Nature Medicine最新文献

{"title":"Countering the impact of the climate crisis on health will require data","authors":"","doi":"10.1038/s41591-024-03276-0","DOIUrl":"10.1038/s41591-024-03276-0","url":null,"abstract":"As drastically rising global temperatures threaten the health and wellbeing of populations, solutions that drive policy action must be based on scientific evidence of which strategies work in different scenarios.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":58.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03276-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236097","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":"Data-driven risk stratification and precision management of pulmonary nodules detected on chest computed tomography","authors":"Chengdi Wang, Jun Shao, Yichu He, Jiaojiao Wu, Xingting Liu, Liuqing Yang, Ying Wei, Xiang Sean Zhou, Yiqiang Zhan, Feng Shi, Dinggang Shen, Weimin Li","doi":"10.1038/s41591-024-03211-3","DOIUrl":"https://doi.org/10.1038/s41591-024-03211-3","url":null,"abstract":"<p>The widespread implementation of low-dose computed tomography (LDCT) in lung cancer screening has led to the increasing detection of pulmonary nodules. However, precisely evaluating the malignancy risk of pulmonary nodules remains a formidable challenge. Here we propose a triage-driven Chinese Lung Nodules Reporting and Data System (C-Lung-RADS) utilizing a medical checkup cohort of 45,064 cases. The system was operated in a stepwise fashion, initially distinguishing low-, mid-, high- and extremely high-risk nodules based on their size and density. Subsequently, it progressively integrated imaging information, demographic characteristics and follow-up data to pinpoint suspicious malignant nodules and refine the risk scale. The multidimensional system achieved a state-of-the-art performance with an area under the curve (AUC) of 0.918 (95% confidence interval (CI) 0.918–0.919) on the internal testing dataset, outperforming the single-dimensional approach (AUC of 0.881, 95% CI 0.880–0.882). Moreover, C-Lung-RADS exhibited a superior sensitivity compared with Lung-RADS v2022 (87.1% versus 63.3%) in an independent cohort, which was screened using mobile computed tomography scanners to broaden screening accessibility in resource-constrained settings. With its foundation in precise risk stratification and tailored management, this system has minimized unnecessary invasive procedures for low-risk cases and recommended prompt intervention for extremely high-risk nodules to avert diagnostic delays. This approach has the potential to enhance the decision-making paradigm and facilitate a more efficient diagnosis of lung cancer during routine checkups as well as screening scenarios.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236145","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":"Exposure to extreme heat increases perinatal mortality in sub-Saharan Africa","authors":"","doi":"10.1038/s41591-024-03251-9","DOIUrl":"https://doi.org/10.1038/s41591-024-03251-9","url":null,"abstract":"Extreme heat events are expected to become more frequent because of climate change. Our analysis of almost 140,000 births across 16 hospitals in four countries in sub-Saharan Africa indicates 34% higher odds of perinatal mortality (stillbirth or death up to 24 hours after birth) if extreme heat occurred in the week preceding childbirth.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236146","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":"Author Correction: Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations.","authors":"Sebastian Moguilner, Sandra Baez, Hernan Hernandez, Joaquín Migeot, Agustina Legaz, Raul Gonzalez-Gomez, Francesca R Farina, Pavel Prado, Jhosmary Cuadros, Enzo Tagliazucchi, Florencia Altschuler, Marcelo Adrián Maito, María E Godoy, Josephine Cruzat, Pedro A Valdes-Sosa, Francisco Lopera, John Fredy Ochoa-Gómez, Alfredis Gonzalez Hernandez, Jasmin Bonilla-Santos, Rodrigo A Gonzalez-Montealegre, Renato