Journal of Clinical Oncology最新文献

{"title":"Isatuximab Subcutaneous by On-Body Delivery System vs Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase 3 IRAKLIA Study.","authors":"Sikander Ailawadhi, Ivan Špička, Andrew Spencer, Jin Lu, Albert Oriol, Silvia Ling, Fredrik Schjesvold, Alejandro Berkovits, Marek Hus, Chunrui Li, Meletios-Athanasios Dimopoulos, Péter Rajnics, Sevgi Kalayoğlu Beşışık, Vania Hungria, Maria Del Rosario Custidiano, Gurdeep Parmar, Xavier Leleu, Fei Li, Claudio Cerchione, Cesar Gomez, Tadao Ishida, Maria Victoria Mateos, Tondre T Buck, Richard LeBlanc, Jiří Minařík, Hartmut Goldschmidt, Rick Zhang, Dorothée Sémiond, Florence Suzan, Maya Stefanova-Urena, Victorine Koch, Philippe Moreau","doi":"10.1200/JCO-25-00744","DOIUrl":"https://doi.org/10.1200/JCO-25-00744","url":null,"abstract":"<p><strong>Purpose: </strong>To report results of the multicenter, open-label IRAKLIA trial (NCT05405166) of isatuximab subcutaneous (SC) versus intravenous (IV), plus pomalidomide and dexamethasone, in relapsed/refractory multiple myeloma (MM), the first Phase 3 MM trial using an on-body delivery system (OBDS).</p><p><strong>Methods: </strong>Patients with ≥1 prior line of therapy were randomized 1:1 to isatuximab OBDS (1400 mg) or IV (10 mg/kg) weekly in Cycle (C)1, then every 2 weeks, plus pomalidomide (4 mg/day, Day [D]1-21) and dexamethasone (40 mg weekly [age ≥75: 20 mg]) and treated until progression, unacceptable toxicity, or patient request. Co-primary endpoints were overall response rate (ORR; non-inferiority margin, 0.839) and isatuximab C_trough (C6D1 predose; non-inferiority margin, 0.8). Non-inferiority of OBDS versus IV was demonstrated if both co-primary endpoints achieved non-inferiority.</p><p><strong>Results: </strong>IRAKLIA randomized 531 patients (OBDS, n=263; IV, n=268). After 12 months median follow-up, ORR was 71.1% (OBDS) and 70.5% (IV; relative risk [95% CI]=1.008 [0.903-1.126]; lower CI exceeded non-inferiority margin). Mean (SD) C6D1 C_trough was 499 (259) μg/mL (OBDS) and 340 (169) μg/mL (IV). C_trough geometric mean ratio (90% CI) was 1.532 (1.316-1.784); lower CI exceeded non-inferiority margin. Grade ≥3 treatment-emergent adverse event incidences were 81.7% (OBDS) and 76.1% (IV); infusion reaction incidences were 1.5% and 25.0%. Injection site reactions occurred in 0.4% of OBDS injections (all grade 1-2); 99.9% of injections completed without interruption.</p><p><strong>Conclusion: </strong>IRAKLIA demonstrated efficacy and pharmacokinetic non-inferiority between isatuximab OBDS and IV. No unexpected safety signal was observed, with excellent local tolerability of isatuximab OBDS. Efficacy and safety were comparable to isatuximab IV in ICARIA-MM, except the lower OBDS infusion reaction rate. These results support potential use of the OBDS, designed to improve practice efficiency.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"101200JCO2500744"},"PeriodicalIF":42.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208662","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":"Long-term follow-up of real-world adjuvant anti-PD1 checkpoint inhibition and targeted therapy in stage III melanoma patients.","authors":"Georg C Lodde, Jessica C Hassel, Imke von Wasielewski, Friedegund Meier, Peter Mohr, Katharina Kähler, Axel Hauschild, Valerie Glutsch, Henner Stege, Carola Berking, Svea Hüning, Julia Huynh, Ralf Gutzmer, Lydia Reinhardt, Bastian Schilling, Carmen Loquai, Michael Erdmann, Andreas Stang, Bernd Kowall, Wolfgang Galetzka, Alexander Roesch, Daniel Tilkorn, Selma Ugurel, Lisa Zimmer, Dirk Schadendorf, Andrea Forschner, Elisabeth Livingstone","doi":"10.1200/JCO-24-02776","DOIUrl":"https://doi.org/10.1200/JCO-24-02776","url":null,"abstract":"<p><strong>Purpose: </strong>Adjuvant treatment with immune checkpoint inhibition (PD1) and targeted therapy (TT) with BRAF+MEK inhibitors significantly improved recurrence-free survival (RFS) of stage III melanoma patients. We investigated efficacy of adjuvant therapy with PD1 or TT under real-world conditions.