New England Journal of Medicine最新文献

{"title":"Debating Race and the Diagnosis of Anemia - How Medicine Moved Away from Race-Based Standards.","authors":"Wingel Xue, David S Jones","doi":"10.1056/NEJMms2413444","DOIUrl":"https://doi.org/10.1056/NEJMms2413444","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 21","pages":"2168-2173"},"PeriodicalIF":96.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227668","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":"Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. Reply.","authors":"Jennifer R Brown, Kara Miller, Veerendra Munugalavadla","doi":"10.1056/NEJMc2503839","DOIUrl":"https://doi.org/10.1056/NEJMc2503839","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"392 21","pages":"2181"},"PeriodicalIF":96.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227670","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":"<i>Corynebacterium diphtheriae</i> Outbreak in Migrant Populations in Europe.","authors":"Andreas Hoefer, Helena Seth-Smith, Federica Palma, Stefanie Schindler, Luca Freschi, Alexandra Dangel, Anja Berger, Joshua D'Aeth, Rebecca Cordery, Enrique Delgado-Rodriguez, Eva Gruner, Domenica Flury, Vladimira Hinic, Julian Kofler, Reto Lienhard, Rob Mariman, Oliver Nolte, Adrian Schibli, Julie Toubiana, Marianna Traugott, Stephanie Jacquinet, Alexander Indra, Norman K Fry, Daniel Palm, Andreas Sing, Sylvain Brisse, Adrian Egli","doi":"10.1056/NEJMoa2311981","DOIUrl":"https://doi.org/10.1056/NEJMoa2311981","url":null,"abstract":"<p><strong>Background: </strong>A surge of cases of <i>Corynebacterium diphtheriae</i> infection was observed in reception centers for migrants in Europe beginning in the summer of 2022. Most of the cases were cutaneous, although some respiratory cases as well as one death were reported. A pan-European consortium was created to assess the clinical, epidemiologic, and microbiologic features of this outbreak.</p><p><strong>Methods: </strong>We assessed cases of toxigenic <i>C. diphtheriae</i> infection that were reported in 10 European countries from January through November 2022. Data regarding countries of origin and transit routes were obtained from interviews with the patients. Whole-genome sequencing and antimicrobial-susceptibility testing were performed on bacterial isolates that were obtained from the patients. The phylogenetic relationships of the isolates and their antimicrobial-resistance genes were evaluated.</p><p><strong>Results: </strong>A total of 363 toxigenic <i>C. diphtheriae</i> isolates were identified among 362 patients during the study period. Clinical data were available for 346 patients (95.6%): 268 (77.5%) had cutaneous diphtheria, 53 (15.3%) had respiratory diphtheria (11 [3.2%] had a pseudomembrane), and 9 (2.6%) had both respiratory and cutaneous symptoms. Four major genetic clusters were identified, which indicated the multiclonal nature of the outbreak. The <i>ermX</i> gene (which codes for erythromycin resistance) and the <i>pbp2m</i> and <i>blaOXA-2</i> genes (which code for beta-lactam resistance) were detected in a subgroup of isolates. Isolates that carried <i>ermX</i> were resistant to erythromycin, and isolates that carried <i>pbp2m</i> were resistant to penicillin but were susceptible to amoxicillin. On the basis of the genomic variation within the four genetic clusters, their most recent common ancestors were estimated to have existed between 2017 and 2020.</p><p><strong>Conclusions: </strong>The distribution of each genetic cluster of <i>C. diphtheriae</i> isolates across multiple countries in Europe showed repeated cross-border spread. The large number of <i>C. diphtheriae</i> infections among migrants is a cause for concern, particularly given that antimicrobial-resistance phenotypes threaten the efficacy of first-line treatments. (Funded by the Bavarian State Ministry of Health, Care, and Prevention and others.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227662","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":"Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma.","authors":"Aurore Perrot, Jérôme Lambert, Cyrille Hulin, Andrea Pieragostini, Lionel Karlin, Bertrand Arnulf, Philippe Rey, Laurent Garderet, Margaret Macro, Martine Escoffre-Barbe, Julie Gay, Thomas Chalopin, Romain Gounot, Jean-Marc Schiano, Mohamad Mohty, Xavier Leleu, Salomon Manier, Clara Mariette, Carine Chaleteix, Thorsten Braun, Bernard De Prijck, Hervé Avet-Loiseau, Jean-Yves Mary, Jill Corre, Philippe Moreau, Cyrille Touzeau","doi":"10.1056/NEJMoa2505133","DOIUrl":"https://doi.org/10.1056/NEJMoa2505133","url":null,"abstract":"<p><strong>Background: </strong>Measurable residual disease (MRD) is a major prognostic factor in newly diagnosed multiple myeloma. An assessment of an MRD-guided consolidation strategy in patients who are eligible for autologous stem-cell transplantation (ASCT) may be useful.