Anghinah, Luís E d'Almeida Manfrinati, Sol Fittipaldi, Vicente Medel, Daniela Olivares, Görsev G Yener, Javier Escudero, Claudio Babiloni, Robert Whelan, Bahar Güntekin, Harun Yırıkoğulları, Hernando Santamaria-Garcia, Alberto Fernández Lucas, David Huepe, Gaetano Di Caterina, Marcio Soto-Añari, Agustina Birba, Agustin Sainz-Ballesteros, Carlos Coronel-Oliveros, Amanuel Yigezu, Eduar Herrera, Daniel Abasolo, Kerry Kilborn, Nicolás Rubido, Ruaridh A Clark, Ruben Herzog, Deniz Yerlikaya, Kun Hu, Mario A Parra, Pablo Reyes, Adolfo M García, Diana L Matallana, José Alberto Avila-Funes, Andrea Slachevsky, María I Behrens, Nilton Custodio, Juan F Cardona, Pablo Barttfeld, Ignacio L Brusco, Martín A Bruno, Ana L Sosa Ortiz, Stefanie D Pina-Escudero, Leonel T Takada, Elisa Resende, Katherine L Possin, Maira Okada de Oliveira, Alejandro Lopez-Valdes, Brian Lawlor, Ian H Robertson, Kenneth S Kosik, Claudia Duran-Aniotz, Victor Valcour, Jennifer S Yokoyama, Bruce Miller, Agustin Ibanez","doi":"10.1038/s41591-024-03294-y","DOIUrl":"https://doi.org/10.1038/s41591-024-03294-y","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":58.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291766","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":"Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors","authors":"Yoshiaki Nakamura, Hiroshi Ozaki, Makoto Ueno, Yoshito Komatsu, Satoshi Yuki, Taito Esaki, Hiroya Taniguchi, Yu Sunakawa, Kensei Yamaguchi, Ken Kato, Tadamichi Denda, Tomohiro Nishina, Naoki Takahashi, Taroh Satoh, Hisateru Yasui, Hironaga Satake, Eiji Oki, Takeshi Kato, Takashi Ohta, Nobuhisa Matsuhashi, Masahiro Goto, Naohiro Okano, Koushiro Ohtsubo, Kentaro Yamazaki, Riu Yamashita, Naoko Iida, Mihoko Yuasa, Hideaki Bando, Takayuki Yoshino","doi":"10.1038/s41591-024-03244-8","DOIUrl":"https://doi.org/10.1038/s41591-024-03244-8","url":null,"abstract":"<p>Although comprehensive genomic profiling has become standard in oncology for advanced solid tumors, the full potential of circulating tumor DNA (ctDNA)-based profiling in capturing tumor heterogeneity and guiding therapy selection remains underexploited, marked by a scarcity of evidence on its clinical impact and the assessment of intratumoral heterogeneity. The GOZILA study, a nationwide, prospective observational ctDNA profiling study, previously demonstrated higher clinical trial enrollment rates using liquid biopsy compared with tissue screening. This updated analysis of 4,037 patients further delineates the clinical utility of ctDNA profiling in advanced solid tumors, showcasing a significant enhancement in patient outcomes with a 24% match rate for targeted therapy. Patients treated with matched targeted therapy based on ctDNA profiling demonstrated significantly improved overall survival compared with those receiving unmatched therapy (hazard ratio, 0.54). Notably, biomarker clonality and adjusted plasma copy number were identified as predictors of therapeutic efficacy, reinforcing the value of ctDNA in reflecting tumor heterogeneity for precise treatment decisions. These new insights into the relationship between ctDNA characteristics and treatment outcomes advance our understanding beyond the initial enrollment benefits. Our findings advocate for the broader adoption of ctDNA-guided treatment, signifying an advancement in precision oncology and improving survival outcomes in advanced solid tumors.