</p><p><strong>Patients and methods: </strong>A total of 589 stage III melanoma patients who started adjuvant PD1 or TT between June 2018 and September 2019 from 11 major German Dermatologic Cooperative Oncology Group (DeCOG) skin cancer centers were followed for 4 years. Endpoints were RFS, overall (OS) and melanoma-specific survival (MSS). Survival analyses and adjusted hazard ratios (HRs) were estimated with Kaplan-Meier and Cox proportional hazards model, inverse probability treatment weighting and propensity score matching.</p><p><strong>Results: </strong>RFS at 48 months was 42.9% (95% CI 38.5-47.8) for all PD1 patients and 52.6% (95% CI 43.6-63.3) for TT patients. Among <i>BRAF</i>-mutated patients, rate of recurrence was higher for PD1 compared to TT (HR 1.57, 95% CI 1.09-2.26). OS at 4 years was 80.8% [95%CI 73.6-88.7] for <i>BRAF</i>-mutated PD1 patients and 87.3% [95%CI 81.0-94.0]) for TT patients. Patients starting adjuvant PD1 after resection of macroscopic lymph node metastases had a higher risk of rapid recurrence (1-year RFS all PD1 58%) compared to 87% in TT patients. Rate of recurrence after premature discontinuation (≤6 vs. >6 months treatment) was higher in TT patients (HR 1.47, 95% CI 0.67-3.23), but not in PD1 patients (HR 1.07, 95% CI 0.73-1.55).</p><p><strong>Conclusion: </strong><i>BRAF</i>-mutated PD1 patients had a markedly higher rate of relapse compared to TT patients. Rapid recurrences occured particulary in PD1-treated patients with prior macroscopic lymph node metastasis. Treatment duration shorter than 6 months did not negatively impact RFS in PD1, but in TT patients.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"101200JCO2402776"},"PeriodicalIF":42.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215969","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":"Long-term Efficacy and Safety of Lifileucel Tumor-infiltrating Lymphocyte (TIL) Cell Therapy in Patients with Advanced Melanoma: A 5-year Analysis of the C-144-01 Study.","authors":"Theresa Medina, Jason A Chesney, Harriet M Kluger, Omid Hamid, Eric D Whitman, Mike Cusnir, Sajeve S Thomas, Martin Wermke, Evidio Domingo-Musibay, Giao Q Phan, John M Kirkwood, James Larkin, Jeffrey Weber, Friedrich Graf Finckenstein, Jeffrey Chou, Brian Gastman, Xiao Wu, Rana Fiaz, Amod A Sarnaik","doi":"10.1200/JCO-25-00765","DOIUrl":"https://doi.org/10.1200/JCO-25-00765","url":null,"abstract":"<p><p>Patients with advanced melanoma resistant to immune checkpoint or BRAF/MEK inhibitors have treatment options with relatively low efficacy. Lifileucel, a one-time autologous tumor-infiltrating lymphocyte cell therapy, was approved in the US based on the pivotal C-144-01 study. A 5-year follow-up of the C-144-01 trial assessed the long-term efficacy and safety of lifileucel. At the cutoff date (November 20, 2024), the ORR was 31.4% (complete response [CR], 5.9%; partial response [PR], 25.5%). Overall, 79.3% of patients had tumor burden reduction; 16 had deepened responses with 4 converting from PR to CR > 1 year after lifileucel infusion; 31.3% of responders completed the 5-year assessment with ongoing responses. The median duration of response was 36.5 months. Responders (n = 48) had lower tumor burden and fewer liver or brain metastases than the overall population. Median overall survival (OS) was 13.9 months, with 5-year OS of 19.7%. Adverse events were consistent with nonmyeloablative lymphodepletion and interleukin-2 safety profiles and declined rapidly within 2 weeks after lifileucel infusion. Most grade 3/4 cytopenias resolved to grade ≤ 2 by day 30. This 5-year analysis demonstrated long-term benefit and meaningful OS with one-time lifileucel therapy, with no additional long-term safety concerns.