Photo Credit: Mohammed Haneefa Nizamudeen
Adjuvant ribociclib, a CDK4/6 inhibitor, combined with an aromatase inhibitor significantly improved invasive disease-free survival (iDFS) at 3 years in patients with HR-positive/HER2-negative early breast cancer (eBC) with high risk for recurrence leading to its FDA approval. Interestingly, the adjuvant dose in the phase 3 NATALEE trial was lower than the approved dose for the metastatic setting and promising for future dose-reduction studies.
Ribociclib has demonstrated significant improvements in progression-free survival and overall survival (OS) in advanced breast cancer1. The phase 3 NATALEE trial (NCT03701334) aimed to investigate the addition of ribociclib to endocrine therapy in HR-positive/HER2-negative eBC at high risk for recurrence. Jennifer Gao, MD, CDER, US Food and Drug Administration, presented the final iDFS analysis of the NATALEE trial and shared insights into the regulatory considerations for using adjuvant ribociclib to treat this patient population2.
A total of 5,101 participants were randomly assigned in a 1:1 ratio to receive adjuvant treatment with ribociclib (400 mg/day for 3 years) plus an aromatase inhibitor or an aromatase inhibitor alone (for at least 5 years). Adding ribociclib to adjuvant endocrine therapy significantly improved iDFS at 3 years: 90.7% versus 87.9% (HR 0.749; 95% CI 0.63–0.89; P=0.0014). The OS results showed a trend toward favoring the addition of ribociclib (HR 0.89; 95% CI 0.66–1.20) but are considered immature. Overall safety signals were consistent with the safety profile of ribociclib.
The attendants noted that the dose of ribociclib (400 mg) in this trial was lower than the approved starting dose (600 mg) for metastatic disease2,3. The trial design was commended, as these data encourage future dose-reduction studies in specific patient groups, rather than using the maximum tolerated dose.
“We expect the benefit to be meaningful and believe that the results will provide an additional treatment option for patients with early breast cancer at high risk for recurrence,” concluded Dr. Gao.
Medical writing support was provided by Kulsoom Abdul.
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