Ribociclib Recognized by NCCN Clinical Practice Guidelines as Category 1 Preferred Breast Cancer Adjuvant Treatment

The National Comprehensive Cancer Network (NCCN) Guidelines in Oncology for breast cancer now recommends ribociclib (Kisqali; Novartis) as a Category 1 preferred cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) adjuvant therapy in combination with an aromatase inhibitor (AI) for patients who have hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC). Currently, ribociclib is the only CDK4/6i that is recommended for both all node-positive disease in addition to patients without nodal involvement with high-disease characteristics, such as tumors larger than 5 cm, or for tumors sized 2 to 5 cm, either with grade 2 with high genomic risk/Ki-67 of 20% or more, or grade 3.¹

Image credit: CozyDigital | stock.adobe.com

According to NCCN, a Category 1 recommendation indicates high levels of clinical evidence and uniform consensus among NCCN on ribociclib as an appropriate treatment for this patient population. The recommendation comes after the presentation of longer-term results from the phase 3 NATALEE trial (NCT03701334) at the European Society for Medical Oncology 2024 Congress, which demonstrated a deepening efficacy benefit even beyond the ribociclib treatment duration in a broad population with patients, including those with node-negative disease and in EBC indications.^1,2

Ribociclib is a selective cyclin-dependent kinase inhibitor, and it slowed the progression of cancer by inhibiting 2 proteins, CDK4 and CDK6. When over-activated, these 2 proteins can allow cancer cells to grow and divide quickly, and targeting CDK4/6 with enhanced precision can help play a role in ensuring cancer cells do not continue to replicate uncontrollably. The tablet is administered orally for 3 weeks, followed by 1 week off the treatment, in combination with any 4 weeks of any AI.^1,3

Further, ribociclib in combination with an AI for the treatment of HR+/HER2- stage 2 and 3 EBC at a high risk of recurrence was approved by the FDA in September 2024. This approval came after data presented at the ESMO 2024 Congress which showed a clinically meaningful reduction in the risk of disease recurrence as well as well-tolerated safety.³

NATALEE (NCT03701334) is a global, open-label, multicenter phase 3 trial that enrolled over 1500 adult patients with HR+/HER2- EBC. They were randomly assigned to receive ribociclib in combination with endocrine therapy (ET) as an investigational adjuvant treatment versus ET monotherapy. The adjuvant ET in both treatment arms was a non-steroidal AI (NSAI; anastrozole or letrozole) and goserelin, if applicable. The study’s primary end point was invasive disease-free survival benefit as defined by the Standardized Definitions for Efficacy End Points.³

According to the data, ribociclib with ET demonstrated an approximate 25.1% reduction in risk of disease recurrence compared with ET alone, including those with high-risk node-negative disease (HR = 0.749; 95% CI: 0.628, 0.892; P = .0006). In addition, the investigators had also observed a deepening benefit beyond 3 years as well as a 28.5% risk of recurrence in patients receiving the ribociclib regimen (HR = 0.715; CI 95% 0.609-0.840; P < .0001).³ Further, the updated NCCN guidelines will approximately double the number of patients who could benefit from treatment with a CDK4/6i in the adjuvant setting, according to experts.¹

“These evidence-based guidelines are helpful to clinicians when determining optimal treatment options for patients,” Shreeram Aradhye, MD, president of development and chief medical officer at Novartis, said in a news release. “Importantly, the NCCN Guideline recommendation of ribociclib in this broad population reaffirms the importance of offering eligible patients with early breast cancer, including those with limited nodal involvement and high-risk N0 disease, a CDK4/6i treatment like ribociclib in addition to endocrine therapy to reduce their risk of recurrence.”¹

REFERENCES

1. Novartis. Novartis ribociclib (Kisqali) recognized as Category 1 preferred breast cancer adjuvant treatment by NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). News release. October 24, 2024. Accessed October 25, 2024. https://www.novartis.com/news/media-releases/novartis-ribociclib-kisqali-recognized-category-1-preferred-breast-cancer-adjuvant-treatment-nccn-clinical-practice-guidelines-oncology-nccn-guidelines

2. National Comprehensive Cancer Network — Home. NCCN. Accessed October 25, 2024. https://www.nccn.org/

3. Gerlach, A. FDA Approves Ribociclib in Combination With an Aromatase Inhibitor for HR+/HER2- Early Breast Cancer. Pharmacy Times. September 17, 2024. Accessed October 25, 2024. https://www.pharmacytimes.com/view/fda-approves-ribociclib-in-combination-with-an-aromatase-inhibitor-for-hr-her2--early-breast-cancer