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"101200JCO2500765"},"PeriodicalIF":42.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199178","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":"Retraction: Phase 1 Clinical Trial of EpCAM CAR-T Cell Therapy in Patients With Gastrointestinal Cancers.","authors":"","doi":"10.1200/JCO-25-01268","DOIUrl":"https://doi.org/10.1200/JCO-25-01268","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501268"},"PeriodicalIF":42.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199182","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":"Neoadjuvant Osimertinib for Resectable <i>EGFR</i>-Mutated Non-Small Cell Lung Cancer.","authors":"Jianxing He, Masahiro Tsuboi, Walter Weder, Ke-Neng Chen, Maximilian J Hochmair, Jin-Yuan Shih, Sung Yong Lee, Kang-Yun Lee, Nguyen Viet Nhung, Somcharoen Saeteng, Lunxu Liu, Ligang Xing, Nguyen Hoang Gia, Shuji Murakami, Yongtao Han, María Paz Saavedra, Seong Hoon Yoon, Carlos H A Teixeira, Carles Escriu, Alex Martinez-Marti, Collin M Blakely, Yasushi Yatabe, Sanja Dacic, Yuri Rukazenkov, Xiangning Huang, Anupriya Dayal, Jamie E Chaft","doi":"10.1200/JCO-25-00883","DOIUrl":"10.1200/JCO-25-00883","url":null,"abstract":"<p><strong>Purpose: </strong>Adjuvant osimertinib is the standard of care for patients with resected epidermal growth factor receptor (<i>EGFR</i>)-mutated non-small cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes.</p><p><strong>Methods: </strong>In this randomized, controlled, phase III study, patients with resectable, <i>EGFR</i>-mutated, stage II-IIIB NSCLC were randomly assigned (1:1:1) to receive neoadjuvant osimertinib (80 mg orally once daily for ≥9 weeks) plus platinum-based chemotherapy (once every 3 weeks for three cycles), osimertinib monotherapy (for ≥9 weeks), or placebo plus platinum-based chemotherapy (control), followed by surgical resection. Adjuvant osimertinib was offered to eligible patients after completion of surgery. The primary end point was major pathologic response (MPR) by blinded central pathology review. Event-free survival (EFS) was a secondary end point.</p><p><strong>Results: </strong>Overall, 358 patients were randomly assigned to receive osimertinib plus chemotherapy (121 patients), osimertinib monotherapy (117 patients), or placebo plus chemotherapy (120 patients). Osimertinib plus chemotherapy (MPR rate 26%) and osimertinib monotherapy (25%) demonstrated statistically significant improvement in the MPR rate versus placebo plus chemotherapy (2%), with corresponding odds ratios of 19.82 (95.002% CI, 4.60 to 85.33; <i>P</i> < .0001) and 19.28 (99.9% CI, 1.71 to 217.39; <i>P</i> < .0001), respectively. With 15% data maturity, the EFS rates at 12 months were 93%, 95%, and 83% with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. In the neoadjuvant period, grade ≥3 adverse events of any cause occurred in 36%, 13%, and 33% of patients with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. No new safety concerns were identified.</p><p><strong>Conclusion: </strong>Neoadjuvant osimertinib with or without chemotherapy demonstrated statistically significant improvement in the MPR rate over chemotherapy alone in patients with resectable, <i>EGFR</i>-mutated, stage II-IIIB NSCLC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2500883"},"PeriodicalIF":42.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199179","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":"Neoadjuvant Osimertinib: A Step Ahead or Just a Step?","authors":"Suresh S Ramalingam, Thomas E Stinchcombe","doi":"10.1200/JCO-25-01020","DOIUrl":"https://doi.org/10.1200/JCO-25-01020","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501020"},"PeriodicalIF":42.