Annals of Oncology最新文献

英文中文

From algorithms to meaningful biomarkers: anchoring AI in clinical oncology 从算法到有意义的生物标志物：将人工智能锚定在临床肿瘤学中。

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-13 DOI: 10.1016/j.annonc.2026.01.002

E.G.E. de Vries , E. Garralda , S. Litière

引用次数: 0

Is there a future for Trop-2-targeted ADCs in urothelial carcinoma? trop -2靶向adc治疗尿路上皮癌有前景吗？

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2026-02-12 DOI: 10.1016/j.annonc.2026.01.007

S. Coca Membribes, T. Powles

引用次数: 0

Sacituzumab tirumotecan in participants with advanced or metastatic urothelial carcinoma and disease progression after chemotherapy and immune checkpoint inhibitors 舒妥珠单抗替鲁莫替康在化疗和免疫检查点抑制剂后晚期或转移性尿路上皮癌和疾病进展患者中的应用

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2025-11-21 DOI: 10.1016/j.annonc.2025.11.013

Y. Zhu , S. Jiang , Y. Shi , S. Wang , F. Yuan , F. Zhou , K. Jiang , X. Zhang , L. Seneviratne , G. Yu , M. Zhang , T. Liu , X. Li , X. Chen , X. Wang , S. Zhang , Y. Liu , Y. Ge , M. Chen , G. Blumenthal , D. Ye

Background

Trophoblast cell-surface antigen 2 (TROP2) is overexpressed in advanced or metastatic urothelial cancer (UC), representing a promising therapeutic target. Sacituzumab tirumotecan (sac-TMT) is a TROP2-directed antibody-drug conjugate with a unique, bifunctional linker that maximizes payload delivery to tumor cells. We present preliminary results for sac-TMT monotherapy from cohort 9 of the phase 1/2 2870-001/KL264-01 study in participants with advanced or metastatic UC.

Participants and methods

Eligible participants with locally advanced or metastatic UC and disease progression on one or more prior line of platinum-based chemotherapy and anti–programmed cell death protein 1/programmed cell death-ligand 1 therapy received sac-TMT 5 mg/kg intravenously every 2 weeks until disease progression, unacceptable toxicity, or participant/physician decision. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST version 1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results

By data cut-off (17 February 2025), 49 participants were treated with sac-TMT; 37 (76%) had received two or more prior lines of therapy. Median follow-up for this analysis was 18.8 months. The confirmed ORR was 31% [95% confidence interval (CI), 18% to 45%] and the disease control rate was 71% (95% CI 57% to 83%). Median DOR was not reached [range 2.1-22.2+ (+ indicates censored data for the longest DOR, suggesting that patients may have achieved longer remission duration) months], and the 12-month probability of sustained response was 53%. Median PFS and OS were 5.5 months (95% CI 3.6-7.2 months) and 12.1 months (95% CI, 9.9-15.3 months), with 18-month rates of 26% and 33%, respectively. Grade 3/4 treatment-related adverse events (AEs) occurred in 31 participants (63%), and the most common (≥5%) were anemia (41%), decreased neutrophil count (35%), decreased white blood cell count (20%), stomatitis (12%), and decreased platelet count (8%). There were no grade 5 treatment-related AEs or febrile neutropenia events.

Conclusions

Sac-TMT 5 mg/kg monotherapy every 2 weeks demonstrated promising antitumor activity in participants with heavily pretreated advanced or metastatic UC, with a manageable safety profile, warranting further evaluation of sac-TMT in this population.

