Journal of Clinical Oncology最新文献

{"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":"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":"1863-1874"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","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":"Reply to: Reflections on the HORSE Trial: Hyperthermic Intraperitoneal Chemotherapy, <i>BRCA</i> Status, and Clinical Implications.","authors":"Gini F Fleming","doi":"10.1200/JCO-25-00155","DOIUrl":"10.1200/JCO-25-00155","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1932-1933"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630511","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":"Pasritamig, a First-in-Class, Bispecific T-Cell Engager Targeting Human Kallikrein 2, in Metastatic Castration-Resistant Prostate Cancer: A Phase I Study.","authors":"Mark N Stein, Armelle Vinceneux, Debbie Robbrecht, Bernard Doger, Karen A Autio, Michael T Schweizer, Emiliano Calvo, Laura Medina, Marloes Van Dongen, Jean-Laurent Deville, Alice Bernard-Tessier, Debopriya Ghosh, Kristin Shotts, Fei Shen, Pharavee Jaiprasart, Ruchi Chaudhary, Shujian Wu, Leanne Cartee, Robert Schnepp, Daria Gaut, Josh Lauring, Sherry C Wang, Victor M Villalobos, Capucine Baldini","doi":"10.1200/JCO-25-00678","DOIUrl":"10.1200/JCO-25-00678","url":null,"abstract":"<p><strong>Purpose: </strong>We report phase I trial results for pasritamig, a first-in-class, T-cell-engaging bispecific antibody targeting human kallikrein 2 (KLK2) expressed on the surface of prostate cancer (PC) cells.</p><p><strong>Methods: </strong>Participants had metastatic castration-resistant PC and ≥1 prior therapy. Pasritamig was escalated from 0.5 mg to 2,000 mg for subcutaneous administration and from 150 mg to 900 mg for intravenous (IV) administration at dosing frequencies ranging from once every week to once every 6 weeks with different step-up dosing schedules. The primary objectives were to determine safety and the recommended phase II dose (RP2D) of pasritamig. Secondary objectives included preliminary assessment of antitumor activity.</p><p><strong>Results: </strong>One hundred seventy-four participants received pasritamig, with a median of 4 prior lines of systemic therapy. Treatment-related adverse events (TRAEs) occurred in 144 of 174 (82.8%) participants, with 17 of 174 (9.8%) experiencing grade ≥3 TRAEs. The RP2D was determined to be 3.5 mg (day 1), 18 mg (day 8), 300 mg (day 15), and then 300 mg IV once every 6 weeks. In the RP2D safety population (n = 45), infusion-related reactions (11/45, 24.4%), fatigue (7/45, 15.6%), cytokine release syndrome (CRS; 4/45, 8.9%, all grade 1), and lipase increase (4/45, 8.9%) were the most frequent TRAEs; all were grade 1 or 2. In the RP2D efficacy population (n = 33), median radiographic progression-free survival was 7.85 (95% CI, 2.89 to not estimable) months, and 14 of 33 (42.4%) participants achieved a ≥50% decrease from baseline in prostate-specific antigen.</p><p><strong>Conclusion: </strong>Pasritamig demonstrated a favorable safety profile with very low rates of CRS and could be safely administered in an outpatient setting. Preliminary antitumor activity demonstrated proof of concept for KLK2 as a target in PC, warranting further development of pasritamig.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500678"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199181","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":"What I Wish I Had Known: A Pediatric Oncologist's Transition to Survivorship Care.","authors":"Ana Carolina Izurieta-Pacheco","doi":"10.1200/JCO-24-02821","DOIUrl":"10.1200/JCO-24-02821","url":null,"abstract":"<p><p>This essay explores the often overlooked challenges of survivorship care, reflecting on the journey from pediatric oncology to supporting cancer survivors in navigating life after treatment.