</p><p><strong>Methods: </strong>In this phase 3 trial, we randomly assigned transplantation-eligible patients with newly diagnosed myeloma who had completed induction therapy with isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) to receive consolidation therapy according to their MRD status. Patients who were MRD-negative at 10^-5 sensitivity (i.e., <1 cancer cell per 100,000 normal cells, as assessed by next-generation sequencing were assigned to undergo ASCT and receive Isa-KRd for two cycles (ASCT group) or to receive Isa-KRd for six cycles (Isa-KRd group). Patients who were MRD-positive at 10^-5 sensitivity were assigned to undergo tandem ASCT (two ASCTs within a short period; tandem ASCT group) or to undergo ASCT and receive Isa-KRd for two cycles (single ASCT group). The primary end point was an MRD-negative status at 10^-6 sensitivity before maintenance therapy.</p><p><strong>Results: </strong>Among 485 patients who were MRD-negative at 10^-5 sensitivity after induction, a premaintenance MRD-negative status at 10^-6 sensitivity occurred in 86% in the ASCT group and in 84% in the Isa-KRd group (adjusted relative risk, 1.02; 95% confidence interval [CI], 0.95 to 1.10; P = 0.64). Among 233 patients who were MRD-positive at 10^-5 sensitivity after induction, a premaintenance MRD-negative status at 10^-6 sensitivity occurred in 32% in the tandem ASCT group and in 40% in the single ASCT group (adjusted relative risk, 0.82; 95% CI, 0.58 to 1.15; P = 0.31); 15% of the patients in the tandem ASCT group did not undergo a second ASCT. During consolidation, disease progression occurred in 5 patients and death unrelated to disease progression occurred in 2 patients - all were in the Isa-KRd or tandem ASCT groups. No new safety signals were observed. The median follow-up was 16.8 months in the ASCT and Isa-KRd groups and 16.3 months in the tandem ASCT and single ASCT groups.</p><p><strong>Conclusions: </strong>Among patients who were MRD-negative at 10^-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10^-6 sensitivity was not significantly higher with ASCT than with Isa-KRd. Among patients who were MRD-positive status at 10^-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10^-6 sensitivity was not significantly higher with tandem ASCT than with single ASCT. (Funded by Intergroupe Francophone du Myélome and others; MIDAS ClinicalTrials.gov number, NCT04934475.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210261","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":"Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer.","authors":"Fatima Cardoso, Susanne Parke, Donal J Brennan, Paula Briggs, Gilbert Donders, Nick Panay, Nazanin Haseli-Mashhadi, Michael Block, Cecilia Caetano, Maja Francuski, Claudia Haberland, Kaisa Laapas, Christian Seitz, Lineke Zuurman","doi":"10.1056/NEJMoa2415566","DOIUrl":"https://doi.org/10.1056/NEJMoa2415566","url":null,"abstract":"<p><strong>Background: </strong>Women receiving endocrine therapy for hormone receptor (HR)-positive breast cancer or its prevention among those at high risk for breast cancer commonly have vasomotor symptoms. Data are lacking on the effects of elinzanetant, a neurokinin-targeted therapy shown to be effective in treating vasomotor symptoms, in this population.</p><p><strong>Methods: </strong>We performed a phase 3 trial involving women 18 to 70 years of age with moderate-to-severe vasomotor symptoms associated with endocrine therapy for HR-positive breast cancer or its prevention. Women were randomly assigned in a 2:1 ratio to receive once-daily elinzanetant at a dose of 120 mg for 52 weeks or once-daily placebo for 12 weeks followed by once-daily elinzanetant at a dose of 120 mg for 40 weeks. The primary end points were the change in the mean daily frequency of moderate-to-severe vasomotor symptoms from baseline to week 4 and to week 12.