背景：滋养细胞表面抗原2 （TROP2）在晚期或转移性尿路上皮癌（UC）中过表达，是一个有希望的治疗靶点。Sacituzumab替鲁莫替康（Sacituzumab tirumotecan, sact - tmt）是一种trop2导向的抗体-药物偶联物，具有独特的双功能连接物，可最大限度地将有效载荷递送到肿瘤细胞。我们报告了来自1/2期2870-001/KL264-01研究9队列中晚期或转移性UC患者的sacc - tmt单药治疗的初步结果。参与者和方法：符合条件的局部晚期或转移性UC和疾病进展≥1条既往铂基化疗和抗pd -(L)1治疗的参与者每2周静脉注射5mg /kg的sactmt，直到疾病进展、不可接受的毒性或参与者/医生决定。主要终点是研究者根据RECIST 1.1版评估的客观缓解率（ORR）。次要终点包括反应持续时间（DOR）、无进展生存期（PFS）、总生存期（OS）和安全性。结果：截至数据截止（2025年2月17日），49名参与者接受了sac-TMT治疗；37例（76%）患者既往接受过≥2条治疗线。该分析的中位随访时间为18.8个月。确诊ORR为31% (95% CI, 18%-45%)，疾病控制率为71% （95% CI, 57%-83%）。中位DOR未达到（范围，2.1-22.2 +个月），12个月持续缓解的概率为53%。中位PFS和OS分别为5.5 （95% CI, 3.6-7.2）个月和12.1 （95% CI, 9.9-15.3）个月，18个月生存率分别为26%和33%。31名参与者（63%）发生了3/4级治疗相关不良事件（ae），最常见的（≥5%）是贫血（41%）、中性粒细胞计数减少（35%）、白细胞计数减少（20%）、口炎（12%）和血小板计数减少（8%）。没有5级治疗相关不良事件或发热性中性粒细胞减少事件。结论：Sac-TMT每2周5 mg/kg单药治疗在重度预处理的晚期或转移性UC患者中显示出有希望的抗肿瘤活性，具有可管理的安全性，需要进一步评估Sac-TMT在该人群中的应用。

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引用次数: 0

Early positron emission tomography response-adapted treatment in low-risk diffuse large B-cell lymphoma: an open-label, multicenter, randomized, noninferiority phase III trial☆ 低风险弥漫性大b细胞淋巴瘤的早期正电子发射断层扫描反应适应治疗：一项开放标签、多中心、随机、非劣效性的3期试验

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2025-11-17 DOI: 10.1016/j.annonc.2025.11.006

J.-M. Michot , S. Bologna , J.-N. Bastie , T.V. Borght , J. Brière , V. Ribrag , C. Bommier , F. Peyrade , L. Lebras , G. Damaj , D. Coso , D. Sibon , C. Bonnet , F. Morschhauser , H. Ghesquières , C. Fruchart , C. Soussain , S. Becker , P. Olivier , A. Julian , H. Tilly

Background

Preliminary reports suggest interim positron emission tomography (PET) could drive treatment duration in limited-stage diffuse large B-cell lymphoma (DLBCL). This phase III randomized study in first-line therapy for DLBCL patients with adjusted-age international prognostic index (aaIPI) risk = 0, evaluates an experimental PET-response adapted approach using PET response after two cycles of R-CHOP to de-escalate treatment duration.

Patients and methods

LNH2009-1B study is a two-arm, open-label, multicenter, prospective, randomized phase III noninferiority trial, evaluating treatment de-escalation based on PET after two cycles of R-CHOP in previously untreated DLBCL patients aged 18-80 years, with aaIPI = 0. In the experimental PET-adapted arm, patients with a negative PET after two cycles received four cycles in total of R-CHOP, whereas those with a positive PET after two cycles received a total of six cycles. In the standard arm, treatment was six cycles regardless of PET results after two cycles. No radiotherapy was planned. The primary endpoint was 3 years progression-free survival (PFS). The primary analysis was carried out in the intention-to-treat population. The trial is registered with ClinicalTrial.gov, NCT 01285765, recruitment is completed.

Results

A total of 650 patients were enrolled, of whom 319 were randomly assigned to the PET-adapted arm and 331 to the standard arm. In the PET-adapted arm, 77.7% of patients had a negative PET scan after two cycles and received a total of four cycles of R-CHOP. The 3-year PFS in PET-adapted and standard arms were 92.0% [95% confidence interval (CI) 88.3% to 94.5%] and 89.2% (95% CI 85.3% to 92.2%), respectively (P value = 0.070). The noninferiority of the experimental PET-adapted arm was demonstrated (hazard ratio 0.72, 95% CI 0.47-1.12, P value < 0.0001). Patients in the PET-adapted arm had fewer adverse events of grades ≥3 (54.7% versus 62.7%, P = 0.046) and serious adverse events (9.5% versus 14.2%, P = 0.039).

