Ribociclib-Letrozole Combination as an Alternative for Neoadjuvant Chemotherapy in Selected Postmenopausal Patients...

Area of Science:

• Oncology
• Pharmacology

Background:

• Hormone receptor-positive, HER2-negative early-stage breast cancer (BC) treatment often involves neoadjuvant chemotherapy (NAC).
• Cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy offer a potentially less toxic alternative to NAC.

Purpose of the Study:

• To evaluate if neoadjuvant ribociclib plus letrozole (RL) doubles complete cell cycle arrest (CCCA; Ki67 <1%) compared to chemotherapy (CT) in luminal BC.
• To assess pathological response and toxicity as secondary endpoints.

Main Methods:

• Randomized phase II trial in postmenopausal women with early, luminal, HER2-negative, stage II/III BC.
• Neoadjuvant therapy tailored based on Ki67 levels after two weeks of letrozole.
• Patients with Ki67 ≥1% were randomized to RL or standard CT.

Main Results:

• The CCCA in surgical specimens was similar between RL (35.3%) and CT (31.3%) groups (p=0.73).
• No significant differences in Miller and Payne response or pathological complete response (pCR) rates were observed.
• Overall toxicity was higher in the CT group, with more treatment discontinuations due to toxicity in the CT arm compared to the RL arm.

Conclusions:

• Neoadjuvant ribociclib plus letrozole (RL) did not meet the primary endpoint of doubling CCCA but showed comparable pathological response to chemotherapy (CT).
• RL demonstrated a more favorable toxicity profile than CT.
• RL warrants further investigation as a less toxic alternative for neoadjuvant treatment in this patient population.