Fovinaciclib for First-Line Therapy of Advanced Breast Cancer: A Randomized Clinical Trial.
Key Points: Question: Is fovinaciclib plus letrozole or anastrozole effective and safe as first-line treatment in patients with hormone receptor–positive, human epidermal growth factor receptor 2 (ERBB2; formerly HER2)–negative advanced breast cancer? Findings: This phase 3 randomized clinical trial...
| Publicado en: | JAMA Oncology Vol. 12; no. 8; pp. 855 - 863 |
|---|---|
| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
American Medical Association
Aug2026
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=196379887&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 196379887 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23742437 I6NW jtl: JAMA Oncology issn: 23742437 maglogo: N pubinfo: dt: Aug2026 vid: 12 iid: 8 pid: 30 pub: American Medical Association place: Chicago, Illinois artinfo: ui: 196379887 196379887 196379887 10.1001/jamaoncol.2026.1938 196379887 ppf: 855 ppct: 8 formats: tig: atl: Fovinaciclib for First-Line Therapy of Advanced Breast Cancer: A Randomized Clinical Trial. aug: au: Yuan, Peng Liu, Yunjiang Li, Wei Li, Huiping Tong, Zhongsheng Cheng, Jing Zhang, Mingjuan Shan, Jinlu Zhong, Jincai Yi, Tienan Liu, Jian Li, Huihui Huang, Zhen Wu, Jinsheng Ding, Sijuan Li, Liang Zong, Hong Jia, Hongyan Wang, Shusen Wang, Kun affil: Department of Medical Oncology, Chinese Academy of Medical Sciences Cancer Hospital, Beijing, China sug: subj: Hormone Receptor Positive Breast Neoplasms Drug Therapy Aromatase Inhibitors Therapeutic Use Antineoplastic Agents, Combined Therapeutic Use Patient Safety Drug Efficacy Human Male Female Adult Middle Age Aged Aged, 80 and Over China Randomized Controlled Trials Random Assignment Double-Blind Studies Protein Kinase Inhibitors Cyclin-Dependent Kinases Disease-Free Survival Progression-Free Survival Quality of Life Overall Survival Kaplan-Meier Estimator Confidence Intervals Cox Proportional Hazards Model Data Analysis Software Descriptive Statistics Questionnaires Funding Source Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Aged, 80 & over Male Female ab: Key Points: Question: Is fovinaciclib plus letrozole or anastrozole effective and safe as first-line treatment in patients with hormone receptor–positive, human epidermal growth factor receptor 2 (ERBB2; formerly HER2)–negative advanced breast cancer? Findings: This phase 3 randomized clinical trial of 417 patients showed that adding fovinaciclib to first-line letrozole or anastrozole conferred significant and clinically meaningful progression-free survival benefit and consistent improvements in other efficacy outcomes, along with manageable safety and unaffected quality of life. Meaning: These findings support this combination regimen as first-line therapy for patients with hormone receptor–positive, ERBB2-negative advanced breast cancer. This randomized clinical trial evaluates the efficacy and safety of fovinaciclib plus an aromatase inhibitor as first-line treatment for hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer. Importance: Approximately 70% of patients with breast cancer (BC) have hormone receptor–positive, human epidermal growth factor receptor 2 (ERBB2; formerly HER2)–negative disease. Objective: To evaluate the efficacy and safety of fovinaciclib plus an aromatase inhibitor as first-line treatment for hormone receptor–positive, ERBB2-negative advanced BC. Design, Setting, and Participants: This double-blind, phase 3 randomized clinical trial enrolled patients from March 2, 2022, to June 28, 2023, from 63 centers in China. Eligible patients were adult women with hormone receptor–positive, ERBB2-negative advanced BC and no history of systemic therapy for advanced disease. The data cutoff date was June 25, 2024. Data were analyzed from September to October 2024. Intervention: Patients were randomized (1:1) to receive fovinaciclib, 200 mg (orally once daily on days 1 to 21), or placebo plus letrozole, 2.5 mg, or anastrozole, 1 mg (orally once daily on days 1 to 28), in 28-day cycles. Premenopausal or perimenopausal patients also received goserelin, 3.6 mg (subcutaneously on day 1). Main Outcomes and Measures: The primary end point was progression-free survival (PFS) per blinded independent central review (BICR). Secondary end points included other efficacy end points and safety. Exploratory end points included overall survival (OS) and quality of life. Results: Of 417 randomized female patients, the median (range) age was 57.0 (32-84) years. A total of 208 were randomized to the fovinaciclib arm and 209 to the placebo arm. At prespecified interim analysis (median [range] follow-up, 16.6 [0.3-27.8] months), a significantly prolonged median PFS was observed with fovinaciclib compared with placebo (not reached vs 20.2 months [95% CI, 16.4 months to not evaluable]; hazard ratio, 0.55; 95% CI, 0.38-0.77; 1-sided P <.001) per BICR assessments. Consistent PFS benefit was observed in most patient subgroups. Fovinaciclib was also favored across secondary efficacy end points. OS data were immature, with only 40 events (9.6%). The most common treatment-emergent adverse events were hematologic toxic effects, none of which led to serious adverse events or study drug discontinuation. Incidence of discontinuation due to treatment-emergent adverse events was only 1.4% in both arms (3 of 208 receiving fovinaciclib and 3 of 209 receiving placebo). Longitudinal changes in global health status, function domains, and symptom domains of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were similar between the 2 arms. Conclusions and Relevance: In this randomized clinical trial, adding fovinaciclib to first-line aromatase inhibitor conferred significant and clinically meaningful PFS benefit and consistent improvements in other efficacy outcomes, along with manageable safety and unaffected quality of life. Trial Registration: ClinicalTrials.gov Identifier: NCT05439499 pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|