Journal of Clinical Oncology最新文献

{"title":"Air Pollution and Breast Cancer Incidence in the Multiethnic Cohort Study.","authors":"Anna H Wu, Jun Wu, Chiuchen Tseng, Daniel O Stram, Salma Shariff-Marco, Timothy Larson, Deborah Goldberg, Scott Fruin, Anqi Jiao, Pushkar P Inamdar, Ugonna Ihenacho, Loïc Le Marchand, Lynne Wilkens, Christopher Haiman, Beate Ritz, Iona Cheng","doi":"10.1200/JCO.24.00418","DOIUrl":"10.1200/JCO.24.00418","url":null,"abstract":"<p><strong>Purpose: </strong>Recent studies suggested fine particulate matter (PM_2.5) exposure increases the risk of breast cancer, but evidence among racially and ethnically diverse populations remains sparse.</p><p><strong>Materials and methods: </strong>Among 58,358 California female participants of the Multiethnic Cohort (MEC) Study followed for an average of 19.3 years (1993-2018), we used Cox proportional hazards regression to examine associations of time-varying PM with invasive breast cancer risk (n = 3,524 cases; 70% African American and Latino females), adjusting for sociodemographics and lifestyle factors. Subgroup analyses were conducted for race and ethnicity, hormone receptor status, and breast cancer risk factors.</p><p><strong>Results: </strong>Satellite-based PM_2.5 was associated with a statistically significant increased incidence of breast cancer (hazard ratio [HR] per 10 μg/m³, 1.28 [95% CI, 1.08 to 1.51]). We found no evidence of heterogeneity in associations by race and ethnicity and hormone receptor status. Family history of breast cancer showed evidence of heterogeneity in PM_2.5-associations (<i>P</i>_{heterogeneity} = .046). In a meta-analysis of the MEC and 10 other prospective cohorts, breast cancer incidence increased in association with exposure to PM_2.5 (HR per 10 μg/m³ increase, 1.05 [95% CI, 1.00 to 1.10]; <i>P</i> = .064).</p><p><strong>Conclusion: </strong>Findings from this large multiethnic cohort with long-term air pollutant exposure and published prospective cohort studies support PM_2.5 as a risk factor for breast cancer. As about half of breast cancer cannot be explained by established breast cancer risk factors and incidence is continuing to increase, particularly in low- and middle-income countries, our results highlight that breast cancer prevention should include not only individual-level behavior-centered approaches but also population-wide policies and regulations to curb PM_2.5 exposure.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"273-284"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390894","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":"Reply to P. de Boissieu et al.","authors":"David R Spigel, Afshin Dowlati, Yuanbin Chen, Alejandro Navarro, James Chih-Hsin Yang, Goran Stojanovic, Maria Jove, Patricia Rich, Zoran G Andric, Yi-Long Wu, Charles M Rudin, Huanyu Chen, Li Zhang, Stanley Yeung, Fawzi Benzaghou, Luis Paz-Ares, Paul A Bunn","doi":"10.1200/JCO-24-01374","DOIUrl":"10.1200/JCO-24-01374","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"355-356"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390913","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 Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01.","authors":"Aditya Bardia, Komal Jhaveri, Seock-Ah Im, Sonia Pernas, Michelino De Laurentiis, Shusen Wang, Noelia Martínez Jañez, Giuliano Borges, David W Cescon, Masaya Hattori, Yen-Shen Lu, Erika Hamilton, Qingyuan Zhang, Junji Tsurutani, Kevin Kalinsky, Pedro Emanuel Rubini Liedke, Lu Xu, Rick M Fairhurst, Sabrina Khan, Neelima Denduluri, Hope S Rugo, Binghe Xu, Barbara Pistilli","doi":"10.1200/JCO.24.00920","DOIUrl":"10.1200/JCO.24.00920","url":null,"abstract":"<p><strong>Purpose: </strong>The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer.</p><p><strong>Methods: </strong>Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS).</p><p><strong>Results: </strong>Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367). Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; <i>P</i> < .0001). Consistent PFS benefit was observed across subgroups. Although OS data were not mature, a trend favoring Dato-DXd was observed (HR, 0.84 [95% CI, 0.62 to 1.14]). The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% <i>v</i> 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC.</p><p><strong>Conclusion: </strong>Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile, compared with ICC. Results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2‒ breast cancer who have received one to two previous lines of chemotherapy in this setting.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"285-296"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288211","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":"The Retrofit: Lessons From Sotorasib's Dosing Conundrum.","authors":"Harpreet Singh, Paz J Vellanki, Richard Pazdur","doi":"10.1200/JCO.24.00310","DOIUrl":"10.1200/JCO.24.00310","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"248-250"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390914","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":"Growing Evidence for the Role of Air Pollution in Breast Cancer Development.","authors":"Alexandra J White","doi":"10.1200/JCO-24-01987","DOIUrl":"10.1200/JCO-24-01987","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"244-247"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522037","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":"Phase Ib Study for the Combination of Doxorubicin, Dacarbazine, and Nivolumab as the Upfront Treatment in Patients With Advanced Leiomyosarcoma: A Study by the Spanish Sarcoma Group (GEIS).","authors":"Javier Martin-Broto, Roberto Diaz-Beveridge, David Moura, Rafael Ramos, Javier Martinez-Trufero, Irene Carrasco, Ana Sebio, Enrique González-Billalabeitia, Antonio Gutierrez, Javier Fernandez-Jara, Laura Hernández-Vargas, Josefina Cruz, Claudia Valverde, Nadia Hindi","doi":"10.1200/JCO.24.00358","DOIUrl":"10.1200/JCO.24.00358","url":null,"abstract":"<p><strong>Purpose: </strong>Doxorubicin, alongside a select group of cytotoxic agents, is capable of inducing an adaptive immune response via a well-established peculiar type of tumor cell death called immunogenic cell death (ICD). We hypothesize that combining doxorubicin and dacarbazine with nivolumab may enhance therapeutic efficacy by exerting synergy in the ICD circuit. We hereby present a phase Ib trial with this combination.