Conclusion

A risk-adapted approach using early PET after two cycles of R-CHOP was beneficial, minimizing toxicity without compromising efficacy in patients treated in first-line therapy for low-risk DLBCL.

背景：初步报告表明，中期正电子发射断层扫描（PET）可以延长有限期弥漫性大b细胞淋巴瘤（DLBCL）的治疗时间。这项针对调整年龄IPI （aaIPI）风险= 0的DLBCL患者一线治疗的3期随机研究，评估了一种实验性PET反应适应方法，在2个周期的R-CHOP后使用PET反应来缩短治疗时间。方法：LNH2009-1B研究是一项两组、开放标签、多中心、前瞻性、随机3期非效性试验，评估18-80岁未治疗的DLBCL患者在接受2个周期R-CHOP治疗后基于PET的治疗降级，aaIPI =0。在实验PET适应组中，2个周期后PET阴性的患者共接受4个周期的R-CHOP，而2个周期后PET阳性的患者共接受6个周期的R-CHOP。在标准组中，不论2个周期后的PET结果如何，治疗为6个周期。未计划放疗。主要终点是3年无进展生存（PFS）。初步分析是在意向治疗人群中进行的。该试验已在ClinicalTrial.gov注册，编号NCT01285765，招募已完成。结果：650例患者入组，其中319例随机分配到pet适应组，331例随机分配到标准组。在PET适应组中，77.7%的患者在2个周期后PET阴性，共接受4个周期或R-CHOP治疗。pet适应组和标准组的3年PFS分别为92.0% （95% CI 88.3-94.5）和89.2% (95% CI 85.3-92.2) （p值=0.070）。实验证实了PET适应组的非劣效性（风险比0.72,95% CI: 0.47-1.12， p值）。结论：对于低风险DLBCL的一线治疗患者，在2个R-CHOP周期后使用早期PET的风险适应方法有利于最小化毒性而不影响疗效。

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引用次数: 0

Intercepting endocrine resistance in ER-positive/HER2-negative metastatic breast cancer: insights from the PADA-1 trial 阻断ER+/HER2转移性乳腺癌的内分泌抵抗：来自PADA-1试验的见解

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2025-11-15 DOI: 10.1016/j.annonc.2025.11.003

D.S. Guttery , J.A. Shaw , J. Stebbing

引用次数: 0

Emerging options and future strategies in immunotherapy for advanced lung squamous-cell carcinoma 晚期肺鳞状细胞癌免疫治疗的新选择和未来策略。

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2025-11-17 DOI: 10.1016/j.annonc.2025.11.008

Y. Wang , R. Rosell , F.R. Hirsch , S. Lu , R. Govindan , K. Park , S. Peters , J.J. Zhang

Advanced-stage lung squamous-cell carcinoma (LUSC) remains a therapeutic challenge. Although immune checkpoint inhibitors (ICIs) have revolutionized LUSC treatment, only a small subset of LUSC patients can achieve durable clinical benefits, underscoring the need for novel strategies. Emerging immunotherapy strategies have demonstrated early evidence of promise for LUSC patients, particularly multi-specific antibodies and fusion proteins, antibody-drug conjugates, adoptive cell therapies, and cancer vaccines. Additionally, advances in multi-omics and artificial intelligence offer potential for precise immunotherapy by deciphering the complex tumor-immune microenvironment and predicting therapeutic responses. The future of LUSC treatment lies in rational multi-target and biological therapies to boost immune cytotoxicity, as well as innovative technologies to refine patient selection. This review highlights the evolving landscape and outlines a roadmap for next-generation immunotherapies in LUSC.

