NATALEE Trial: Quality of Life Maintained for Many Patients Treated With Ribociclib for Early-Stage Breast Cancer

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An analysis of patient-reported outcomes in the adjuvant phase III NATALEE trial of ribociclib plus endocrine therapy in early-stage breast cancer showed maintenance of health-related quality of life (QOL), as determined by a number of factors. For patients receiving the inhibitor of cyclin-dependent kinase 4 and 6 (CDK4/6), scores for physical functioning and global health status were similar to those of patients treated with endocrine therapy alone, over the duration of the study, Peter A. Fasching, MD, of the University Hospital Erlangen Comprehensive Cancer Center and Friedrich-Alexander University Erlangen-Nuremberg, Germany, reported at the September 2023 European Society for Medical Oncology (ESMO) Virtual Plenary.1

“Especially in the adjuvant setting, the impact of treatment on quality of life provides some guidance for clinical decision-making.”
— Peter A. Fasching, MD

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All three MONALEESA trials in metastatic breast cancer found that health-related QOL was maintained or improved with the addition of ribociclib to endocrine therapy. Dr. Fasching’s presentation focused on health-related QOL findings for the early-stage breast cancer population. He noted the importance of the findings for that population: “Especially in the adjuvant setting, the impact of treatment on quality of life provides some guidance for clinical decision-making.”

As reported by Dennis J. Slamon, MD, PhD, at the 2023 ASCO Annual Meeting,2 the 5,101-patient phase III NATALEE trial demonstrated a statistically significant invasive disease–free survival benefit for ribociclib plus endocrine therapy given for 3 years to patients with early-stage

Dennis J. Slamon, MD, PhD

Dennis J. Slamon, MD, PhD

breast cancer (hazard ratio [HR] = 0.748; P = .0014). Patients received ribociclib plus a nonsteroidal aromatase (letrozole or anastrozole), and a luteinizing hormone–releasing hormone (LHRH) agonist for premenopausal women and men, vs the aromatase inhibitor alone (and LHRH agonist), in a broad population of patients with early stage II or III hormone receptor–positive, HER2-negative tumors that were node-positive or node-negative with other high-risk features.

Assessment of Health-Related Quality of Life in NATALEE

The investigators obtained patient-reported outcomes based on a number of survey instruments: the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality-of-Life questionnaire) for function (physical, social, and emotional) and global health status; EORTC QLQ-BR23 for breast cancer symptoms; the EQ-VAS (Euro-QoL visual analog scale) of the EQ-5D-5L instrument; and the Hamilton Anxiety and Depression Scale.

They assessed outcomes using two types of analyses: a descriptive analysis showing the change from baseline as mean summaries of scores and a repeated measures regression model that adjusted for stratification factors, baseline score, treatment time, and treatment-time interaction—creating a prespecified regression analysis that assessed outcomes over time.

Patients were scheduled for multiple assessments: at screening; every 12 weeks for the first 2 years; every 24 weeks after the first 2 years; at the end of treatment; at confirmation of first recurrence; and every 12 weeks or 24 weeks after confirmation of distant recurrence. Physical functioning was the prespecified primary patient-reported outcome. The outcome for all was change in scores from baseline. Approximately 97% of patients on treatment completed the surveys.

The analysis was conducted after a median follow-up of 34 months. At that time, 20% of patients had completed 3 years of ribociclib plus endocrine therapy.

Key Findings

At baseline, all patient-reported outcomes measures were almost identical for the two arms of NATALEE. The key findings over time from the patient-reported outcomes analyses are listed here:

  • Physical functioning was maintained with the addition of ribociclib to standard-of-care endocrine therapy; outcomes were not impacted by the treatment arm.
  • Global health status was not impacted over time in either arm.
  • Social functioning over time did not differ from baseline in either arm.
  • Emotional functioning deteriorated to a small degree from baseline in both arms; no differences were seen between the arms.
  • Breast cancer symptoms were reduced quickly from baseline, and then they slowly improved over the study, with no differences between the arms.
  • The visual analog scale changed appreciably over time in either arm.
  • Anxiety scores and depression scores did not change meaningfully over time in either arm.

Dr. Fasching elaborated on these findings: “For physical functioning, global health status, and visual analog scale, both arms experienced a similar decrease from baseline at the first assessment. After the initial drop, the curves stabilized, with a 1-point average difference between the experimental and control arms. Regression analysis confirmed consistent health-related QOL between the arms over time, adjusted for stratification factors (eg, menopausal status, stage, prior neo[adjuvant] chemotherapy, and geographic region). Premenopausal patients vs postmenopausal patients and patients with prior (neo)adjuvant chemotherapy, vs no prior chemotherapy, tended to have higher physical functioning.


  • In the phase III NATALEE trial, the addition of ribociclib to endocrine therapy significantly reduced invasive disease–free survival events by 25%.
  • In a new analysis, investigators reported that health-related quality of life was maintained throughout the duration of treatment.
  • Scores on a variety of measures did not significantly differ from those of patients treated with endocrine therapy alone.

“Taken together with the NATALEE efficacy data, the health-related patient-reported outcomes further support the risk-benefit profile for the addition of ribociclib to a nonsteroidal aromatase inhibitor in a broad population of patients with stage II or III hormone receptor–positive, HER2-negative early breast cancer at risk of recurrence,” Dr. Fasching concluded. 

DISCLOSURE: Dr. Fasching reported financial relationships with Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck Sharp & Dohme, AstraZeneca, Hexal, Eli Lilly, Pierre Fabre, Seagen, Agendia, Gilead Sciences, Sanofi Aventis, and BioNTech.


1. Fasching PA, Slamon D, Nowecki Z, et al: Health-related quality of life in the phase III NATALEE study of adjuvant ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) vs NSAI alone in patients with HR+/HER2− early breast cancer. ESMO Virtual Plenary. Abstract VP3-2023. Presented September 14, 2023.

2. Slamon DJ, Stroyakovskiy D, Yardley DA, et al: Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2– early breast cancer: Primary results from the phase III NATALEE trial. 2023 ASCO Annual Meeting. Abstract LBA500. Presented June 4, 2023.

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