</p><p><strong>Results: </strong>A total of 316 participants were assigned to the elinzanetant group and 158 to the placebo-elinzanetant group. At baseline, the mean daily frequency of moderate-to-severe vasomotor symptoms was 11.4 episodes (95% confidence interval [CI], 10.7 to 12.2) in the elinzanetant group and 11.5 episodes (95% CI, 10.5 to 12.5) in the placebo-elinzanetant group. At week 4, the mean change from baseline in the mean daily frequency of moderate-to-severe vasomotor symptoms was -6.5 episodes (95% CI, -7.2 to -5.8) among those who were receiving elinzanetant and -3.0 episodes (95% CI, -3.9 to -2.2) among those who were receiving placebo (least-squares mean difference, -3.5 episodes; 95% CI, -4.4 to -2.6; P<0.001). At week 12, the mean change was -7.8 episodes (95% CI, -8.5 to -7.1) among those receiving elinzanetant and -4.2 episodes (95% CI, -5.2 to -3.2) among those receiving placebo (least-squares mean difference, -3.4 episodes; 95% CI, -4.2 to -2.5; P<0.001). During weeks 1 through 12, a total of 220 participants (69.8%) receiving elinzanetant and 98 (62.0%) receiving placebo reported at least one adverse event that occurred while receiving elinzanetant or placebo, with the most common being headache, fatigue, and somnolence. Serious adverse events occurred during weeks 1 through 12 in 8 participants (2.5%) receiving elinzanetant and 1 participant (0.6%) receiving placebo.</p><p><strong>Conclusions: </strong>Elinzanetant led to a significantly lower frequency of vasomotor symptoms associated with endocrine therapy than placebo. (Funded by Bayer; OASIS-4 ClinicalTrials.gov number, NCT05587296.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200784","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":"Menopausal Symptom Management in Breast Cancer Survivors - A Promising New Option.","authors":"Ann H Partridge","doi":"10.1056/NEJMe2506475","DOIUrl":"https://doi.org/10.1056/NEJMe2506475","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200786","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":"Overall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer.","authors":"Patrick M Forde, Jonathan D Spicer, Mariano Provencio, Tetsuya Mitsudomi, Mark M Awad, Changli Wang, Shun Lu, Enriqueta Felip, Scott J Swanson, Julie R Brahmer, Keith Kerr, Janis M Taube, Tudor-Eliade Ciuleanu, Fumihiro Tanaka, Gene B Saylors, Ke-Neng Chen, Hiroyuki Ito, Moishe Liberman, Claudio Martin, Stephen Broderick, Lily Wang, Junliang Cai, Quyen Duong, Stephanie Meadows-Shropshire, Joseph Fiore, Sumeena Bhatia, Nicolas Girard","doi":"10.1056/NEJMoa2502931","DOIUrl":"https://doi.org/10.1056/NEJMoa2502931","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant nivolumab plus chemotherapy significantly improved pathological complete response and event-free survival in patients with resectable non-small-cell lung cancer (NSCLC) in a phase 3 trial. Data are needed on overall survival.</p><p><strong>Methods: </strong>In this open-label, phase 3 trial, patients with stage IB to IIIA resectable NSCLC were randomly assigned to receive nivolumab plus chemotherapy or chemotherapy alone for three cycles, followed by surgery. The primary end points were event-free survival and pathological complete response. Here, we report the results of the planned analysis of overall survival.</p><p><strong>Results: </strong>A total of 358 patients were concurrently assigned to receive nivolumab plus chemotherapy (179 patients) or chemotherapy alone (179 patients). The final analysis of overall survival significantly favored neoadjuvant nivolumab plus chemotherapy over chemotherapy (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.52 to 0.10; P = 0.048). At a median follow-up of 68.4 months, the 5-year overall survival was 65.4% with nivolumab plus chemotherapy and 55.0% with chemotherapy alone, with consistency across most subgroups. In exploratory analyses, the 5-year overall survival in the nivolumab-plus-chemotherapy group was 95.3% (95% CI, 82.7 to 98.8) among the patients with a pathological complete response and 55.7% (95% CI, 46.9 to 63.7) among those without such a response; survival was 75.0% among the patients with presurgery clearance of circulating tumor DNA (ctDNA) and 52.6% among those without such clearance. No new safety signals were observed.</p><p><strong>Conclusions: </strong>Three cycles of neoadjuvant nivolumab plus chemotherapy significantly improved overall survival among patients with resectable NSCLC as compared with chemotherapy alone. