Journal of Clinical Oncology最新文献

{"title":"Management of Patients With <i>EGFR</i> Exon 20-Mutant Advanced Non-Small Cell Lung Cancer.","authors":"Lova Sun, Melina E Marmarelis, Charu Aggarwal","doi":"10.1200/JCO-24-02624","DOIUrl":"https://doi.org/10.1200/JCO-24-02624","url":null,"abstract":"<p><p><i>The Oncology Grand Rounds series is designed to place original reports published in the</i> Journal <i>into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in</i> Journal of Clinical Oncology<i>, to patients seen in their own clinical practice.</i></p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402624"},"PeriodicalIF":42.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases.","authors":"Sarah A Weiss, Dijana Djureinovic, Wei Wei, Thuy Tran, Matthew Austin, Joseph Markowitz, Zeynep Eroglu, Nikhil I Khushalani, Upendra Hegde, Justine Cohen, Mario Sznol, Gail Anderson, Barbara Johnson, Cecily Piteo, Amit Mahajan, Adebowale Adeniran, Lucia Jilaveanu, Sarah Goldberg, Veronica Chiang, Peter Forsyth, Harriet M Kluger","doi":"10.1200/JCO-24-02219","DOIUrl":"10.1200/JCO-24-02219","url":null,"abstract":"<p><strong>Purpose: </strong>Anti-vascular endothelial growth factor therapy enhances PD-1 inhibitor activity in preclinical models and has been used to treat perilesional cerebral edema and radiation necrosis.</p><p><strong>Methods: </strong>We conducted a two-institution phase II trial of bevacizumab and pembrolizumab in patients with untreated melanoma brain metastasis (MBM) (ClinicalTrials.gov identifier: NCT02681549). Patients were anti-PD-(L)-1-naïve, and had ≥one asymptomatic, nonhemorrhagic 5-20 mm MBM, not requiring immediate local therapy or steroids.</p><p><strong>Results: </strong>Thirty-seven patients received four doses of bevacizumab and pembrolizumab every 3 weeks followed by up to 2 years of pembrolizumab. The brain metastasis response rate (primary end point) was 54.1% (95% CI, 36.9 to 70.5). The extracranial response rate was 56.3% (95% CI, 37.7 to 73.6). Median intracranial progression-free survival was 2.2 years (95% CI, 0.41 to not reached [NR]). Median overall survival (OS) was 4.3 years (95% CI, 1.6 to NR). Four-year OS rate was 51.6%. Grade 3 treatment-related adverse event rates from bevacizumab and pembrolizumab were 10.8% and 18.9%, respectively. Higher pretreatment vessel density in metastatic tumors and smaller on-therapy increases in circulating angiopoietin-2 were associated with response.</p><p><strong>Conclusion: </strong>Pembrolizumab with bevacizumab was well tolerated and demonstrated substantial activity in patients with untreated MBM with promising OS, justifying further evaluation of this regimen.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402219"},"PeriodicalIF":42.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data, Models, and Visuals: How Data Science Methods Can Augment (Geriatric) Oncology Research.","authors":"Erika Ramsdale, Supriya Mohile","doi":"10.1200/JCO-25-00053","DOIUrl":"https://doi.org/10.1200/JCO-25-00053","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500053"},"PeriodicalIF":42.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating Myeloma Drug Development: Will Minimal Residual Disease Replace Progression-Free Survival as an Intermediate Surrogate End Point?","authors":"María-Victoria Mateos, Noemí Puig","doi":"10.1200/JCO-25-00048","DOIUrl":"https://doi.org/10.1200/JCO-25-00048","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500048"},"PeriodicalIF":42.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized, Open-Label, Phase III Study of Tilsotolimod in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced Refractory Melanoma (ILLUMINATE-301).","authors":"Adi Diab, Paolo A Ascierto, Michele Maio, Reham Abdel-Wahab, Sylvie Negrier, Laurent Mortier, Petr Arenberger, Stephane Dalle, Ivana Krajsova, Luis de la Cruz, Marie-Therese Leccia, Michele Guida, Celeste Lebbe, Jean-Jacques Grob, Marcus O Butler, Gino K In, Carmen Loquai, John W T Walker, Victoria Atkinson, Ellen Kapiteijn, Sebastian Haferkamp, Srinivas Chunduru, Shahram Rahimian, Massimo Guidoboni, Caroline Robert","doi":"10.1200/JCO.24.00727","DOIUrl":"https://doi.org/10.1200/JCO.24.00727","url":null,"abstract":"<p><strong>Purpose: </strong>There are limited treatment options for advanced melanoma that have progressed during or after immune checkpoint inhibitor therapy. Intratumoral (IT) immunotherapy may improve tumor-specific immune activation by promoting local tumor antigen presentation while avoiding systemic toxicities. The phase 3 ILLUMINATE-301 study (ClinicalTrials.gov identifier: NCT03445533) evaluated tilsotolimod, a Toll-like receptor-9 agonist, with or without ipilimumab in patients with anti-PD-1 advanced refractory melanoma.