Key Points
• In the current study published in Breast, Italian researchers compared endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) for the treatment of 717 patients with luminal-metastatic breast cancer (MBC) to determine the best first-line (1L) and second-line (2L) options for treatment.
• The authors specified the following clinical practice points:
“First-line (1st L) CDK4/6i-based therapies represent the standard treatment in luminal mBC. However, prospective head-to-head comparisons are still lacking for many 1st line options, and it is still crucial to define the best treatment strategy for both 1st and 2nd L.
“The present study confirmed the significant impact of 1st L CDK4/6i-based therapies on a homogeneous real-world cohort. Moreover, the study suggested a preeminent role for ET after first-line CDK4/6i [CDK 4/6 Inhibitors], supporting the concept of an ET switch to overcome potential resistance mechanisms and restore clinical response.
“The second-line ET, combined with other targeted molecules, might potentially represent a feasible option after CDK4/6i failure, allowing to further postpone CT to later lines.”
• Overall, the study bolsters the hypothesis that 2L ET plus other targeted molecules could serve as a treatment alternative following CDK4/6i failure, thus delaying CT to later lines.
• Strengths of the current study include its use of real-world data, which has been an emerging focus of randomized trials. Limitations include the study’s lower power, with fewer patients administered CDK 4/6 Inhibitors. Moreover, selection bias in clinical decision-making could have resulted from factors including age, progression survival, prior toxicities, potential adherence to treatment, previous treatment route of administration, and time to progression.