Radiological Complete Response as a Prognostic Marker in HR-positive Metastatic Breast Cancer Treated With CDK4/6 Inhibitors: Implications for Treatment De-escalation.

[BACKGROUND/AIM] Endocrine therapy combined with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) is standard first-line treatment for hormone receptor (HR)-positive metastatic breast cancer (MBC). Although radiological complete response (rCR) is rarely achieved, the optimal management of such patients remains unclear. In human epidermal growth factor receptor 2 (HER2)-positive MBC, discontinuation of anti-HER2 therapy after rCR has been explored but treatment de-escalation in HR-positive MBC has not been sufficiently investigated.

[PATIENTS AND METHODS] We retrospectively analyzed 178 patients with HR-positive MBC treated with CDK4/6i-based endocrine therapy at our Institution between December 2017 and October 2024. Clinicopathological factors, including immune-related markers (absolute lymphocyte count and neutrophil-to-lymphocyte ratio), were evaluated for associations with rCR. Bone metastases were considered rCR-equivalent only if radiological stability was maintained for ≥6 months. Patients who discontinued CDK4/6i after achieving rCR were further assessed.

[RESULTS] Nineteen patients (10.7%) achieved rCR (13 with measurable non-bone metastases and six with bone metastases). The median time to rCR was 11.9 months. rCR occurred more frequently in patients treated with abemaciclib (=0.008) and those with smaller primary tumors (≤2 cm, =0.040). Earlier-line treatment also showed a trend towards achieving higher rCR rates (=0.104). Among the 19 patients with rCR, five discontinued CDK4/6i while maintaining endocrine therapy. Fatigue and diarrhea improved after discontinuation. Two patients experienced disease progression after 14.5 and 20.5 months of CDK4/6i withdrawal, respectively.

[CONCLUSION] rCR following CDK4/6i therapy was an independent prognostic factor in HR-positive MBC. Patients with smaller primary tumors and early administration of abemaciclib were more likely to achieve rCR. Selected patients achieving rCR may be candidates for discontinuation of CDK4/6i as part of individualized treatment de-escalation strategies.