Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer

• 成果类型: Article
• 署名作者: Sonke, Gabe S.; van Ommen-Nijhof, Annemiek; Wortelboer, Noor; van der Noort, Vincent; Swinkels, Astrid C. P.; Blommestein, Hedwig M.; Paez, Cristina Guerrero; Mol, Linda; Beeker, Aart; Beelen, Karin; Hamming, Lisanne C.; Heijns, Joan B.; Honkoop, Aafke H.; de Jong, Paul C.; van Rossum-Schornagel, Quirine C.; van Schaik-van de Mheen, Christa; Tol, Jolien; Tromp-van Driel, Cathrien S.; Vrijaldenhoven, Suzan; van Leeuwen-Stok, A. Elise; Konings, Inge R.; Jager, Agnes; de Jong, Paul C.
• 署名单位: Netherlands Cancer Institute; Erasmus University Rotterdam; Erasmus MC; Erasmus MC Cancer Institute; Netherlands Cancer Institute; Erasmus University Rotterdam - Excl Erasmus MC; Erasmus University Rotterdam; Spaarne Hospital; Rijnstate Hospital; Medical Center Leeuwarden; Amphia Hospital; Isala Clinics; St. Antonius Hospital Utrecht; Franciscus Gasthuis; Meander Medisch Centrum; Jeroen Bosch Ziekenhuis; Gelre Hospitals; Medical Center Of Alkmaar; Vrije Universiteit Amsterdam; University of Amsterdam
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5751
• DOI: 10.1038/s41586-024-08035-2
• 发表日期: 2024-12-12
• 页码: 474-+
• 关键词: plus fulvestrant; survival; palbociclib; combination; letrozole; alpelisib

摘要

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) in combination with endocrine therapy improve the outcomes of patients with hormone-receptor (HR)-positive, HER2-negative advanced breast cancer and can be used early as first-line treatment or deferred to second-line treatment(1-7). Randomized data comparing the use of CDK4/6i in the first- and second-line setting are lacking. The phase 3 SONIA trial (NCT03425838) randomized 1,050 patients who had not received previous therapy for advanced breast cancer to receive CDK4/6i in the first- or second-line setting(8). All of the patients received the same endocrine therapy, consisting of an aromatase inhibitor for first-line treatment and fulvestrant for second-line treatment. The primary end point was defined as the time from randomization to disease progression after second-line treatment (progression-free survival 2 (PFS2)). We observed no statistically significant benefit for the use of CDK4/6i as a first-line compared with second-line treatment (median, 31.0 versus 26.8 months, respectively; hazard ratio = 0.87; 95% confidence interval = 0.74-1.03; P = 0.10). The health-related quality of life was similar in both groups. First-line CDK4/6i use was associated with a longer CDK4/6i treatment duration compared with second-line use (median CDK4/6i treatment duration of 24.6 versus 8.1 months, respectively) and more grade >= 3 adverse events (2,763 versus 1,591, respectively). These data challenge the need for first-line use of a CDK4/6i in all patients.