晚期肺鳞状细胞癌（LUSC）仍然是一个治疗挑战。尽管免疫检查点抑制剂（ICIs）已经彻底改变了LUSC治疗，但只有一小部分LUSC患者可以获得持久的临床益处，这强调了对新策略的需求。新兴的免疫治疗策略已经显示出对LUSC患者有希望的早期证据，特别是多特异性抗体和融合蛋白、抗体-药物偶联物、过继细胞疗法和癌症疫苗。此外，多组学和人工智能的进步通过破译复杂的肿瘤免疫微环境和预测治疗反应，为精确免疫治疗提供了潜力。LUSC治疗的未来在于合理的多靶点和生物疗法来增强免疫细胞毒性，以及创新技术来优化患者选择。这篇综述强调了LUSC的发展前景，并概述了下一代免疫疗法的路线图。

引用次数: 0

To PET or not to PET, that is the question PET还是不PET，这是一个问题

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2026-02-12 DOI: 10.1016/j.annonc.2026.01.008

R. Suzuki

引用次数: 0

Repertoire and clinical hierarchy of AR locus alterations in castration-resistant prostate cancer 去势抵抗性前列腺癌中AR位点改变的范围和临床分级。

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2025-10-27 DOI: 10.1016/j.annonc.2025.10.1236

T. Virtanen , E.M. Kwan , K. Parekh , J.V.W. Bacon , C.F. Huang , I.P.L. Yu , L. Ryyppö , C.Q. Bernales , G. Donnellan , C. Tam , J. Sipola , J. Nikkola , G. Vandekerkhove , S.H. Tolmeijer , K. Kukkonen , Adelia , B.J. Eigl , D. Finch , R. Gagnon , Y. Takieldeen , A.W. Wyatt

Background

Somatic alterations to the androgen receptor (AR) gene are pivotal drivers of treatment resistance in metastatic castration-resistant prostate cancer (mCRPC), but their prevalence, clinical impact, and etiology remain incompletely understood.

Patients and methods

We assembled a meta-cohort of 3048 plasma cell-free DNA and matched leukocyte DNA samples from 1751 mCRPC patients, accrued from eight clinical trials and a regional biobank. Samples were sequenced with successive generations of a custom targeted hybridization capture panel with extensive coverage of the AR locus and 71 prostate cancer genes, enabling comprehensive characterization of AR genotypes including enhancer and gene copy number amplification, and mutations or structural rearrangements.

Results

Somatic AR alterations, detected in 84% of mCRPC, were shaped by underlying genomics, including TP53 and DNA repair defects. Wnt-mutant tumors showed unique AR amplification structures characterized by preferential incorporation of an alternative downstream enhancer and low copy number. AR mutations were present in 19.7% of mCRPC, often subclonal, and enriched in tumors with AR enhancer-only gain. We establish a functional hierarchy of AR genotypes based on treatment responses and identify a specific class of AR rearrangements truncating the ligand-binding domain within intron 4 or exon 4 (ALTR4) that are under robust positive selection and strongly impact AR pathway inhibitor outcomes, distinct from other rearrangements arising as byproducts of AR amplification. We provide evidence that a subset of AR amplifications arise through breakage-fusion-bridge cycles with associated Xq loss. Some 16% of mCRPC lacked detectable AR alterations and had reduced frequency of ETS gene fusions, with many demonstrating robust responses to AR pathway inhibitors.

Conclusions

This study provides the most comprehensive resource to date characterizing somatic alterations at the AR locus. Our clinicogenomic analysis establishes the repertoire and clinical relevance of AR genotypes in mCRPC, informing efforts to target renewed AR dependency.