</p><p><strong>Methods: </strong>Patients with unresectable stage III-IV melanoma that progressed during or after anti-PD-1 therapy were randomly assigned 1:1 to receive 24 weeks of tilsotolimod plus ipilimumab or 10 weeks of ipilimumab alone. Nine IT injections of tilsotolimod were administered to a single designated lesion over 24 weeks. Intravenous ipilimumab 3 mg/kg was administered once every 3 weeks from week 2 in the tilsotolimod arm and week 1 in the ipilimumab arm. The primary end point was efficacy measured using objective response rate (ORR; independent review) and overall survival (OS).</p><p><strong>Results: </strong>A total of 481 patients received tilsotolimod plus ipilimumab (n = 238) or ipilimumab alone (n = 243). ORRs were 8.8% in the tilsotolimod arm and 8.6% in the ipilimumab arm, with disease control rates of 34.5% and 27.2%, respectively. Median OS was 11.6 months in the tilsotolimod arm and 10 months in the ipilimumab arm (hazard ratio, 0.96 [95% CI, 0.77 to 1.19]; <i>P</i> = .7). Grade ≥3 treatment-emergent adverse events occurred in 61.1% and 55.5% of patients in the tilsotolimod and ipilimumab arms, respectively.</p><p><strong>Conclusion: </strong>Combining IT tilsotolimod with ipilimumab did not significantly improve the ORR or OS compared with ipilimumab alone in patients with anti-PD-1 advanced refractory melanoma.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2400727"},"PeriodicalIF":42.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Randomized Comparison of Intensified Six-Drug Versus Standard Three-Drug Chemotherapy for High-Risk Nonmetastatic Rhabdomyosarcoma and Other Chemotherapy-Sensitive Childhood Soft Tissue Sarcomas: Long-Term Results From the International Society of Pediatric Oncology MMT95 Study.","authors":"Odile Oberlin, Annie Rey, José Sanchez de Toledo, Hélène Martelli, Meriel E M Jenney, Marcelo Scopinaro, Christophe Bergeron, Johannes H M Merks, Nathalie Bouvet, Caroline Ellershaw, Anna Kelsey, David Spooner, Michael C G Stevens","doi":"10.1200/JCO-25-00440","DOIUrl":"https://doi.org/10.1200/JCO-25-00440","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500440"},"PeriodicalIF":42.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab Plus Docetaxel Versus Docetaxel for Previously Treated Metastatic Castration-Resistant Prostate Cancer: The Randomized, Double-Blind, Phase III KEYNOTE-921 Trial.","authors":"Daniel P Petrylak, Raffaele Ratta, Nobuaki Matsubara, Ernesto Korbenfeld, Rustem Gafanov, Loic Mourey, Tilman Todenhöfer, Howard Gurney, Gero Kramer, Andries M Bergman, Pawel Zalewski, Maria De Santis, Andrew J Armstrong, Winald Gerritsen, Russell Pachynski, Seok Soo Byun, Margitta Retz, Eric Levesque, Ray McDermott, Sergio Bracarda, Ray Manneh, Meital Levartovsky, Xin Tong Li, Charles Schloss, Christian H Poehlein, Karim Fizazi","doi":"10.1200/JCO-24-01283","DOIUrl":"https://doi.org/10.1200/JCO-24-01283","url":null,"abstract":"<p><strong>Purpose: </strong>The standard of care for metastatic castration-resistant prostate cancer (mCRPC) after second-generation androgen receptor pathway inhibitor (ARPI) therapy is still docetaxel. The randomized, double-blind, phase III KEYNOTE-921 trial (Clinicaltrials.gov identifier: NCT03834506) evaluated the efficacy and safety of pembrolizumab or placebo plus docetaxel for previously treated mCRPC.</p><p><strong>Methods: </strong>Adults with mCRPC who progressed after androgen-deprivation therapy and one ARPI were randomly assigned 1:1 to pembrolizumab or placebo plus docetaxel with concomitant prednisone. Dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group 3-modified RECIST 1.1 and overall survival (OS). Safety was a secondary end point.