Ribociclib With Nonsteroidal Aromatase Inhibitor Does Not Reduce Quality of Life in HR+/HER2- Early Breast Cancer

Adding adjuvant ribociclib (Kisqali; Novartis) to a nonsteroidal aromatase inhibitor (NSAI) does not negatively affect health-related quality of life (HRQOL) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) early breast cancer (eBC), according to HRQOL data from the NATALEE trial (NCT03701334).¹

3D visualization of cancer cells | Image Credit: © Best - stock.adobe.com

In the United States, over 300,000 women will receive a BC diagnosis in 2024, which will result in over 42,000 deaths, according to the American Cancer Society. Close to 70% of all new cases of BC are of the most prevalent subtype, HR+/HER2. Because patients with HR+/HER2- BC have a significant chance of their cancer returning, usually as incurable metastatic illness, effective treatments that prevent disease recurrence are essential.²

Ribociclib is a cyclin-dependent kinase inhibitor that selectively inhibits CDK4/6, or cyclin-dependent kinase 4 and 6. Excessive activation of these proteins can promote the rapid development and multiplication of cancer cells, preventing them from proliferating further. With 4 weeks of any aromatase inhibitor, ribociclib is given orally as a pill for 3 weeks, followed by a week off from therapy. Two 200-mg tablets containing 400 mg showed good safety and good tolerance in the NATALEE trial.²

In the global phase 3 multicenter, open-label trial, over 1500 persons with HR+/HER2- eBC from 20 different countries were randomly assigned to receive ET monotherapy or ribociclib in conjunction with ET as an experimental adjuvant treatment. Patients receiving ribociclib with ET, including those with high-risk node-negative disease, had a 25.1% (HR = 0.749; 95% CI, 0.628, 0.892; P = .0006) lower risk of disease recurrence when compared to ET alone, according to the findings. Researchers also found a 28.5% chance of recurrence (HR = 0.715; 95% CI, 0.609-0.840; P < .0001) and a deeper advantage after 3 years.²

In the study published in Clinical Cancer Research, investigators reported the HRQOL results from the trial. Patient-reported outcomes were scored using multiple questionnaires and surveys, including the European Organization for Research and Treatment of Cancer core quality of life questionnaire covering global health status and physical, social, and emotional functioning domains; the supplementary European Organization for Research and Treatment of Cancer breast cancer–specific QOL questionnaire breast symptoms scale; health on a visual analog scale of the generic EuroQOL 5-level instrument; and the Hospital Anxiety and Depression Scale. Physical functioning was the main HRQOL end point. HRQOL changes during treatment were assessed using mean scores and predefined linear-time repeated-measure and time-categorical models.³

The researchers evaluated HRQOL in all patients in the ribociclib plus NSAI (n = 2549) and NSAI alone (n = 2552) treatment arms. Patients in both arms achieved statistically significant rates of compliance at approximately 93% to as high as 97%. The mean scores for all analyzed domains did not differ meaningfully from baseline throughout the treatment period. Similarly, no clinically significant changes from baseline were observed in either treatment arm, nor were there any notable differences between the 2 arms in the model-adjusted, time-categorical mean scores for any HRQOL domains.³

These findings were assessed using published thresholds for interpreting longitudinal and between-group differences, with all values remaining within 0.5 standard deviations of their respective baseline values. A linear-time regression analysis further confirmed the consistency of these results.³

The reported HRQOL data further supports the safety, efficacy, and favorability of ribociclib plus an aromatase inhibitor. Treatment sequencing continues to be a challenge in cancer care, but these data offer health care providers more clarity when utilizing this combination therapy in patients with HR+/HER2- eBC.

REFERENCES

1. A trial to evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/​HER2- early breast cancer (NATALEE). ClinicalTrials.gov Identifier: NCT03701334. Updated October 3, 2023. Accessed April 22, 2025. https://clinicaltrials.gov/study/NCT03701334

2. FDA approves ribociclib in combination with an aromatase inhibitor for HR+/HER2- early breast cancer. Pharmacy Times. September 17, 2024. Accessed April 22, 2025. https://www.pharmacytimes.com/view/fda-approves-ribociclib-in-combination-with-an-aromatase-inhibitor-for-hr-her2--early-breast-cancer

3. Fasching P, Slamon D, Nowecki Z, et al. Health-Related quality of life in patients with HR+/HER2− early breast cancer treated with ribociclib plus a nonsteroidal aromatase inhibitor: Results from the NATALEE trial. Clin Cancer Res. March 28, 2025. doi.org/10.1158/1078-0432.CCR-24-1724