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234483","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":"ctDNA-based molecular residual disease and survival in resectable colorectal cancer","authors":"Yoshiaki Nakamura, Jun Watanabe, Naoya Akazawa, Keiji Hirata, Kozo Kataoka, Mitsuru Yokota, Kentaro Kato, Masahito Kotaka, Yoshinori Kagawa, Kun-Huei Yeh, Saori Mishima, Hiroki Yukami, Koji Ando, Masaaki Miyo, Toshihiro Misumi, Kentaro Yamazaki, Hiromichi Ebi, Kenji Okita, Atsushi Hamabe, Hiroki Sokuoka, Satoshi Kobayashi, George Laliotis, Vasily N. Aushev, Shruti Sharma, Adham Jurdi, Minetta C. Liu, Alexey Aleshin, Matthew Rabinowitz, Hideaki Bando, Hiroya Taniguchi, Ichiro Takemasa, Takeshi Kato, Daisuke Kotani, Masaki Mori, Takayuki Yoshino, Eiji Oki","doi":"10.1038/s41591-024-03254-6","DOIUrl":"https://doi.org/10.1038/s41591-024-03254-6","url":null,"abstract":"<p>The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II–III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, <i>P</i> &lt; 0.0001) and overall survival (OS; HR: 9.68, <i>P</i> &lt; 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, <i>P</i> &lt; 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234481","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":"Author Correction: Not all AI health tools with regulatory authorization are clinically validated.","authors":"Sammy Chouffani El Fassi, Adonis Abdullah, Ying Fang, Sarabesh Natarajan, Awab Bin Masroor, Naya Kayali, Simran Prakash, Gail E Henderson","doi":"10.1038/s41591-024-03293-z","DOIUrl":"https://doi.org/10.1038/s41591-024-03293-z","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":58.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291767","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 nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial","authors":"Iris Nederlof, Olga I. Isaeva, Manon de Graaf, Robbert C. A. M. Gielen, Noor A. M. Bakker, Adrianne L. Rolfes, Hannah Garner, Bram Boeckx, Joleen J. H. Traets, Ingrid A. M. Mandjes, Michiel de Maaker, Thomas van Brussel, Maksim Chelushkin, Elisa Champanhet, Marta Lopez-Yurda, Koen van de Vijver, José G. van den Berg, Ingrid Hofland, Natasja Klioueva, Ritse M. Mann, Claudette E. Loo, Frederieke H. van Duijnhoven, Victoria Skinner, Sylvia Luykx, Emile Kerver, Ekaterina Kalashnikova, Marloes G. J. van Dongen, Gabe S. Sonke, Sabine C. Linn, Christian U. Blank, Karin E. de Visser, Roberto Salgado, Lodewyk F. A. Wessels, Caroline A. Drukker, Ton N. Schumacher, Hugo M. Horlings, Diether Lambrechts, Marleen Kok","doi":"10.1038/s41591-024-03249-3","DOIUrl":"https://doi.org/10.1038/s41591-024-03249-3","url":null,"abstract":"<p>Immune checkpoint inhibition (ICI) with chemotherapy is now the standard of care for stage II–III triple-negative breast cancer; however, it is largely unknown for which patients ICI without chemotherapy could be an option and what the benefit of combination ICI could be. The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary end point, twofold increase in CD8⁺ T cells or <i>IFNG</i>), providing a rationale for neoadjuvant ICI without chemotherapy. Here, in window-of-opportunity cohorts A (4 weeks of anti-PD-1) and B (4 weeks of anti-PD-1 + anti-CTLA4), we observed immune activation in 53% (8 of 15) and 60% (9 of 15) of patients, respectively. High levels of tumor-infiltrating lymphocytes correlated with response. Single-cell RNA sequencing revealed that higher pretreatment tumor-reactive CD8⁺ T cells, follicular helper T cells and shorter distances between tumor and CD8⁺ T cells correlated with response. Higher levels of regulatory T cells after treatment were associated with nonresponse. Based on these data, we opened cohort C for patients with high levels of tumor-infiltrating lymphocytes (≥50%) who received 6 weeks of neoadjuvant anti-PD-1 + anti-CTLA4 followed by surgery (primary end point, pathological complete response). Overall, 53% (8 of 15) of patients had a major pathological response (&lt;10% viable tumor) at resection, with 33% (5 of 15) having a pathological complete response. All cohorts met Simon’s two-stage threshold for expansion to stage II. We observed grade ≥3 adverse events for 17% of patients and a high rate (57%) of immune-mediated endocrinopathies. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early triple-negative breast cancer. ClinicalTrials.gov registration: NCT03815890.