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1930-1931"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002426","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":"Reflections on the HORSE Trial: Hyperthermic Intraperitoneal Chemotherapy, <i>BRCA</i> Status, and Clinical Implications.","authors":"Hamdullah Sözen, Yagmur Minareci, Atahan Toyran, Mustafa Albayrak, Samet Topuz, Yavuz Salihoglu","doi":"10.1200/JCO-24-02635","DOIUrl":"10.1200/JCO-24-02635","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1932"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630548","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":"Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab.","authors":"Zofia Piotrowska, Antonio Passaro, Danny Nguyen, Gerrina Ruiter, Ross A Soo, Victor Ho-Fun Lee, Vamsidhar Velcheti, Daniel Shao-Weng Tan, Se-Hoon Lee, Se Hyun Kim, John Wrangle, James Chih-Hsin Yang, Haruko Daga, Oscar J Juan Vidal, Alexander I Spira, Gonzalo Fernandez-Hinojal, Sang-We Kim, Shigeki Umemura, Mariano Provencio Pulla, Erika K Keeton, Zhihui Sunny Yang, Shengting Li, Zhiying Cindy Xu, Jeffrey A Jones, Helena Alexandra Yu","doi":"10.1200/JCO-25-00763","DOIUrl":"10.1200/JCO-25-00763","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the safety and efficacy of zipalertinib, an irreversible epidermal growth factor receptor (EGFR) inhibitor, in pretreated patients with non-small cell lung cancer (NSCLC) harboring <i>EGFR</i> exon 20 insertion (ex20ins) mutations.</p><p><strong>Methods: </strong>REZILIENT1 (ClinicalTrials.gov identifier: NCT04036682) is a phase I/II open-label trial enrolling patients with locally advanced or metastatic <i>EGFR</i> ex20ins-mutant NSCLC previously treated with platinum-based chemotherapy with/without ex20ins-targeted therapies. Asymptomatic, treated and untreated stable CNS metastases are permitted. We report data from patients treated with zipalertinib 100 mg twice daily. The primary end points are objective response rate (ORR) and duration of response (DOR) by independent central review.</p><p><strong>Results: </strong>At data cutoff (December 10, 2024), 244 patients had received treatment with zipalertinib 100 mg twice daily. The primary efficacy population (8 months' follow-up) comprised patients who had received prior platinum-based chemotherapy without ex20ins-targeted therapy (125 patients), with amivantamab only (30 patients), or with amivantamab and other ex20ins-targeted therapy (21 patients). The confirmed ORR was 35.2% (95% CI, 28.2 to 42.8); median DOR was 8.8 months (95% CI, 8.3 to 12.7). Among patients who received prior platinum-based chemotherapy without ex20ins-targeted therapy, amivantamab only, or amivantamab and other ex20ins-targeted therapy, the confirmed ORR was 40%, 30%, and 14.3%, and median DOR was 8.8, 14.7, and 4.2 months, respectively. Among 68 patients with CNS metastases, the ORR was 30.9%. The most common grade ≥3 treatment-related adverse events were anemia (7%), pneumonitis and rash (2.5% each), and diarrhea, ALT increased, and platelet count decreased (2% each).</p><p><strong>Conclusion: </strong>Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with <i>EGFR</i> ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500763"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199183","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":"Use of Low-Value Cancer Treatments in Medicare Advantage Versus Traditional Medicare.","authors":"Jeah Jung, Caroline Carlin, Roger Feldman, Ge Song, Aaron Mitchell","doi":"10.1200/JCO-24-01907","DOIUrl":"https://doi.org/10.1200/JCO-24-01907","url":null,"abstract":"<p><strong>Purpose: </strong>Medicare Advantage (MA) provides beneficiaries an option to receive Medicare benefits from private plans. Although MA covers over half of the Medicare population, limited information exists about how utilization of cancer treatments in MA differs from traditional Medicare (TM). We compared use of low-value cancer treatments between MA and TM and analyzed variation in use of low-value cancer treatments across large MA insurers.</p><p><strong>Methods: </strong>Using national Medicare data, we performed retrospective analyses of beneficiaries who had a new cancer diagnosis between 2016 and 2021 and who were at risk of receiving a low-value treatment: granulocyte-colony stimulating factors (GCSFs) for patients receiving low-risk chemotherapy, denosumab for castration-sensitive prostate cancer (CSPC), nab-paclitaxel instead of paclitaxel for breast or lung cancers, adding bevacizumab to carboplatin plus paclitaxel for ovarian cancer, and branded drugs or biologics for which generic or biosimilar versions existed.