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199180","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: Mid-Treatment Positron Emission Tomography-Adaptive Radiotherapy in Stage III Non-Small Cell Lung Cancer: Another Attempt Toward Personalized Care.","authors":"Feng-Ming Spring Kong, Chen Hu, Jeffrey D Bradley, Mitchell Machtay","doi":"10.1200/JCO-25-00069","DOIUrl":"10.1200/JCO-25-00069","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1936-1937"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674011","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":"Maintenance Chemotherapy in Patients With High-Risk Rhabdomyosarcoma: Long-Term Survival Analysis of the European <i>Paediatric</i> Soft Tissue Sarcoma Study Group RMS 2005 Trial.","authors":"Gianni Bisogno, Julia Chisholm, Raquel Hladun, Gian Luca De Salvo, Florent Guerin, Michela Casanova, Henry Mandeville, Rita Alaggio, Beatrice Coppadoro, Daniel Orbach, Andrea Ferrari, Rick van Rijn, Anne-Sophie Defachelles, Myriam Ben-Arush, Heidi Glosli, Maja Cesen, Johannes H M Merks, Véronique Minard-Colin","doi":"10.1200/JCO-24-02850","DOIUrl":"10.1200/JCO-24-02850","url":null,"abstract":"<p><p>The European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 trial evaluated maintenance chemotherapy in high-risk rhabdomyosarcoma (RMS). Patients were randomly assigned to either discontinue treatment (standard arm) or receive six 28-day cycles of vinorelbine (25 mg/m²) once per day on days 1, 8, and 15, plus once daily low-dose cyclophosphamide (25 mg/m²; experimental arm). Initial results showed improved overall survival (OS), but disease-free survival (DFS) improvement was not statistically significant. This report presents mature survival outcomes after extended follow-up. Between April 2006 and December 2016, 186 patients were enrolled in the standard arm and 185 in the experimental arm. After a median follow-up of 122.1 months from diagnosis and 114 months from random assignment, recurrence, progression, or death occurred in 103 patients (61 standard arm, 42 experimental arm). The 10-year DFS was 66.5% (95% CI, 59 to 74) in the standard arm versus 77.1% (95% CI, 70.3 to 82.5) in the experimental arm (<i>P</i> = .025). Corresponding 10-year OS rates were 70.8% (95% CI, 63.3 to 77.0) and 82.9% (95% CI, 76.6 to 87.7; <i>P</i> = .0099). Long-term results of the RMS2005 trial confirm the survival benefit of maintenance chemotherapy with vinorelbine and low-dose cyclophosphamide for patients with high-risk RMS.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1856-1862"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575567","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":"Taletrectinib in <i>ROS1</i>+ Non-Small Cell Lung Cancer: TRUST.","authors":"Maurice Pérol, Wei Li, Nathan A Pennell, Geoffrey Liu, Yuichiro Ohe, Filippo De Braud, Misako Nagasaka, Enriqueta Felip, Anwen Xiong, Yongchang Zhang, Huijie Fan, Xicheng Wang, Shuanglian Li, Rose K Lai, Feiwu Ran, Xianyu Zhang, Wenfeng Chen, Lyudmila Bazhenova, Caicun Zhou","doi":"10.1200/JCO-25-00275","DOIUrl":"10.1200/JCO-25-00275","url":null,"abstract":"<p><strong>Purpose: </strong>Taletrectinib is an oral, potent, CNS-active, selective, next-generation ROS1 tyrosine kinase inhibitor (TKI). We report integrated efficacy and safety from registrational taletrectinib studies in <i>ROS1</i>+ non-small cell lung cancer.</p><p><strong>Methods: </strong>TRUST-I and TRUST-II were phase II, single-arm, open-label, nonrandomized, multicenter trials. Efficacy outcomes were pooled from TRUST-I and TRUST-II pivotal cohorts. The safety population comprised all patients treated with once-daily oral taletrectinib 600 mg pooled across the taletrectinib clinical program. The primary end point was independent review committee-assessed confirmed objective response rate (cORR). Secondary outcomes included intracranial (IC)-ORR, progression-free survival (PFS), duration of response (DOR), and safety.