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200788","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":"Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy.","authors":"Giannis Mountzios, Longhua Sun, Byoung Chul Cho, Umut Demirci, Sofia Baka, Mahmut Gümüş, Antonio Lugini, Bo Zhu, Yan Yu, Ippokratis Korantzis, Ji-Youn Han, Tudor-Eliade Ciuleanu, Myung-Ju Ahn, Pedro Rocha, Julien Mazières, Sally C M Lau, Martin Schuler, Fiona Blackhall, Tatsuya Yoshida, Taofeek K Owonikoko, Luis Paz-Ares, Tony Jiang, Ali Hamidi, Diana Gauto, Gonzalo Recondo, Charles M Rudin","doi":"10.1056/NEJMoa2502099","DOIUrl":"https://doi.org/10.1056/NEJMoa2502099","url":null,"abstract":"<p><strong>Background: </strong>Tarlatamab, a bispecific delta-like ligand 3-directed T-cell engager immunotherapy, received accelerated approval for the treatment of patients with previously treated small-cell lung cancer. Whether tarlatamab is more effective than chemotherapy in the treatment of patients whose small-cell lung cancer has progressed during or after initial platinum-based chemotherapy is not known.</p><p><strong>Methods: </strong>We conducted a multinational, phase 3, open-label trial to compare tarlatamab with chemotherapy as second-line treatment in patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. Patients were randomly assigned to receive tarlatamab or chemotherapy (topotecan, lurbinectedin, or amrubicin). The primary end point was overall survival. Key secondary end points were investigator-assessed progression-free survival and patient-reported outcomes. Results of the prespecified interim analysis (data-cutoff date, January 29, 2025) are reported.</p><p><strong>Results: </strong>A total of 509 patients were randomly assigned to receive tarlatamab (254 patients) or chemotherapy (255 patients). Treatment with tarlatamab resulted in significantly longer overall survival than chemotherapy (median, 13.6 months [95% confidence interval {CI}, 11.1 to not reached] vs. 8.3 months [95% CI, 7.0 to 10.2]; stratified hazard ratio for death, 0.60; 95% CI, 0.47 to 0.77; P<0.001). Tarlatamab treatment also had a significant benefit with respect to progression-free survival and cancer-related dyspnea and cough as compared with chemotherapy. The incidence of adverse events of grade 3 or higher was lower with tarlatamab than with chemotherapy (54% vs. 80%), as was the incidence of adverse events resulting in treatment discontinuation (5% vs. 12%).</p><p><strong>Conclusions: </strong>Treatment with tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. (Funded by Amgen; DeLLphi-304 ClinicalTrials.gov number, NCT05740566.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200791","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":"Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer.","authors":"Yelena Y Janjigian, Salah-Eddin Al-Batran, Zev A Wainberg, Kei Muro, Daniela Molena, Eric Van Cutsem, Woo Jin Hyung, Lucjan Wyrwicz, Do-Youn Oh, Takeshi Omori, Markus Moehler, Marcelo Garrido, Sulene C S Oliveira, Moishe Liberman, Victor Castro Oliden, Elizabeth C Smyth, Alexander Stein, Mehmet Bilici, Maria Lorena Alvarenga, Vadim Kozlov, Fernando Rivera, Akihito Kawazoe, Olivier Serrano, Eric Heilbron, Alejandra Negro, John F Kurland, Josep Tabernero","doi":"10.1056/NEJMoa2503701","DOIUrl":"https://doi.org/10.1056/NEJMoa2503701","url":null,"abstract":"<p><strong>Background: </strong>Perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) is a standard therapy for resectable gastric and gastroesophageal junction adenocarcinomas, but recurrence rates remain high. Immunotherapy plus chemotherapy may improve outcomes.</p><p><strong>Methods: </strong>In a phase 3, multinational, double-blind, randomized trial, we assigned participants with resectable gastric or gastroesophageal junction adenocarcinoma, in a 1:1 ratio, to receive durvalumab at a dose of 1500 mg or placebo every 4 weeks plus FLOT for 4 cycles (2 cycles each of neoadjuvant and adjuvant therapy), followed by durvalumab or placebo every 4 weeks for 10 cycles. The primary end point was event-free survival; secondary end points included overall survival and pathological complete response.