nbsp;M.H.T. Heuff BSc ,&nbsp;A.M. Heijne den Bak MD ,&nbsp;A.C. Dingemans MD, PhD ,&nbsp;L.S. Kamphuis MD, PhD ,&nbsp;J. Marco Schnater MD, PhD","doi":"10.1016/j.jtocrr.2026.100958","DOIUrl":"10.1016/j.jtocrr.2026.100958","url":null,"abstract":"<div><div>We aimed to synthesize current knowledge on pulmonary malignancies in adults with congenital lung malformations (CLMs), focusing on clinical presentation, treatment approaches, and outcomes.</div><div>We performed a scoping review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. A systematic search was conducted in January 2025 across three databases. References were included if they described patients aged 17 years or older with a CLM and a coexisting pulmonary malignancy. Data were extracted on patient demographics, CLM and malignancy type, symptoms, treatment, and outcomes. Findings were summarized using descriptive statistics and narrative synthesis.</div><div>A total of 65 references met the inclusion criteria, comprising 85 adult patients with CLM and pulmonary malignancies. Pulmonary adenocarcinoma was most frequently observed (66%), particularly within congenital pulmonary airway malformations (89% of malignancies in that subgroup). The median age at lung cancer diagnosis was 43.5 years. Respiratory symptoms were the most common presentation (67%), with 18% of patients being asymptomatic at the time of pulmonary malignancy diagnosis. Surgical resection was performed in 94% of patients, with lobectomy being the most frequently performed surgery type (68% of operated patients). More than half of malignancies (57%) were definitively diagnosed postoperatively. Follow-up data were incomplete; however, most reported patients were alive without disease recurrence at last follow-up with a median follow-up time of 14 months.</div><div>The young median age at cancer diagnosis, the presence of pulmonary malignancies in asymptomatic patients, and the high proportion of malignancy diagnoses established only postoperatively underscore the need for proactive and tailored surveillance strategies in adults with known CLM. A multidisciplinary approach with longitudinal follow-up is crucial to refine risk assessment and optimize long-term care.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100958"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147387787","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":"Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies","authors":"Montse Sanchez-Cespedes PhD ,&nbsp;William W. Lockwood PhD ,&nbsp;Kenichi Suda MD, PhD ,&nbsp;Eric E. Gardner PharmD, PhD ,&nbsp;Tetsuya Mitsudomi MD, PhD ,&nbsp;Katerina Politi PhD ,&nbsp;Christian Rolfo MD, PhD, MBA ,&nbsp;Triparna Sen PhD ,&nbsp;Martin L. Sos MD, PhD ,&nbsp;Tuomas Tammela MD, PhD ,&nbsp;Murry W. Wynes PhD ,&nbsp;Ming Sound Tsao MD, FRCPC ,&nbsp;Alice H. Berger PhD","doi":"10.1016/j.jtocrr.2025.100944","DOIUrl":"10.1016/j.jtocrr.2025.100944","url":null,"abstract":"<div><div>The discovery of <em>EGFR</em> mutations two decades ago launched an era of rapid development and clinical application of targeted therapies in NSCLC. Today, increasing numbers of targeted therapies against somatic aberrations involving nine different genes have become available for treating patients with lung cancer and have improved their outcomes. However, acquired resistance and tumor tolerance to these therapies remains one of the biggest challenges in lung cancer treatment today. Most, if not all, targeted therapies have limited durability, which we now recognize is due to both genetic and non-genetic mechanisms of resistance. The state of our current understanding of resistance and new approaches to prevent or overcome resistance were recently presented at the International Association for the Study of Lung Cancer Hot Topics Meeting. Here, we summarize and discuss the emerging concepts and new strategies for combating drug tolerance and resistance in targeted therapies, including our understanding of the role of genetics, drug-tolerant persister cells, tumor plasticity and lineage transformation, spatial and temporal heterogeneity, microenvironmental influence, and novel therapeutic approaches.