背景：雄激素受体（AR）基因的体细胞改变是转移性去势抵抗性前列腺癌（mCRPC）治疗耐药的关键驱动因素，但其患病率、临床影响和病因尚不完全清楚。患者和方法：我们收集了来自8项临床试验和一个地区生物库的1751例mCRPC患者的3048例无浆细胞DNA和匹配的白细胞DNA样本的荟萃队列。对样品进行连续几代的定制靶向杂交捕获面板，广泛覆盖AR位点和71个前列腺癌基因，从而全面表征AR基因型，包括增强子和基因拷贝数扩增，突变或结构重排。结果：在84%的mCRPC中检测到的体细胞AR改变是由潜在的基因组学塑造的，包括TP53和DNA修复缺陷。wnt突变肿瘤表现出独特的AR扩增结构，其特点是优先结合另一种下游增强子和低拷贝数。AR突变存在于19.7%的mCRPC中，通常是亚克隆的，并且在仅具有AR增强子增益的肿瘤中富集。我们根据治疗反应建立了AR基因型的功能层次，并确定了截断内含子4或外显子4 （ALTR4）内配体结合域的AR重排的特定类别，这些重排处于强大的正选择下，并强烈影响AR途径抑制剂的结果，与AR扩增的副产物产生的其他重排不同。我们提供的证据表明，AR放大的一个子集是通过与Xq损失相关的断接-融合桥循环产生的。16%的mCRPC缺乏可检测的AR改变，并且ETS基因融合频率降低，其中许多对AR途径抑制剂表现出强烈的反应。结论：这项研究提供了迄今为止最全面的资源来表征AR位点的体细胞改变。我们的临床基因组学分析建立了mCRPC中AR基因型的库和临床相关性，为针对新的AR依赖提供了信息。

{"title":"Repertoire and clinical hierarchy of AR locus alterations in castration-resistant prostate cancer","authors":"T. Virtanen , E.M. Kwan , K. Parekh , J.V.W. Bacon , C.F. Huang , I.P.L. Yu , L. Ryyppö , C.Q. Bernales , G. Donnellan , C. Tam , J. Sipola , J. Nikkola , G. Vandekerkhove , S.H. Tolmeijer , K. Kukkonen , Adelia , B.J. Eigl , D. Finch , R. Gagnon , Y. Takieldeen , A.W. Wyatt","doi":"10.1016/j.annonc.2025.10.1236","DOIUrl":"10.1016/j.annonc.2025.10.1236","url":null,"abstract":"<div><h3>Background</h3><div>Somatic alterations to the androgen receptor (<em>AR</em>) gene are pivotal drivers of treatment resistance in metastatic castration-resistant prostate cancer (mCRPC), but their prevalence, clinical impact, and etiology remain incompletely understood.</div></div><div><h3>Patients and methods</h3><div>We assembled a meta-cohort of 3048 plasma cell-free DNA and matched leukocyte DNA samples from 1751 mCRPC patients, accrued from eight clinical trials and a regional biobank. Samples were sequenced with successive generations of a custom targeted hybridization capture panel with extensive coverage of the <em>AR</em> locus and 71 prostate cancer genes, enabling comprehensive characterization of <em>AR</em> genotypes including enhancer and gene copy number amplification, and mutations or structural rearrangements.</div></div><div><h3>Results</h3><div>Somatic AR alterations, detected in 84% of mCRPC, were shaped by underlying genomics, including <em>TP53</em> and DNA repair defects. Wnt-mutant tumors showed unique <em>AR</em> amplification structures characterized by preferential incorporation of an alternative downstream enhancer and low copy number. <em>AR</em> mutations were present in 19.7% of mCRPC, often subclonal, and enriched in tumors with <em>AR</em> enhancer-only gain. We establish a functional hierarchy of <em>AR</em> genotypes based on treatment responses and identify a specific class of <em>AR</em> rearrangements truncating the ligand-binding domain within intron 4 or exon 4 (ALTR4) that are under robust positive selection and strongly impact <em>AR</em> pathway inhibitor outcomes, distinct from other rearrangements arising as byproducts of <em>AR</em> amplification. We provide evidence that a subset of <em>AR</em> amplifications arise through breakage-fusion-bridge cycles with associated Xq loss. Some 16% of mCRPC lacked detectable <em>AR</em> alterations and had reduced frequency of ETS gene fusions, with many demonstrating robust responses to AR pathway inhibitors.</div></div><div><h3>Conclusions</h3><div>This study provides the most comprehensive resource to date characterizing somatic alterations at the <em>AR</em> locus. Our clinicogenomic analysis establishes the repertoire and clinical relevance of <em>AR</em> genotypes in mCRPC, informing efforts to target renewed AR dependency.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 3","pages":"Pages 388-402"},"PeriodicalIF":65.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399857","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}