</p><p><strong>Results: </strong>Use of any low-value cancer treatment was 1.7 percentage points lower in MA than in TM (34.2% <i>v</i> 35.9%; <i>P</i> < .001). MA had lower utilization rates than TM for GCSF among patients receiving low-risk chemotherapy (7.3% <i>v</i> 8.9%; <i>P</i> < .001), denosumab for CSPC (26.4% <i>v</i> 33.1%; <i>P</i> < .001), nab-paclitaxel for breast or lung cancer (7.9% <i>v</i> 8.7%; <i>P</i> < .001), addition of bevacizumab for ovarian cancer (8.3% <i>v</i> 10.5%; <i>P</i> < .001), and biologics with biosimilar alternatives (66.8% <i>v</i> 68.5%; <i>P</i> < .001). Use of branded drugs did not significantly differ between MA and TM. The differences in use of low-value cancer treatments from TM varied moderately across large MA insurers.</p><p><strong>Conclusion: </strong>MA has lower use of low-value cancer treatments than TM, with varying degrees across large MA insurers. Efforts are needed to identify effective strategies to reduce use of low-value cancer treatments.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2401907"},"PeriodicalIF":42.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191862","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 (Alliance A091802) Randomized Trial of Avelumab Plus Cetuximab Versus Avelumab Alone in Advanced Cutaneous Squamous Cell Carcinoma.","authors":"Dan P Zandberg, Jacob B Allred, Ari J Rosenberg, John M Kaczmar, Paul Swiecicki, Ricklie A Julian, Andrew S Poklepovic, Jessica R Bauman, Minh D Phan, Nabil F Saba, Edgardo Rivera, Kendrith Rowland, Diwakar Davar, Julia Cordes, Alan L Ho, Miao Zhang, Stephanie A Berg, Pamela N Munster, Gary K Schwartz","doi":"10.1200/JCO-25-00759","DOIUrl":"https://doi.org/10.1200/JCO-25-00759","url":null,"abstract":"<p><strong>Purpose: </strong>Continued improvement in outcomes is needed for advanced cutaneous squamous cell carcinoma (cSCC).</p><p><strong>Methods: </strong>Alliance A091802 is a randomized phase II trial of avelumab (800 mg IV once every 2 weeks) plus cetuximab (500 mg/m² IV once every 2 weeks) versus avelumab alone once every 2 weeks for up to 2 years. Cetuximab was given for 1 year in the avelumab + cetuximab arm. Crossover at progression to avelumab + cetuximab was allowed. Randomization was 1:1, stratified by PD-L1 and HIV status. Patients had distant metastatic or unresectable locally advanced cSCC, were anti-PD-1/PD-L1 monoclonal antibody-naive, had no previous cetuximab in the advanced setting, had an Eastern Cooperative Oncology Group performance status of 0-2, and could be HIV+ (CD4 >200, viral load <200). Patients with chronic lymphocytic leukemia, immunosuppression, or active autoimmune diseases were excluded. The primary end point was progression-free survival (PFS; null hypothesis: median = 12 months <i>v</i> alternative hypothesis: 21 months or a 75% improvement, power of 80% with one-sided alpha .2, n = 57, 37 PFS events required). Secondary end points were overall survival, objective response rates (ORRs), clinical benefit rate, and toxicity.</p><p><strong>Results: </strong>Sixty patients were enrolled; 57 patients were evaluable. The median age was 72 years, all were HIV-; 75.4% was PD-L1+, 84.2% had head/neck origin, 47.4% had distant metastasis, and there were no differences in baseline characteristics by arm. Avelumab + cetuximab significantly improved PFS versus avelumab (median, 11.1 [7.6-not reached (NR)] <i>v</i> 3.0 months [2.7-13.6] hazard ratio, 0.48 [95% CI, 0.23 to 0.97], <i>P</i> = .018). Avelumab patients who crossed over (n = 9) to combination had a median PFS after crossover of 11.3 months (5.8-NR). The confirmed ORR was 27.6% with avelumab + cetuximab and 21.4% with avelumab. Grade 3 treatment-related adverse events occurred in 48.3% and 21.5% of patients with avelumab + cetuximab (most common: rash [20.7%], infusion reaction [20.7%]) and avelumab, respectively.</p><p><strong>Conclusion: </strong>Avelumab + cetuximab significantly improved PFS versus avelumab alone in patients with advanced cSCC. Alliance A091802 supports a larger confirmatory study with the combination of cetuximab and PD-1:PD-(L)1 blockade.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500759"},"PeriodicalIF":42.