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100944"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147387788","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: Multi-Institution Real-World Analysis Evaluating Safety, Efficacy, and ctDNA Dynamics After Tarlatamab in Patients With Previously Treated SCLC and LCNEC","authors":"Graeme Fenton MD ,&nbsp;Annie L. Zhang MD ,&nbsp;Sharon Zhong PharmD ,&nbsp;Curtis Tatsuoka PhD ,&nbsp;Michelle Sittig RN, OCN ,&nbsp;Alexandra Simms PharmD, BCOP ,&nbsp;Ranee Mehra MD ,&nbsp;Afshin Dowlati MD ,&nbsp;Taofeek K. Owonikoko MD, PhD ,&nbsp;Katherine Scilla MD ,&nbsp;Melinda Hsu MD ,&nbsp;Samuel Rosner MD","doi":"10.1016/j.jtocrr.2025.100933","DOIUrl":"10.1016/j.jtocrr.2025.100933","url":null,"abstract":"<div><div>Tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 and CD3 on T cells, has generated impressive treatment response rates in relapsed extensive-stage SCLC and large cell neuroendocrine carcinoma. We performed a retrospective, multi-institutional analysis of 48 patients who received tarlatamab as standard of care to assess how safety and efficacy outcomes translate into real-world practice. Rates of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were 54% and 33%, respectively, with most being grades 1 to 2 in severity (100% and 87.5%). Of the 30 patients included in our efficacy analysis, the best overall response rate was 67% and disease control rate was 73%. With median follow-up of 5.7 months, median progression-free survival was 4.9 months (95% confidence interval: 4–not reached) and median overall survival was not reached (95% confidence interval: 4.8–not reached). Nine patients underwent molecular response assessment, with circulating tumor DNA trends corresponding with radiographic response. In this multicenter cohort study, tarlatamab continued to demonstrate encouraging response rates and progression-free survival; however, differences were observed in rates and timing of key treatment-associated toxicities compared with previous trial data.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100933"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147387789","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":"Definitive Radiotherapy With or Without Chemotherapy After Planned Neoadjuvant Chemoimmunotherapy in Stages II to III NSCLC: An International Multicenter Retrospective Study","authors":"Elio Adib MD ,&nbsp;Amin H. Nassar MD ,&nbsp;Katie N. Lee MD, PhD ,&nbsp;Francesca Fusco MD ,&nbsp;Fionnuala Crowley MD ,&nbsp;Javier Baena MD ,&nbsp;John Emmett Worth BS ,&nbsp;Joseph Abi Jaoude MD ,&nbsp;Alfredo Addeo MD ,&nbsp;Elias Bou Farhat MD ,&nbsp;Mehrdad Rakaee PhD ,&nbsp;Arya Amini MD ,&nbsp;Jason Lambden MD ,&nbsp;Maximilian Rost MD ,&nbsp;Iakov Bolnykh MD ,&nbsp;Frank Aboubakar Nana MD ,&nbsp;Avinash Aujayeb MD ,&nbsp;Alessio Cortellini MD, PhD ,&nbsp;Thomas Newsom-Davis M.B.B.S., PhD ,&nbsp;D. Ross Camidge MD, PhD ,&nbsp;Florence K. Keane MD","doi":"10.1016/j.jtocrr.2025.100949","DOIUrl":"10.1016/j.jtocrr.2025.100949","url":null,"abstract":"<div><h3>Introduction</h3><div>Approximately 15% to 20% of patients with resectable NSCLC receiving neoadjuvant chemoimmunotherapy on clinical trials cannot proceed to surgery due to disease progression, toxicity, or medical contraindications. The safety and efficacy of definitive radiotherapy (RT) in this population are uncertain.</div></div><div><h3>Methods</h3><div>We performed an international multicenter (13 institutions) retrospective study of patients with stages II to III NSCLC who received more than or equal to 2 cycles of neoadjuvant platinum-based chemoimmunotherapy followed by definitive RT instead of planned surgery. The primary end point was pneumonitis incidence; secondary end points included progression-free survival (PFS), overall survival (OS), and treatment-related adverse events.