</p><p><strong>Results: </strong>Between May 30, 2019, and June 17, 2021, 515 participants were randomly assigned to pembrolizumab plus docetaxel and 515 to placebo plus docetaxel. Median time from random assignment to data cutoff date (June 20, 2022) at final analysis (FA) was 22.7 months (range, 12.1-36.7). At first interim analysis (data cutoff date: September 27, 2021), median rPFS was 8.6 months (95% CI, 8.3 to 10.2) with pembrolizumab plus docetaxel versus 8.3 months (95% CI, 8.2 to 8.5) with placebo plus docetaxel (hazard ratio [HR], 0.85 [95% CI, 0.71 to 1.01]; <i>P</i> = .03). At FA, median OS was 19.6 months (95% CI, 18.2 to 20.9) versus 19.0 months (95% CI, 17.9 to 20.9), respectively (HR, 0.92 [95% CI, 0.78 to 1.09]; <i>P</i> = .17). Grade ≥3 treatment-related adverse events occurred in 43.2% of participants who received pembrolizumab plus docetaxel and 36.6% of participants who received placebo plus docetaxel. Two and seven participants, respectively, died due to a treatment-related adverse event. Pneumonitis was the most common immune-mediated adverse event (7.0% <i>v</i> 3.1%).</p><p><strong>Conclusion: </strong>The addition of pembrolizumab to docetaxel did not significantly improve efficacy outcomes for participants with previously treated mCRPC. The current standard of care remains unchanged.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401283"},"PeriodicalIF":42.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explaining the Relationships Between Age, Endocrine Therapy Persistence, and Risk of Recurrence in Hormone Receptor-Positive Early Breast Cancer: A Nationwide Cohort Study.","authors":"Elise Dumas, Floriane Jochum, Florence Coussy, Anne-Sophie Hamy, Alena Majdling, Sophie Houzard, Christine Le Bihan-Benjamin, Fabien Reyal, Paul Gougis, Mats Julius Stensrud","doi":"10.1200/JCO.24.01131","DOIUrl":"https://doi.org/10.1200/JCO.24.01131","url":null,"abstract":"<p><strong>Purpose: </strong>Young age is associated with increased risk of recurrence in hormone receptor (HR)-positive early-stage breast cancer (eBC). Lack of adherence to endocrine therapy (ET) is a potential reason for the lower survival proportions observed in younger patients, but the survival benefits of improving adherence to ET in young patients remain unknown.</p><p><strong>Materials and methods: </strong>Using data from the French National Health Data System and target trial emulation methods, we considered three sustained ET persistence strategies (allowing treatment gaps of no more than 30, 90, or 180 continuous days) and estimated the 5-year disease-free survival (DFS) benefit of sustained ET persistence compared with observed ET persistence.</p><p><strong>Results: </strong>A total of 121,601 patients with HR-positive eBC were included in the analyses, of whom 29.8% was younger than 50 years at diagnosis. Younger patients had lower DFS and were more likely to discontinue ET than older patients. In patients 34 years and younger, strict ET persistence (≤30-day gaps) improved 5-year DFS proportions from 74.5% to 78.8% (4.3 percentage points [95% CI, 2.6 to 7.2]) compared with observed persistence. ET persistence strategies allowing for ≤90-day and ≤180-day gaps reduced the 5-year DFS benefit in patients 34 years and younger to 1.3 (95% CI, 0.2 to 3.7) and 1.0 (95% CI, -0.2 to 3.4) percentage points, respectively. By contrast, DFS benefits of improved ET persistence in patients after 50 years old did not exceed 1.9 percentage points, compared with observed persistence, regardless of the persistence definition.</p><p><strong>Conclusion: </strong>The survival benefit that could be achieved with strict ET persistence in women 34 years and younger with HR-positive eBC highlights the need for tailored strategies to improve ET persistence in this population.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401131"},"PeriodicalIF":42.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency and Clinical Significance of Clonal and Subclonal Driver Mutations in High-Risk Neuroblastoma at Diagnosis: A Children's Oncology Group Study.","authors":"Esther R Berko, Arlene Naranjo, Alexander A Daniels, Samantha N McNulty, Kateryna Krytska, Todd Druley, Kirstin Zelley, Balakrishna Koneru, Lulu Chen, Grace Polkosnik, Meredith S Irwin, Rochelle Bagatell, John M Maris, C Patrick Reynolds, Steven G DuBois, Julie R Park, Yael P Mossé","doi":"10.1200/JCO-24-02407","DOIUrl":"10.1200/JCO-24-02407","url":null,"abstract":"<p><strong>Purpose: </strong>Relapsed high-risk neuroblastomas (NBLs) are enriched for targetable mutations in <i>ALK</i> and RAS-MAPK pathways, yet the prognostic effect of these aberrations and relevance of subclonal mutations at diagnosis remain undefined. We describe the spectrum and clinical significance of clonal and subclonal pathogenic alterations in high-risk NBL.