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191860","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":"Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study.","authors":"Hani M Babiker, Vincent Picozzi, Sreenivasa R Chandana, Bohuslav Melichar, Anup Kasi, Jin Gang, Javier Gallego, Andrea Bullock, Hao Chunyi, Lucjan Wyrwicz, Erika Hitre, Arsen Osipov, Christelle de la Fouchardiere, Inmaculada Ales, Tomislav Dragovich, Woojin Lee, Kynan Feeney, Philip Philip, Makoto Ueno, Eric Van Cutsem, Thomas Seufferlein, Teresa Macarulla","doi":"10.1200/JCO-25-00746","DOIUrl":"10.1200/JCO-25-00746","url":null,"abstract":"<p><strong>Purpose: </strong>Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC).</p><p><strong>Methods: </strong>In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m² and nab-paclitaxel 125 mg/m² by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc.</p><p><strong>Results: </strong>OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] <i>v</i> 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; <i>P</i> = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] <i>v</i> 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; <i>P</i> = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] <i>v</i> 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; <i>P</i> = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE.</p><p><strong>Conclusion: </strong>This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500746"},"PeriodicalIF":42.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191861","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":"Zanubrutinib and Venetoclax for Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With and Without Del(17p)/<i>TP53</i> Mutation: SEQUOIA Arm D Results.","authors":"Mazyar Shadman, Talha Munir, Shuo Ma, Masa Lasica, Monica Tani, Tadeusz Robak, Ian W Flinn, Jennifer R Brown, Paolo Ghia, Emmanuelle Ferrant, Constantine S Tam, Wojciech Janowski, Wojciech Jurczak, Linlin Xu, Tian Tian, Marcus Lefebure, Stephanie Agresti, Jamie Hirata, Alessandra Tedeschi","doi":"10.1200/JCO-25-00758","DOIUrl":"https://doi.org/10.1200/JCO-25-00758","url":null,"abstract":"<p><strong>Purpose: </strong>Several chronic lymphocytic leukemia (CLL) studies have demonstrated promising efficacy with the combination of BCL2 and Bruton tyrosine kinase inhibitors; however, patients with CLL with del(17p) and/or <i>TP53</i> mutation (<i>TP53</i>mut) comprised a small percentage of study populations or were excluded entirely. The purpose of the SEQUOIA Arm D cohort was to evaluate the combination of zanubrutinib + venetoclax in treatment-naïve (TN) patients with CLL/small lymphocytic lymphoma (SLL), in a large population of patients with <i>TP53</i>-aberrant disease.</p><p><strong>Patients and methods: </strong>Arm D is a nonrandomized cohort of patients aged 65 years and older (or 18-64 years with comorbidities). Patients received zanubrutinib from cycle 1 and venetoclax from cycle 4 (ramp-up) to cycle 28, followed by continuous zanubrutinib monotherapy until progressive disease (PD), unacceptable toxicity, or meeting undetectable minimal residual disease (uMRD)-guided stopping criteria.</p><p><strong>Results: </strong>Between November 2019 and July 2022, 114 patients were enrolled: 66 (58%) with <i>TP53</i>-aberrant disease, 47 (41%) without <i>TP53</i>-aberrant disease, and 1 with missing <i>TP53</i> results. At a median follow-up of 31.2 months, 85 patients (75%) remained on zanubrutinib monotherapy; 29 patients (25%) discontinued zanubrutinib because of adverse event, uMRD-guided stopping criteria, PD, or other. In the intention-to-treat population, 59% of patients achieved peripheral blood uMRD. The 24-month progression-free survival estimate was 92% (95% CI, 85% to 96%). The most common any-grade treatment-emergent AEs (TEAEs) were COVID-19 (54%), diarrhea (41%), contusion (32%), and nausea (30%). The most common grade ≥3 TEAEs were neutropenia (17%), hypertension (10%), diarrhea (6%), and decreased neutrophil count (6%).</p><p><strong>Conclusion: </strong>Zanubrutinib + venetoclax demonstrated impressive efficacy and a favorable safety profile in patients with TN CLL/SLL, regardless of the presence of <i>TP53</i>-aberrant disease.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500758"},"PeriodicalIF":42.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191863","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}