</div></div><div><h3>Results</h3><div>We identified 57 patients, 54 (90%) of whom had stage III NSCLC. The most common reasons for definitive RT were surgical resectability (n = 38, 67%), followed by new-onset medical contraindications (n = 15, 26%), patient preference (n=3, 5%), and complete radiographic response (n = 1, 2%). Pneumonitis occurred in 10 patients (18%), including six grade 3 to 4 events (10.5%) and one grade 5 event (2%), with no differences based on concurrent chemotherapy or consolidation systemic therapy. Most patients (n = 36, 63%) achieved partial radiographic response to neoadjuvant therapy. With median follow-up of 17 months, median PFS was 16.1 months (95% confidence interval [CI] 12.2–not reached [NR]) and median OS was not reached (interquartile range 20.5–NR). One-year OS rate was 81% (95% CI 70%–94%). PFS was longer in patients undergoing RT for medical contraindications versus surgical resectability (30.3 [95% CI 16.1–NR] versus 12.2 [95% CI 7.6–NR] mo; <em>p</em> = 0.037). No significant differences in PFS were observed with concurrent chemotherapy (<em>p</em> = 0.64) or consolidation therapy (<em>p</em> = 0.12). Among 27 patients experiencing progression after definitive RT, the most common site was the lungs (n = 19, 70.4%), followed by lymph nodes (n = 8, 29.6%) and bone (n = 5, 18.5%).</div></div><div><h3>Conclusion</h3><div>Definitive RT after neoadjuvant chemoimmunotherapy demonstrates promising effectiveness and safety in patients unable to undergo planned surgery. Prospective studies should focus on adaptive RT approaches and biomarker development to improve outcomes in this challenging population.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100949"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147387790","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 Plus Chemotherapy in Patients With EGFR-Mutated Advanced NSCLC Whose Disease Progressed on First-Line Osimertinib: ORCHARD","authors":"Byoung Chul Cho MD, PhD ,&nbsp;Makoto Nishio MD, PhD ,&nbsp;Myung-Ju Ahn MD, PhD ,&nbsp;Rosario García-Campelo MD ,&nbsp;Santiago Ponce MD ,&nbsp;Christina Baik MD, MPH ,&nbsp;Ravi Salgia MD, PhD ,&nbsp;Sang-We Kim MD, PhD ,&nbsp;Jong Seok Lee MD ,&nbsp;Tatsuya Yoshida MD, PhD ,&nbsp;Helena A. Yu MD ,&nbsp;Sarah B. Goldberg MD, MPH ,&nbsp;Adrianus Johannes de Langen MD, PhD ,&nbsp;Xiuning Le MD, PhD ,&nbsp;Zofia Piotrowska MD, MHS ,&nbsp;Jonathan W. Riess MD, MS ,&nbsp;Kentaro Tanaka MD, PhD ,&nbsp;Helen Ambrose PhD ,&nbsp;Jan Cosaert MD, PhD ,&nbsp;Paula G. Fraenkel MD ,&nbsp;Jonathan W. Goldman MD","doi":"10.1016/j.jtocrr.2025.100937","DOIUrl":"10.1016/j.jtocrr.2025.100937","url":null,"abstract":"<div><h3>Introduction</h3><div>ORCHARD (NCT03944772) was a phase II, biomarker-directed platform study designed to characterize resistance mechanisms and evaluate novel therapy combinations after progressive disease (PD) on first-line osimertinib. We report results of the module assessing durvalumab plus chemotherapy.</div></div><div><h3>Methods</h3><div>Patients with epidermal growth factor receptor (<em>EGFR</em>)-mutated non-small cell lung cancer (NSCLC) with PD on first-line osimertinib whose tumors did not harbor a prespecified alteration by next-generation sequencing of a post-osimertinib biopsy, or for whom a biomarker-matched treatment was not available, were eligible. Patients received 4 to 6 cycles of durvalumab 1500 mg plus carboplatin target area under the curve 5 and pemetrexed 500 mg/m². After platinum-based chemotherapy, patients without PD could continue to receive durvalumab plus pemetrexed maintenance. Primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator assessment.</div></div><div><h3>Results</h3><div>Overall, 25 patients received more than or equal to 1 dose of durvalumab plus chemotherapy; all had discontinued treatment at the primary analysis data cutoff. Confirmed ORR was 16% (80% confidence interval [CI]: 7–30); response was maintained for more than 6 months in the four patients with confirmed response. Furthermore, 22 patients (88%) had PD and median progression-free survival was 4.8 months (95% CI: 2.6–7.6). Ten patients (40%) had died, and median overall survival was 23.4 months (95% CI: 8.8–not calculable). Nine patients (36%) had grade 3 or higher adverse events, most often neutrophil count decreased (20%).</div></div><div><h3>Conclusions</h3><div>Durvalumab plus chemotherapy demonstrated limited clinical benefit for <em>EGFR</em>-mutated NSCLC after PD on first-line osimertinib. Although the combination was well tolerated, the overall risk-benefit profile did not warrant further evaluation.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"7 4","pages":"Article 100937"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147703223","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}