</p><p><strong>Results: </strong>A total of 474 participants were randomly assigned to the durvalumab group, and 474 to the placebo group (median follow-up, 31.5 months; interquartile range, 26.7 to 36.6). Two-year event-free survival (Kaplan-Meier estimate) was 67.4% among the participants in the durvalumab group and 58.5% among those in the placebo group (hazard ratio for event or death, 0.71; 95% confidence interval [CI], 0.58 to 0.86; P<0.001). Two-year overall survival was 75.7% in the durvalumab group and 70.4% in the placebo group (piecewise hazard ratio for death during months 0 to 12, 0.99 [95% CI, 0.70 to 1.39], and during the period from month 12 onward, 0.67 [95% CI, 0.50 to 0.90]; P = 0.03 by a stratified log-rank test [exceeding the significance threshold of P<0.0001]). The percentage of participants with a pathological complete response was 19.2% in the durvalumab group and 7.2% in the placebo group (relative risk, 2.69 [95% CI, 1.86 to 3.90]). Adverse events with a maximum grade of 3 or 4 were reported in 340 participants (71.6%) in the durvalumab group and in 334 (71.2%) in the placebo group. The percentage of participants with delayed surgery was 10.1% and 10.8%, respectively, and the percentage with delayed initiation of adjuvant treatment was 2.3% and 4.6%.</p><p><strong>Conclusions: </strong>Perioperative durvalumab plus FLOT led to significantly better event-free survival outcomes than FLOT alone among participants with resectable gastric or gastroesophageal junction adenocarcinoma. (Funded by AstraZeneca; MATTERHORN ClinicalTrials.gov number, NCT04592913.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200789","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":"First-Line Camizestrant for Emerging <i>ESR1</i>-Mutated Advanced Breast Cancer.","authors":"François-Clément Bidard, Erica L Mayer, Yeon Hee Park, Wolfgang Janni, Cynthia Ma, Massimo Cristofanilli, Giampaolo Bianchini, Kevin Kalinsky, Hiroji Iwata, Stephen Chia, Peter A Fasching, Adam Brufsky, Zbigniew Nowecki, Javier Pascual, Lionel Moreau, Shin-Cheh Chen, Nuri Karadurmus, Einav Nili Gal-Yam, Kyung Hae Jung, Sonia Pernas, Sasha McClain, Wei He, Teresa Klinowska, Cynthia Huang-Bartlett, Nicholas C Turner","doi":"10.1056/NEJMoa2502929","DOIUrl":"https://doi.org/10.1056/NEJMoa2502929","url":null,"abstract":"<p><strong>Background: </strong>Mutations in <i>ESR1</i> are the most common mechanism of acquired resistance to treatment with an aromatase inhibitor plus a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor for advanced breast cancer. Camizestrant, a next-generation selective estrogen-receptor (ER) degrader and complete ER antagonist, has shown antitumor activity in ER-positive advanced breast cancer.</p><p><strong>Methods: </strong>We tested patients with advanced breast cancer with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors for <i>ESR1</i> mutations in circulating tumor DNA (ctDNA) once every 2 to 3 months. All the patients had received at least 6 months of first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib). Patients who were found to have an <i>ESR1</i> mutation and did not have radiologic progression were assigned in a 1:1 ratio to switch to camizestrant (75 mg once daily) with a continued CDK4/6 inhibitor plus placebo in place of an aromatase inhibitor or to continue to receive an aromatase inhibitor plus a CDK4/6 inhibitor plus placebo in place of camizestrant. The primary outcome was investigator-assessed progression-free survival.</p><p><strong>Results: </strong>A total of 3256 patients were tested for an <i>ESR1</i> mutation. The 315 eligible patients were assigned to switch to camizestrant (157 patients) or to continue to receive an aromatase inhibitor (158 patients). At an interim analysis at a median follow-up of 12.6 months, the median progression-free survival was 16.0 months (95% confidence interval [CI], 12.7 to 18.2) in the camizestrant group and 9.2 months (95% CI, 7.2 to 9.5) in the aromatase-inhibitor group (hazard ratio for progression or death, 0.44; 95% CI, 0.31 to 0.60; P<0.0001). The median time until a deterioration in the patient-reported global health status and quality of life occurred was 23.0 months with camizestrant and 6.4 months with an aromatase inhibitor (hazard ratio, 0.53; 95% CI, 0.33 to 0.82). The frequency of discontinuation because of adverse events was 1.3% with camizestrant and 1.9% with an aromatase inhibitor.</p><p><strong>Conclusions: </strong>In patients with ER-positive, HER2-negative advanced breast cancer with an <i>ESR1</i> mutation that emerged during treatment, those who were switched to camizestrant with continuation of a CDK4/6 inhibitor during first-line therapy had significantly longer progression-free survival than those who maintained the aromatase-inhibitor combination. (Funded by AstraZeneca; SERENA-6 ClinicalTrials.gov number, NCT04964934.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":""},"PeriodicalIF":96.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200785","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}