</p><p><strong>Results: </strong>As of June 7, 2024, the efficacy-evaluable population included 273 patients in TRUST-I and TRUST-II. Among TKI-naïve patients (n = 160), the cORR was 88.8% and the IC-cORR was 76.5%; in TKI-pretreated patients (n = 113), the cORR was 55.8% and the IC-cORR was 65.6%. In TKI-naïve patients, the median DOR and median PFS were 44.2 and 45.6 months, respectively. In TKI-pretreated patients, the median DOR and median PFS were 16.6 and 9.7 months. The cORR in patients with G2032R mutation was 61.5% (8 of 13). Among 352 patients treated with taletrectinib 600 mg once daily, the most frequent treatment-emergent adverse events (TEAEs) were GI events (88%) and elevated AST (72%) and ALT (68%); most were grade 1. Neurologic TEAEs were infrequent (dizziness, 21%; dysgeusia, 15%) and mostly grade 1. TEAEs leading to discontinuations (6.5%) were low.</p><p><strong>Conclusion: </strong>Taletrectinib showed a high response rate with durable responses, robust IC activity, prolonged PFS, favorable safety, and low rates of neurologic adverse events in TKI-naïve and pretreated patients.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1920-1929"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine Therapy Omission in Estrogen Receptor-Low (1%-10%) Early-Stage Breast Cancer.","authors":"Grace M Choong, Tanya L Hoskin, Judy C Boughey, James N Ingle, Matthew P Goetz","doi":"10.1200/JCO-24-02263","DOIUrl":"10.1200/JCO-24-02263","url":null,"abstract":"<p><strong>Purpose: </strong>Adjuvant endocrine therapy (ET) improves overall survival (OS) in estrogen receptor (ER)-positive early-stage breast cancer (BC). However, the benefit of ET for those with ER-low BC (ER 1%-10%) is unclear.</p><p><strong>Methods: </strong>Using the National Cancer Database, we studied patients with high-risk stage I to III, ER-low BC (defined as immunohistochemistry 1%-10%) who received (neo)adjuvant chemotherapy and did or did not initiate ET. OS was analyzed with ET initiation as a time-dependent covariate using Cox proportional hazards regression.</p><p><strong>Results: </strong>Of 10,362 patients with stage I to III ER-low BC, 7,018 received chemotherapy and met inclusion criteria. ET omission was 42% at 12 months and more common in patients with tumors that were progesterone receptor-negative, human epidermal growth factor receptor 2-negative, higher-grade (grade 2/3) and higher Ki-67 (≥20%; all <i>P</i> < .001) and those who received neoadjuvant chemotherapy (NAC; <i>P</i> < .001). With a median follow-up of 3 years, 586 deaths were observed. In a multivariable analysis, ET omission was associated with a higher risk of death (hazard ratio [HR], 1.23 [95% CI, 1.04 to 1.46]; <i>P</i> = .02), with a greater impact in those with higher ER levels: ER 1%-5% (HR, 1.15 [95% CI, 0.91 to 1.45]; <i>P</i> = .24) versus ER 6%-10% (HR, 1.42 [95% CI, 1.00 to 2.02]; <i>P</i> = .048). Among patients treated with NAC (n = 4,377, 62%), ET omission was associated with worse OS in those with residual disease (RD; HR, 1.26 [95% CI, 1.00 to 1.57]; <i>P</i> = .046) but not in those who achieved a pathologic complete response (HR, 1.06 [95% CI, 0.62 to 1.80]; <i>P</i> = .84).</p><p><strong>Conclusion: </strong>In ER-low, early-stage BC, ET omission is associated with significantly worse OS, especially in patients with RD after NAC and those with higher (6%-10%) ER levels. Until prospective data are available, patients with ER-low BC should be counseled regarding the potential benefit of ET.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"1875-1885"},"PeriodicalIF":42.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}