Ribociclib Earns Positive CHMP Opinion in HR+/HER2– Early Breast Cancer

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of ribociclib (Kisqali) in combination with endocrine therapy for the adjuvant treatment of patients with hormone receptor–positive, HER2-negative early breast cancer, at high risk of disease recurrence, including those with node-negative disease.¹

The recommendation for ribociclib in this patient population is based on data from the phase 3 NATALEE trial (NCT03701334), in which treatment with ribociclib plus endocrine therapy decreased the risk of cancer recurrence by 25.1% compared with endocrine therapy alone in patients with stage II and III hormone receptor–positive, HER2-negative early breast cancer (HR, 0.749; 95% CI, 0.628-0.892; P = .0006). Furthermore, the investigative regimen elicited a consistent, clinically meaningful invasive disease-free survival (iDFS) benefit across key prespecified subgroups.

The European Commission will review the recommendation from CHMP, and a final decision regarding the approval is anticipated within approximately 2 months.

“One-third of people diagnosed with stage II breast cancer and more than half of those diagnosed with stage III will unfortunately experience a return of their cancer in the long term, often as metastatic disease,” Peter A. Fasching, MD, professor of translational medicine, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, in Germany, stated in a press release.¹ “If approved, [ribociclib] could provide an effective and tolerable adjuvant treatment option to mitigate the risk of recurrence in a broader patient population, particularly for patients who currently have limited treatment options, including those with high-risk node-negative disease.”

At the 2024 ESMO Congress, investigators shared updated data from the 4-year landmark analysis of NATALEE.² At a median follow-up of 44.2 months in the intent-to-treat population, ribociclib elicited a 3-year iDFS rate of 90.8% vs 88.1% with a nonsteroidal aromatase inhibitor (NSAI) alone. At 4 years, the iDFS rates with ribociclib and a NSAI alone were 88.5% and 83.6%, respectively (HR, 0.715; 95% CI, 0.609-0.840; P <.0001).

This updated analysis showed that iDFS rates continued to favor ribociclib and deepen beyond the 3-year treatment period across all patient subgroups, including those with node-negative disease.¹

In September 2024, the FDA approved adjuvant ribociclib and an aromatase inhibitor in 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, based on data from NATALEE.³

“Today, many people diagnosed with hormone receptor–positive/HER2-negative early breast cancer in Europe lack options beyond endocrine therapy to help reduce their risk of cancer coming back. If approved, [ribociclib] could nearly double the number of patients eligible for CDK4/6 inhibitor adjuvant therapy,” Patrick Horber, MD, president, International, Novartis, stated in the press release.¹ “Together with the recent FDA approval and late-breaking NATALEE data presented at the ESMO Congress, today’s positive CHMP recommendation further reinforces the differentiated profile of [ribociclib] as a new treatment option for a broad population of patients, including those with node-negative disease.”

The global, multi-center, randomized, open-label trial aimed to evaluate the safety and efficacy of adjuvant ribociclib with endocrine therapy—which consisted of a NSAI and goserelin, if applicable—compared with endocrine therapy alone in patients with stage II and III hormone receptor–positive, HER2-negative early breast cancer. The primary end point of the study was iDFS, and a sum of 5,101 patients across 20 countries were randomly assigned in the trial.

With regard to safety, data showed that when ribociclib was given at the 400-mg dose it was well tolerated and primarily associated with low-grade symptomatic adverse effects.

References

1. Novartis receives positive CHMP opinion for Kisqali to help reduce risk of recurrence in people with HR+/HER2- early breast cancer. News release. Novartis. October 18, 2024. Accessed October 18, 2024. https://www.novartis.com/news/media-releases/novartis-receives-positive-chmp-opinion-kisqali-help-reduce-risk-recurrence-people-hrher2-early-breast-cancer
2. Fasching PA, Stroyakovskiy D, Yardley D, et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with HR+/HER2– early breast cancer: 4-year outcomes from the NATALEE trial. Ann Oncol. 2024;35(suppl 2):S1207. doi:10.1016/j.annonc.2024.08.2251
3. FDA approves Novartis Kisqali to reduce risk of recurrence in people with HR+/HER2- early breast cancer. News release. Novartis. September 17, 2024. Accessed October 18, 2024. https://www.novartis.com/news/media-releases/fda-approves-novartis-kisqali-reduce-risk-recurrence-people-hrher2-early-breast-cancer