</p><p><strong>Methods: </strong>We developed a focused high-risk NBL sequencing panel including <i>ALK</i>, <i>NRAS</i>, <i>KRAS</i>, <i>HRAS</i>, <i>BRAF</i>, <i>PTPN11</i>, <i>TP53</i>, and <i>ATRX</i> genes for ultra-deep sequencing and applied this assay to 242 pretherapy tumors from patients enrolled on the phase III trial Children's Oncology Group ANBL0532. We assessed the effect of clonal and subclonal mutations on event-free survival (EFS) and overall survival (OS).</p><p><strong>Results: </strong><i>ALK</i>-activating mutations occurred in 21.5% of tumors (n = 52, 30 clonal, 22 subclonal), and 3.3% (n = 8) showed <i>ALK</i> amplification. EFS and OS for patients with any <i>ALK</i>-aberrant tumor were inferior to patients with wild-type (WT) <i>ALK</i> tumors (5-year OS 37.7% <i>v</i> 66.3%; hazard ratio [HR], 1.992; <i>P</i> = .0007). EFS and OS for patients with tumors harboring activating <i>ALK</i> mutations ≥5% variant allele frequency (VAF) were inferior to <i>ALK</i> WT (5-year OS 37.7% <i>v</i> 66.3%; HR, 1.966; <i>P</i> = .0041). The 5-year EFS and OS for patients with <i>ALK</i>-amplified tumors were 25.0%. RAS pathway mutations occurred in 7.9% of tumors (n = 19; four clonal, 15 subclonal), with EFS and OS for those with VAF ≥5% inferior to RAS-WT patients (5-year OS 19.1% <i>v</i> 60.0%; HR, 3.021; <i>P</i> = .0168).</p><p><strong>Conclusion: </strong>Ultra-deep sequencing of high-risk NBLs demonstrates that oncogenic aberrations are more prevalent at diagnosis than previously recognized. <i>ALK</i> and RAS pathway aberrations confer inferior outcomes in patients treated with contemporary therapy, emphasizing the need for novel therapeutic approaches.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2402407"},"PeriodicalIF":42.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors With <i>HER2</i> Alterations: A Phase Ia Dose-Escalation Study.","authors":"John V Heymach, Frans Opdam, Minal Barve, Hai-Yan Tu, Yi-Long Wu, David Berz, Lukas Schröter, Yanick Botilde, Behbood Sadrolhefazi, Josep Serra, Kiyotaka Yoh, Noboru Yamamoto","doi":"10.1200/JCO-24-01727","DOIUrl":"https://doi.org/10.1200/JCO-24-01727","url":null,"abstract":"<p><strong>Purpose: </strong>Human epidermal growth factor receptor 2 (HER2) alterations occur in many solid cancers, including non-small cell lung cancer (NSCLC). Beamion LUNG-1 (ClinicalTrials.gov identifier: NCT04886804) is assessing the safety/efficacy of zongertinib (BI 1810631), a novel HER2-selective tyrosine kinase inhibitor that spares epidermal growth factor receptor, in patients with HER2-altered solid tumors.</p><p><strong>Materials and methods: </strong>Beamion LUNG-1 is an ongoing multicenter, multicohort phase Ia/Ib trial. Phase Ia assessed zongertinib administered twice a day (15-150 mg) or once daily (60-360 mg) in pretreated patients with various tumors, including NSCLC. Primary end points were maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs); tumor response was a secondary end point.</p><p><strong>Results: </strong>As of May 23, 2024, 105 patients were treated. Two DLTs occurred during the MTD evaluation period; MTD was not reached (NR). The recommended doses for expansion were 120 mg once daily and 240 mg once daily. Treatment-related adverse events (TRAEs; any/grade ≥3) occurred in 82%/10% of patients. The most common TRAEs (any/grade ≥3) included diarrhea (50%/1%), rash (16%/2%), anemia (10%/0%), decreased appetite (10%/1%), and increased alanine transaminase (10%/4%). The confirmed investigator-assessed overall response rate (ORR) across all doses/tumors was 30% (95% CI, 23 to 40); median duration of response was 12.7 months (95% CI, 6.9 to NR). In 54 patients with NSCLC, confirmed ORR was 35% (95% CI, 24 to 49). Activity was observed in patients with A775_G776insYVMA (ORR, 38%) and those who had received previous HER2-directed therapy (ORR, 28%). In patients with NSCLC receiving zongertinib once daily, median progression-free survival was 17.2 months (95% CI, 8.3 to NR).</p><p><strong>Conclusion: </strong>Zongertinib had a manageable safety profile and demonstrated preliminary antitumor activity in patients with HER2-altered tumors, including those with <i>HER2</i>-mutant NSCLC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401727"},"PeriodicalIF":42.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}