Lessons From the SONIA Trial on Timing of CDK4/6 Inhibitors in Advanced Breast Cancer—The Sooner, the Better?
Mené sur 1 050 patientes atteintes d'un cancer du sein HR+ ERBB2- de stade avancé (âge médian : 64 ans ; durée médiane de suivi : 58,5 mois), cet essai randomisé de phase III compare l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité d'inhibiteurs de CDK4/6 dispensés en première ou en deuxième ligne
Patients with advanced breast cancer have a growing armamentarium of treatment options, and nearly all will receive multiple lines of treatment.1-3 On average, response rates and median times to progression are higher in first-line than in second-line, and in second-line than in third-line, and so forth, though clinical experience shows that outcomes for individual patients are quite variable. Many drugs are approved based on initial studies of treatment-resistant cancer, and then are studied again to see if utilization earlier in the course of advanced cancer would also be effective. As more treatment options enter routine clinical practice, there are important, practical questions about the optimal sequencing of agents and questions about when in the sequence of therapy drugs should be deployed to maximal utility. There are potential clinical benefits to earlier utilization of active, important agents. Drugs might be more efficacious in an earlier line of therapy owing to tumor biology or therapeutic resistance or might have salutary clinical outcomes such as preserving quality of life for longer arcs of time, delaying the time to initiation of agents that have more adverse events, or improving overall survival (OS). There are also commercial implications to the timing of drug utilization, as treatment durations are typically longer in earlier lines of treatment. Finally, there are concerns that delaying initiation of an important drug might forfeit the opportunity for treatment if the patient cannot receive additional lines of therapy.4 Yet despite these compelling reasons to study the optimal sequencing of treatments, few clinical trials are designed to address such questions once drugs have secured regulatory approval.
JAMA Oncology , éditorial, 2026