Adjuvant Ribociclib Wins EU Approval for HR+/HER2– Early Breast Cancer

Adjuvant ribociclib plus endocrine therapy was approved in Europe for HR-positive/HER2-negative early breast cancer at high risk of recurrence.

The European Commission has approved ribociclib (Kisqali) in combination with an aromatase inhibitor (AI) for the adjuvant treatment of patients with hormone receptor–positive, HER2-negative early breast cancer at high risk of recurrence.1

The regulatory decision was supported by data from the phase 3 NATALEE trial (NCT03701334). Findings published in the New England Journal of Medicine showed the combination (n = 2549) reduced the risk of invasive disease, recurrence, or death by 25% compared with endocrine therapy alone (n = 2552; HR, 0.75; 95% CI, 0.62-0.91; P = .003).2 At a median follow-up of 27.7 months, patients treated with ribociclib plus an AI achieved an estimated 3-year invasive disease–free survival (iDFS) rate of 90.4% compared with 87.1% for those given an AI alone.

“For many patients diagnosed with stage II or III hormone receptor–positive/HER2-negative early breast cancer, the risk of their cancer coming back despite treatment with endocrine therapy remains high, even after decades,” Michael Gnant, MD, FACS, FEBS, professor of surgery at the Medical University of Vienna in Austria and president of the Austrian Breast and Colorectal Study Group, stated in a news release.1 “This approval represents a positive milestone for the early breast cancer community in Europe, including physicians who now have a new option to help reduce the risk of recurrence in a broader population of patients.”

In September 2024, the FDA approved adjuvant ribociclib plus an AI for the treatment of patients with hormone receptor–positive, HER2-negative stage II and III early breast cancer at high risk of recurrence, including those with node-negative disease.3 That decision was also based on data from NATALEE.

The international, open-label, NATALEE trial enrolled patients at least 18 years of age with histologically confirmed stage II or III hormone receptor–positive, HER2-negative early breast cancer per local assessment.2 Patients with stage IIB or III disease were allowed to enroll irrespective of nodal status; those with stage IIA disease needed to have involvement of at least 1 lymph node. Notably, patients with grade 2 tumors without nodal involvement who had a Ki-67 proliferation index of at least 20% or high-risk genomics were allowed to participate.

Any neoadjuvant or adjuvant endocrine therapy was allowed for up to 12 months prior to randomization. Prior treatment with a CDK4/6 inhibitor was not allowed.

Patients were randomly assigned 1:1 to receive ribociclib at 400 mg once per day for the first 21 days of each 28-day cycle for up to 36 months in combination with an AI or an AI alone. Stratification factors included stage (II vs III), menopausal status (premenopausal women and men vs postmenopausal women), previous neoadjuvant/adjuvant chemotherapy (yes vs no), and location (North America, Western Europe, and Oceania vs rest of the world).

The trial’s primary end point was iDFS. Key secondary end points included distant disease–free survival (DDFS), recurrence-free survival (RFS), overall survival (OS), safety, and quality of life.

Additional data demonstrated that the 3-year DDFS rate was 90.8% for the ribociclib arm vs 88.6% for the control arm (HR, 0.74; 95% CI, 0.60-0.91). The 3-year RFS rates were 91.7% and 88.6%, respectively (HR, 0.72; 95% CI, 0.58-0.88).

At a median follow-up of 30 months for OS, 2.4% of patients in the experimental arm had died compared with 2.9% of patients in the control arm (HR, 0.76; 95% CI, 0.54-1.07).

Regarding safety, any-grade adverse effects (AEs) occurred in 97.9% of patients treated with the ribociclib regimen vs 87.1% of patients who received AI monotherapy. The rates of serious AEs were 13.3% and 9.9%, respectively. AEs led to the discontinuation of ribociclib in 18.9% of patients and the discontinuation of both ribociclib and an AI in 3.3% of patients. The rates of patients who discontinue an AI for any cause were similar between the 2 arms.

The most common any-grade AEs included neutropenia (ribociclib arm, 62.1%; control arm, 4.5%), arthralgia (36.5%; 42.5%), and liver-related AEs (25.4%; 10.6%). The most common grade 3 or higher AE was neutropenia, which was reported in 43.8% of patients in the experimental arm vs 0.8% of patients in the control arm.

"Breast cancer recurrence can be a lifelong concern for those living with the disease. Patients deserve access to treatment options that help minimize the risk of their cancer coming back and put their mind at ease,” Iris Zemzoum, MD, president, Europe, Novartis, added in a news release.1 “We are proud of this approval, which will help to address a key unmet need and improve health outcomes for a broader population of patients in Europe.

References

  1. Novartis Kisqali receives European Commission approval in a broad population of patients with HR+/HER2- early breast cancer at high risk of recurrence. News release. Novartis. November 27, 2024. Accessed November 27, 2024. https://www.novartis.com/news/media-releases/novartis-kisqali-receives-european-commission-approval-broad-population-patients-hrher2-early-breast-cancer-high-risk-recurrence
  2. Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 2024;390(12):1080-1091. doi:10.1056/NEJMoa2305488
  3. FDA approves ribociclib with an aromatase inhibitor and ribociclib and letrozole co-pack for early high-risk breast cancer. FDA. September 17, 2024. Accessed November 27, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ribociclib-aromatase-inhibitor-and-ribociclib-and-letrozole-co-pack-early-high-risk-0