引用次数: 0

Pooled analysis by best confirmed response to trastuzumab deruxtecan and related biomarkers in patients with HER2-positive metastatic breast cancer from DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03 DESTINY-Breast01、DESTINY-Breast02和DESTINY-Breast03 her2阳性转移性乳腺癌患者对曲妥珠单抗德鲁德康和相关生物标志物的最佳确认反应的汇总分析

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2025-11-18 DOI: 10.1016/j.annonc.2025.11.007

C. Saura , J. Cortés , S. Modi , S.-B. Kim , E. Hamilton , S.A. Hurvitz , I.E. Krop , G. Curigliano , H. Iwata , S.-A. Im , P. Herbolsheimer , M. Karnoub , A. Boran , Y. Kuwahara , A. Egorov , F. André

Background

Objective response rates in the DESTINY-Breast01/02/03 trials, which evaluated trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC), were 62%/70%/79%, respectively.

Patients and methods

This exploratory pooled analysis investigated associations between best confirmed response to T-DXd and baseline characteristics/long-term outcomes in patients who received T-DXd 5.4 mg/kg in DESTINY-Breast01/02/03. Endpoints included best confirmed response per (blinded) independent central review [(B)ICR] using RECIST v1.1, progression-free survival (PFS) by (B)ICR, overall survival (OS), safety, and biomarker analyses of expression levels/alterations of genes relevant to HER2-positive mBC or T-DXd activity.

Results

A total of 834 patients who received T-DXd in DESTINY-Breast01/02/03 were assessable for response; 125 (15.0%) experienced complete response (CR), 477 (57.2%) experienced partial response (PR), and 232 (27.8%) were considered non-responders (stable disease/progressive disease). The median number of prior regimens in the metastatic setting was two for patients with CR versus three for patients with PR and non-responders; visceral disease and baseline brain or bone metastases were less frequently observed in patients with CR. The 24-month PFS rates in patients with CR, PR, and no response, respectively, were 77.8%, 46.3%, and 20.6%, and 36-month OS rates were 88.6%, 54.0%, and 35.9%. Rates of serious adverse events, T-DXd discontinuation, and interstitial lung disease/pneumonitis were numerically lower in patients with CR. In exploratory biomarker analyses, responders had tumors with numerically higher HER2 plasma copy number, lower ESR1 gene expression and ESR1 mutation frequency, and lower circulating tumor DNA levels at baseline.

Conclusions

Patients with objective response to T-DXd, particularly those with CR, showed prolonged median PFS and OS. These results support T-DXd use across broad patient groups with HER2-positive mBC, including those with lower disease burden. Patients whose disease does not respond to T-DXd represent an unmet medical need, and research into more effective treatment approaches for these patients is warranted.

背景：destiny - breast1/02/03试验评估了曲妥珠单抗德鲁西替康（T-DXd）治疗人表皮生长因子受体2 （HER2）阳性转移性乳腺癌（mBC）的客观缓解率分别为62%/70%/79%。患者和方法：这项探索性合并分析调查了在destiny - breast中接受5.4 mg/kg T-DXd治疗的患者对T-DXd的最佳确认反应与基线特征/长期结局之间的关系。终点包括使用RECIST v1.1进行的（盲法）独立中心回顾（[B]ICR）的最佳确认疗效，(B)ICR的无进展生存期（PFS），总生存期（OS），安全性和与her2阳性mBC或T-DXd活性相关的基因表达水平/改变的生物标志物分析。结果：01/02/03在destiny - breast中接受T-DXd治疗的834例患者可评价疗效；125例（15.0%）出现完全缓解（CR）， 477例（57.2%）出现部分缓解（PR）， 232例（27.8%）被认为无反应（疾病稳定/疾病进展）。在转移性情况下，CR患者既往方案的中位数为2，PR和无反应患者为3；在CR患者中，内脏疾病和基线脑或骨转移的发生率较低。CR、PR和无反应患者的24个月PFS分别为77.8%、46.3%和20.6%，36个月OS分别为88.6%、54.0%和35.9%。在CR患者中，严重不良事件、T-DXd停药和间质性肺病/肺炎的发生率较低。在探索性生物标志物分析中，应答者的肿瘤具有较高的HER2血浆拷贝数、较低的ESR1基因表达和ESR1突变频率，以及较低的基线循环肿瘤DNA水平。结论：对T-DXd有客观反应的患者，特别是CR患者，中位PFS和OS延长。这些结果支持在her2阳性mBC的广泛患者群体中使用T-DXd，包括那些疾病负担较低的患者。对T-DXd无反应的患者代表着未满足的医疗需求，研究这些患者更有效的治疗方法是有必要的。

