FDA OKs Adjuvant Ribociclib in Earlier Stage Breast Cancer

The US Food and Drug Administration (FDA) approved ribociclib (Kisqali, Novartis) in combination with an aromatase inhibitor for adult patients with HR-positive, HER2-negative stages II and III breast cancer at high-risk for recurrence following surgery. 

FDA also approved ribociclib and the aromatase inhibitor letrozole packaged together (Kisqali Femara Co-Pack, Novartis) for the same indication. 

A rival cyclin-dependent kinase 4/6 (CDK4/6) inhibitor abemaciclib (Verzenio, Eli Lilly) carries a similar adjuvant indication, but use of this agent requires patients to be lymph node positive.

There’s no such restriction for the new ribociclib indication, which “allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people,” lead investigator Dennis Slamon, MD, a breast oncologist at the University of California, Los Angeles, said in a Novartis press release. 

The new indication joins ribociclib’s previous approval for advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in combination with an aromatase inhibitor or fulvestrant.

The current approval was based on data from the NATALEE trial. NATALEE randomized 5101 patients with early-stage HR-positive, HER2-negative disease to either 400 mg ribociclib with an aromatase inhibitor or to an aromatase inhibitor alone following surgery. 

Invasive disease-free survival at 36 months was 90.7% in the ribociclib arm vs 87.6% with aromatase inhibitor monotherapy (hazard ratio [HR], 0.749; P = .0006). The trial included patients with and without lymph node involvement. 

At 4 years (well beyond NATALEE’s 3-year treatment window), the ribociclib group continued to do better, with an invasive disease-free survival rate of 88.5% vs 83.6% in the control arm.

Overall survival data remain immature, but with a trend towards improved survival in the ribociclib arm (HR, 0.715; P < .0001), according to a recent report from the 2024 European Society for Medical Oncology Congress. 

There were no new safety signals in the trial. Adverse events in the ribociclib group included neutropenia (62.5% overall; 44.3% grade 3/4), liver-related events (26.4% overall; 8.6% grade 3/4), QT prolongation (5.3% overall; 1.0% grade 3/4), and interstitial lung disease/pneumonitis (1.5% overall; 0.0% grade 3/4), according to Novartis.

Ribociclib dosing for the adjuvant indication is lower than for metastatic disease, but patients are on the same schedule — two 200 mg tablets once daily for 21 days followed by 7 days off in 28-day cycles. Treatment continues for 3 years.

Forty-two 200 mg tablets cost about $15,000, according to drugs.com. A patient assistance program is available through Novartis.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.