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234487","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 nivolumab and relatlimab in locally advanced MMR-deficient colon cancer: a phase 2 trial","authors":"Peter G. M. de Gooyer, Yara L. Verschoor, Lauren D. W. van den Dungen, Sara Balduzzi, Hendrik A. Marsman, Marnix H. Geukes Foppen, Cecile Grootscholten, Simone Dokter, Anne G. den Hartog, Wieke H. M. Verbeek, Karlijn Woensdregt, Joris J. van den Broek, Steven J. Oosterling, Ton N. Schumacher, Koert F. D. Kuhlmann, Regina G. H. Beets-Tan, John B. A. G. Haanen, Monique E. van Leerdam, Jose G. van den Berg, Myriam Chalabi","doi":"10.1038/s41591-024-03250-w","DOIUrl":"https://doi.org/10.1038/s41591-024-03250-w","url":null,"abstract":"<p>Mismatch repair deficiency (dMMR) is found in approximately 15% of non-metastatic colon cancers (CCs) and is characterized by a defective DNA mismatch repair system, resulting in hypermutated and highly immunogenic tumors. Although patients with dMMR CC have limited benefit from chemotherapy, these tumors have been shown to respond exceptionally well to neoadjuvant anti-PD-1 plus anti-CTLA-4, with high rates of pathologic responses. Here, based on data from melanoma studies, we postulated a high efficacy and favorable toxicity profile of anti-PD-1 plus anti-LAG-3. In the NICHE-3 study, a total of 59 patients with locally advanced dMMR CC were treated with two 4-weekly cycles of nivolumab (480 mg) plus relatlimab (480 mg) before surgery. Pathologic response was observed in 57 of 59 (97%; 95% confidence interval (CI): 88–100%) patients, meeting the primary endpoint. Responses included 54 (92%; 95% CI: 81–97%) major pathologic responses (≤10% residual viable tumor) and 40 (68%; 95% CI: 54–79%) pathologic complete responses. With a median follow-up of 8 months (range, 2–19), one patient had recurrence of disease. The treatment displayed an acceptable safety profile, with all-grade and grade 3–4 immune-related adverse events (irAEs) occurring in 80% and 10% of patients, respectively. The most common irAEs were infusion-related reactions (29%), thyroid dysfunction (22%) and fatigue (20%). In conclusion, our results show that neoadjuvant nivolumab/relatlimab induces high rates of pathologic responses and that further investigation of this treatment in larger studies is warranted. These data add to the body of evidence in support of neoadjuvant immunotherapy regimens in dMMR CC. ClinicalTrials.gov identifier: NCT03026140.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233351","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":"Datopotamab–deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial","authors":"Rebecca A. Shatsky, Meghna S. Trivedi, Christina Yau, Rita Nanda, Hope S. Rugo, Marie Davidian, Butch Tsiatis, Anne M. Wallace, A. Jo Chien, Erica Stringer-Reasor, Judy C. Boughey, Coral Omene, Mariya Rozenblit, Kevin Kalinsky, Anthony D. Elias, Christos Vaklavas, Heather Beckwith, Nicole Williams, Mili Arora, Chaitali Nangia, Evanthia T. Roussos Torres, Brittani Thomas, Kathy S. Albain, Amy S. Clark, Carla Falkson, Dawn L. Hershman, Claudine Isaacs, Alexandra Thomas, Jennifer Tseng, Amy Sanford, Kay Yeung, Sarah Boles, Yunni Yi Chen, Laura Huppert, Nusrat Jahan, Catherine Parker, Karthik Giridhar, Frederick M. Howard, M. Michele Blackwood, Tara Sanft, Wen Li, Natsuko Onishi, Adam L. Asare, Philip Beineke, Peter Norwood, Lamorna Brown-Swigart, Gillian L. Hirst, Jeffrey B. Matthews, Brian Moore, W. Fraser Symmans, Elissa Price, Diane Heditsian, Barbara LeStage, Jane Perlmutter, Paula Pohlmann, Angela DeMichele, Douglas Yee, Laura J. van ’t Veer, Nola M. Hylton, Laura J. Esserman","doi":"10.1038/s41591-024-03267-1","DOIUrl":"https://doi.org/10.1038/s41591-024-03267-1","url":null,"abstract":"<p>Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody–drug conjugate, datopotamab–deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin–cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin–cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.</p><p>ClinicalTrials.gov registration: NCT01042379.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231740","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}