{"title":"Pooled analysis by best confirmed response to trastuzumab deruxtecan and related biomarkers in patients with HER2-positive metastatic breast cancer from DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03","authors":"C. Saura , J. Cortés , S. Modi , S.-B. Kim , E. Hamilton , S.A. Hurvitz , I.E. Krop , G. Curigliano , H. Iwata , S.-A. Im , P. Herbolsheimer , M. Karnoub , A. Boran , Y. Kuwahara , A. Egorov , F. André","doi":"10.1016/j.annonc.2025.11.007","DOIUrl":"10.1016/j.annonc.2025.11.007","url":null,"abstract":"<div><h3>Background</h3><div>Objective response rates in the DESTINY-Breast01/02/03 trials, which evaluated trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC), were 62%/70%/79%, respectively.</div></div><div><h3>Patients and methods</h3><div>This exploratory pooled analysis investigated associations between best confirmed response to T-DXd and baseline characteristics/long-term outcomes in patients who received T-DXd 5.4 mg/kg in DESTINY-Breast01/02/03. Endpoints included best confirmed response per (blinded) independent central review [(B)ICR] using RECIST v1.1, progression-free survival (PFS) by (B)ICR, overall survival (OS), safety, and biomarker analyses of expression levels/alterations of genes relevant to HER2-positive mBC or T-DXd activity.</div></div><div><h3>Results</h3><div>A total of 834 patients who received T-DXd in DESTINY-Breast01/02/03 were assessable for response; 125 (15.0%) experienced complete response (CR), 477 (57.2%) experienced partial response (PR), and 232 (27.8%) were considered non-responders (stable disease/progressive disease). The median number of prior regimens in the metastatic setting was two for patients with CR versus three for patients with PR and non-responders; visceral disease and baseline brain or bone metastases were less frequently observed in patients with CR. The 24-month PFS rates in patients with CR, PR, and no response, respectively, were 77.8%, 46.3%, and 20.6%, and 36-month OS rates were 88.6%, 54.0%, and 35.9%. Rates of serious adverse events, T-DXd discontinuation, and interstitial lung disease/pneumonitis were numerically lower in patients with CR. In exploratory biomarker analyses, responders had tumors with numerically higher <em>HER2</em> plasma copy number, lower <em>ESR1</em> gene expression and <em>ESR1</em> mutation frequency, and lower circulating tumor DNA levels at baseline.</div></div><div><h3>Conclusions</h3><div>Patients with objective response to T-DXd, particularly those with CR, showed prolonged median PFS and OS. These results support T-DXd use across broad patient groups with HER2-positive mBC, including those with lower disease burden. Patients whose disease does not respond to T-DXd represent an unmet medical need, and research into more effective treatment approaches for these patients is warranted.</div></div>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":"37 3","pages":"Pages 353-363"},"PeriodicalIF":65.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556106","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}

引用次数: 0

Standardizing time-to-event reporting in single-arm BCG-unresponsive registration trials: a case for Kaplan–Meier 单臂bcg无反应注册试验中标准化事件时间报告：Kaplan-Meier案例。

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology

Pub Date : 2026-03-01 Epub Date: 2025-11-24 DOI: 10.1016/j.annonc.2025.11.010

S.M. Monda , J.J. Meeks , T. Powles , T.M. Morgan

引用次数: 0

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