The hormone receptor-postivie (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) market has seen promising results with the advent of cyclin dependent kinase 4/6 (CDK4/6) inhibitors in recent years. These inhibitors, when used in combination with endocrine therapies (ET), have had extensive clinical success in extending survival benefit in the first-line treatment of HR+/HER2- metastatic BC. Results from the phase III NATALEE (n=5101) trial for Novartis’ Kisqali (ribociclib) were presented at the European Medical Society of Oncology (ESMO) 2023 congress. The trial results lend weight to the implementation of Kisqali in treatment for early breast cancer patients, says GlobalData, a leading data and analytics company.

According to GlobalData, the HR+/HER2- early breast cancer market is dominated by Pfizer’s Ibrance (palbociclib), which saw global sales of $5.1 billion in 2022, while Eli Lily’s Verzenio (abemaciclib) achieved $2.5 billion, double that of Kisqali.

Thomas Wales, Oncology Analyst at GobalData, comments: “With recent expansions to Verzenio’s label now encompassing HR+/HER2- early BC, it has become critical for Kisqali to demonstrate early efficacy in breast cancer to remain in the competitive landscape for the therapy area.”

Although CDK4/6 inhibitors represent a significant market share for HR+/HER2- BC, this market will see some disruption due to Ibrance’s patent expiring towards the end of the decade. External competitors, such as AstraZeneca’s Enhertu (trastuzumab deruxatecan), are also being investigated in the Phase III trial DESTINY-Breast04 for use in HER2-low expressing BC patients, which will further put pressure on Kisqali’s performance.

Wales continues: “The NATALEE trial assessed the efficacy of Kisqali in combination with non-steroidal aromatase inhibitors (NSAI) vs NSAI alone. The invasive disease-free survival (iDFS) benefit was longer with Kisqali and endocrine therapy compared to endocrine therapy alone (HR 0.748, P=0.0014).”

Kisqali also benefits from strong guideline recommendations, with a category 1 assignment from the National Comprehensive Cancer Network, as well as a score of 5 with ESMO-MCBS scorecards, making it the only CDK4/6 inhibitor to achieve this. Furthermore, matched-adjusted indirect comparisons between Kisqali’s MONALEESA-2 and Verzenio’s MONARCH-3 clinical trials have found that time to sustained deterioration significantly favoured Kisqali + NSAI in appetite loss, diarrhea, fatigue, and arm symptoms. This would indicate that the overall quality of life is superior for patients receiving a Kisqali + NSAI combination compared to Verzenio + NSAI.

Wales concludes: “With these clinical features and guidance recommendations, Kisqali still remains a competitive option for prescribers in the therapy area. Despite this, Kisqali will likely not overtake Verzenio’s position due to its already existing early BC indication and its familiarity with prescribers.”