</p><p><strong>Patients and methods: </strong>Patients with advanced leiomyosarcoma and anthracycline-naïve were eligible. The initial dose level consisted of doxorubicin 75 mg/m² once on day 1, once every three weeks, followed by dacarbazine 400 mg/m² once on days 1 and 2, once every three weeks, plus nivolumab 360 mg once on day 2, once every 3 weeks, for six courses and then 1 year of nivolumab. A (-1) dose level was the same regimen but with nivolumab 240 mg. A classic 3 + 3 phase-I design was used to determine the recommended phase-II dose (RP2D). Secondary end points included overall response rate, safety profile, survival, and translational research.</p><p><strong>Results: </strong>From January 2002 to July 2023, 24 patients were enrolled and 23 were evaluable for efficacy, excluding one patient because of noncompliant dose. All patients were treated with the initial dose level, then the RP2D. Toxicity was mild, with the most frequent being grade 4 toxicity neutropenia (16.7%) and thrombocytopenia (8.3%), while no grade 5 toxicity occurred. The centrally reviewed objective response rate was as follows: partial response 56.5%, stable disease 39.1%, and progression 4.4%. The 6-month progression-free survival (PFS) rate was 80% (95% CI, 63 to 98). Dynamic increases of HMGB1 in blood significantly correlated with longer PFS.</p><p><strong>Conclusion: </strong>This scheme of doxorubicin, dacarbazine, and nivolumab is feasible and well tolerated. Clinical activity is encouraging and the prognostic impact of HMGB1 supports the relevance of ICD activation. Further clinical research is already underway with this concept in leiomyosarcoma.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"297-307"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365402","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>UGT1A1</i> Testing for the Risk of Nanoliposomal Irinotecan-Related Toxicity.","authors":"Yao Liang, Yuichi Ando","doi":"10.1200/JCO-24-01366","DOIUrl":"10.1200/JCO-24-01366","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"357"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522036","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":"Targeting DKK1 to Remodel the Tumor Microenvironment and Enhance Immune Checkpoint Blockade Therapy.","authors":"Tao Shi, Jia Wei","doi":"10.1200/JCO-24-01619","DOIUrl":"10.1200/JCO-24-01619","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"350-353"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522042","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":"DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish.","authors":"Samuel J Klempner, Mohamad Bassam Sonbol, Zev A Wainberg, Hope Elizabeth Uronis, Vi K Chiu, Aaron James Scott, Syma Iqbal, Mohamedtaki Abdulaziz Tejani, Vincent Chung, Melissa C Stilian, Mathis Thoma, Ying Zhang, Michael H Kagey, Jason Baum, Cynthia A Sirard, Rachel A Altura, Jaffer A Ajani","doi":"10.1200/JCO.24.00410","DOIUrl":"10.1200/JCO.24.00410","url":null,"abstract":"<p><strong>Purpose: </strong>The outcomes of anti-PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study.</p><p><strong>Patients and methods: </strong>Patients had untreated human epidermal growth factor receptor 2-negative aGEAs, RECIST v1.1 measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate organ function. Patients received intravenous DKN-01 300 mg once every 2 weeks, tislelizumab 200 mg once every 3 weeks, oxaliplatin 130 mg/m² once every 3 weeks, and capecitabine 1,000 mg/m² twice daily on days 1-15 of each 21-day cycle. The primary end point was safety and tolerability. Key secondary end points included objective response rate (ORR) by RECISTv1.1, progression-free survival (PFS), and overall survival (OS).</p><p><strong>Results: </strong>Between September 18, 2020, and April 8, 2021, 25 patients were enrolled. All patients who received at least one dose of DKN-01 were included in the safety analysis. Most patients had gastroesophageal junction tumors, median age was 61 years, 76% were male, and 55% were ECOG of 0. All patients reported at least one treatment-emergent adverse event. The ORR was 73% (95% CI, 49.8 to 89.3), with a disease control rate of 95%. The ORR was 90% (95% CI, 55.5 to 99.7) in the DKK1-high tumor patients and 67% (95% CI, 29.9 to 92.5) in the DKK1-low tumor patients. The median PFS was 11.3 months (95% CI, 5.8 to 12.0) and the 12-month PFS rate was 33%. The median OS was 19.5 months (95% CI, 15.2 to 24.4) with a 12-month OS rate of 76% and an 18-month OS rate of 55%.</p><p><strong>Conclusion: </strong>DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801).</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"339-349"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466553","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":"Misleading Reporting of a Negative Randomized Clinical Trial May Affect Clinical Practice.","authors":"Paul de Boissieu, Sylvie Chevret","doi":"10.1200/JCO.24.01104","DOIUrl":"10.1200/JCO.24.01104","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"354-355"},"PeriodicalIF":42.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390899","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}