Ribociclib Plus Aromatase Inhibitor and Ribociclib/Letrozole Co-Pack Approved for Early High-Risk Breast Cancer
Expert Perspectives · Lyn Brook · 2024-09-18
The FDA has granted approval to ribociclib (Kisqali®, Novartis Pharmaceuticals Corporation) with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative stage II and III early breast cancer at high risk of recurrence. In addition, the FDA approved the ribociclib and letrozole co-pack (Kisqali® Femara® Co-Pack, Novartis Pharmaceuticals Corporation) for the same indication.
Why it matters: “Ribociclib has demonstrated a statistically significant overall survival benefit in pre- and postmenopausal patients with HR-positive and HER2-negative advanced breast cancer,” said Dennis Slamon, MD, Chief of the Division of Hematology-Oncology at UCLA, and colleagues, in their published results of the NATALEE trial (NCT03701334), on which approval was based.
What they studied: Efficacy was studied in the phase 3, open-label, multicenter trial which enrolled 5,101 adults with HR-positive, HER2-negative early breast cancer. Included in the trial were patients with any lymph node involvement, excluding those with microscopic nodal involvement. If there was no nodal involvement, those with either tumor size >5 cm or tumor size 2 to 5 cm with either grade 2 or grade 3 were included.
Patients were randomized 1:1 to receive either 400 mg of ribociclib plus a non-steroidal aromatase inhibitor (NSAI) or an NSAI alone. Participants could receive goserelin as indicated. Key stratification criteria included anatomic stage, prior chemotherapy (neoadjuvant versus adjuvant), menopausal status (premenopausal and males versus postmenopausal), and region (North American/Western Europe/Oceania versus the rest of the world).
The primary efficacy outcome measured was invasive disease-free survival (iDFS), defined as time from randomization to the first occurrence of local or regional invasive breast recurrence, distant recurrence, death from any cause, contralateral invasive breast cancer, or secondary primary non-breast invasive cancer, excluding basal and squamous cell carcinoma of the skin.
What they found: At an interim analysis, the intent-to-treat patient population saw a statistically significant improvement in iDFS. At the final analysis of iDFS, efficacy at 36 months was 90.7% in those receiving ribociclib plus an NSAI compared with 87.6% in those receiving an NSAI alone. Overall survival was immature at the time of iDFS final analysis.
Adverse events: The adverse events experienced in the NATALEE trial were consistent with the current safety profile for ribociclib in combination with NSAI. Please see the prescribing information for additional safety information.
Conclusion: “The 36-month treatment duration of ribociclib in NATALEE is extended compared with that in other adjuvant cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor trials and is intended to maximize efficacy due to longer duration of CDK4/6 inhibition,” concluded Dr. Slamon and colleagues. “Compared with the 600 mg per day dose used in advanced breast cancer, the reduced ribociclib dose used in NATALEE may improve tolerability while maintaining efficacy.”
Instructions: In the adjuvant treatment setting, the recommended dosage of ribociclib is 400 mg, taken orally, once daily as two 200 mg film-coated tablets for 21 consecutive days followed by 7 days off in 28-day treatment cycles. Refer to the prescribing information for the recommended dosage of the aromatase inhibitor.
Additionally, ribociclib has updated storage conditions; ribociclib should now be refrigerated until dispensed to patients, and patients should be advised to store ribociclib at room temperature for up to two months upon dispensing.