A recent retrospective study conducted at the King Hussein Cancer Center has affirmed the effectiveness and safety of ribociclib in combination with endocrine therapy for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) in a real-world setting. The findings, which included 356 patients, highlight the consistency of clinical outcomes compared to those observed in controlled clinical trials.
The study, which retrospectively analyzed data from patients treated between June 2017 and May 2020, aimed to assess the clinical benefit and safety profile of ribociclib in a patient population that is often underrepresented in clinical trials. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), adverse events, dose reduction, and discontinuation rates.
Key Findings on Efficacy
The median age of patients was 52 years, with 46.9% being premenopausal. The majority of patients (63.8%) received CDK4/6 inhibitors as first-line therapy. The median overall survival (OS) for the entire group was 40.6 months (95% CI, 33.5–48.6), while the median progression-free survival (PFS) was 27.3 months (95% CI, 21.3–31.7). Patients who received CDK4/6 inhibitors as first-line therapy had a better PFS (32.1 months; 95% CI 27.7–42.1) compared to those who received it as a second line (25.7 months, 95% CI 15.3–33.7) or beyond (11.7 months, 95% CI 9.6–16.3), p<0.0001.
Safety and Tolerability
Dose reduction was required in 101 patients (28.4%), primarily due to neutropenia (21.3%) and abnormal liver enzyme levels (5.9%). Treatment was discontinued due to toxicities in 7.9% of patients, with cardiac and liver toxicities being the most common reasons. Importantly, no deaths occurred due to toxicity.
Impact of Treatment Line and Metastasis Site
The study also found that PFS was better for patients treated with CDK4/6 inhibitors for non-visceral metastasis (38.6 months, 95% CI 29.8-NR) than for those with visceral metastasis (19.4 months, 95% CI 16.6–26.1), p<0.0001. In multivariate analysis, the line of treatment, endocrine companion, site of metastasis, and timing of metastasis had a significant impact on OS.
Comparison with Clinical Trials
The real-world outcomes observed in this study align with those reported in the MONALEESA trial program, which assessed ribociclib in multiple Phase III clinical trials. The MONALEESA trials demonstrated consistently superior clinical benefit with ribociclib + ET compared to ET alone, including significant improvement in overall survival (OS) in both premenopausal and postmenopausal women.
Implications for Clinical Practice
These findings reinforce the role of ribociclib as an effective treatment option for HR+/HER2- MBC in routine clinical practice. The study's authors emphasize the importance of real-world data in confirming the efficacy and safety of new treatment regimens in diverse patient populations, including those often excluded from clinical trials. The results suggest that even in lower-resourced settings, similar treatment outcomes can be achieved with CDK4/6 inhibitors when integrated into clinical practice.
Study Limitations
The authors acknowledge several limitations, including the retrospective nature of the study, its single-center design, and potential under-reporting of adverse events. Additionally, the study did not include a control group of patients who received endocrine therapy alone.
Despite these limitations, the study provides valuable insights into the real-world effectiveness of ribociclib in treating HR+/HER2- MBC, supporting its use as a standard treatment option in this patient population.
