Journal Article

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

Jager, Agnes, van Rossum-Schornagel, Quirine C., Tol, Jolien, van Leeuwen-Stok, A. Elise, Beeker, Aart, van Schaik-van de Mheen, Christa, Sonke, Gabe S., Beelen, Karin, Heijns, Joan B., van der Noort, Vincent, Tromp-van Driel, Cathrien S., van Ommen-Nijhof, Annemiek, de Jong, Paul C., Vrijaldenhoven, Suzan, Konings, Inge R., Hamming, Lisanne C., Honkoop, Aafke H., Swinkels, Astrid C. P., Guerrero Paez, Cristina, Blommestein, Hedwig M., Wortelboer, Noor, Mol, Linda

2024

Overview

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 , 2 , 3 , 4 , 5 , 6 – 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. The phase 3 SONIA trial challenges the benefits of using cyclin-dependent kinase 4 and 6 inhibitors as a first-line compared with second-line treatment.

• Publisher: Nature Publishing Group UK
• Subject: 631/67/1347 / 692/308/2779/777 / Aged / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Antineoplastic Agents, Hormonal - administration & dosage / Antineoplastic Agents, Hormonal - pharmacology / Antineoplastic Agents, Hormonal - therapeutic use / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Aromatase Inhibitors - administration & dosage / Aromatase Inhibitors - pharmacology / Aromatase Inhibitors - therapeutic use / Breast Neoplasms - classification / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Cyclin-Dependent Kinase 4 - antagonists & inhibitors / Cyclin-Dependent Kinase 4 - metabolism / Cyclin-Dependent Kinase 6 - antagonists & inhibitors / Cyclin-Dependent Kinase 6 - metabolism / Disease Progression / Estrogen Receptor Antagonists - administration & dosage / Estrogen Receptor Antagonists - pharmacology / Estrogen Receptor Antagonists - therapeutic use / Female / Fulvestrant - administration & dosage / Fulvestrant - therapeutic use / Humanities and Social Sciences / Humans / Middle Aged / multidisciplinary / Neoplasm Staging / Progression-Free Survival / Protein Kinase Inhibitors - administration & dosage / Protein Kinase Inhibitors - pharmacology / Protein Kinase Inhibitors - therapeutic use / Quality of Life / Science / Science (multidisciplinary) / Time-to-Treatment