In a recent analysis conducted at a single center, ribociclib (Kisqali; Novartis) was found to be associated with significantly higher rates of early treatment modifications compared to palbociclib (Ibrance; Pfizer) in patients diagnosed with hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer. The study highlighted that these modifications, which included dose reductions and delays, predominantly occurred within the first six cycles of therapy.
Understanding the Current Landscape of HR+/HER2– Breast Cancer Treatment
HR+/HER2– breast cancer is the most prevalent subtype of breast cancer and has seen a transformative shift in treatment approaches with the introduction of CDK4/6 inhibitors. These medications, when combined with endocrine therapy, have consistently shown to enhance progression-free survival (PFS) and, in some instances, overall survival (OS) across various randomized clinical trials. Ribociclib and palbociclib were among the first CDK4/6 inhibitors to receive approval for treatment in this context and are now commonly utilized in both initial and subsequent therapy lines.
While the pivotal trials have confirmed their efficacy, understanding their real-world performance remains critical. A recent retrospective analysis aimed to assess treatment modifications, discontinuations, and survival outcomes associated with ribociclib and palbociclib in routine clinical practice. The study reviewed cases of patients treated between June 1, 2014, and June 1, 2024, who had metastatic or unresectable advanced HR+/HER2– breast cancer and were receiving endocrine therapy alongside either ribociclib or palbociclib.
Key Findings on Treatment Modifications and Outcomes
The primary endpoints of the study included dose reductions, dose delays, and treatment discontinuations during the initial six cycles of therapy, with PFS evaluated as a secondary endpoint. Statistical comparisons were conducted using chi-squared testing, while PFS was analyzed through Kaplan-Meier survival methods.
Among the 84 patients analyzed, 43 were treated with palbociclib and 41 with ribociclib. Notably, dose reductions were observed in **34.8%** of patients on palbociclib, compared to **58.5%** of those treated with ribociclib, marking a statistically significant difference. The majority of these reductions occurred early in the treatment course, with two-thirds of palbociclib dose reductions and over **80%** of ribociclib reductions taking place within the first six cycles.
Treatment delays mirrored these findings, with delays affecting **39.5%** of patients receiving palbociclib and **58.5%** for those on ribociclib, again showing a significant statistical difference. The early cycles of therapy thus appear critical for monitoring and managing patient responses.
Neutropenia emerged as the primary reason for dose modifications across both treatment groups. This aligns with established safety profiles of CDK4/6 inhibitors and emphasizes the necessity for routine blood count monitoring, particularly during initial cycles. Additionally, hepatotoxicity was reported among ribociclib patients, consistent with adverse events noted in clinical trials.
Despite the higher rates of dose modifications associated with ribociclib, treatment discontinuation rates prior to completing six cycles were similar between the two groups. Discontinuation occurred in **24.4%** of patients on palbociclib and **19.5%** on ribociclib, with no significant difference identified.
Moreover, the analysis revealed no statistically significant difference in PFS between the two agents among patients receiving CDK4/6 inhibitors combined with an aromatase inhibitor. Although there were numerical trends favoring ribociclib, the study lacked sufficient power to detect minor differences in survival outcomes, suggesting that larger datasets or multi-center studies may be necessary for further exploration.
The insights from this retrospective analysis underscore the importance of early toxicity management and individualized dose adjustments in the treatment of HR+/HER2– advanced breast cancer. While ribociclib showed higher rates of dose reductions and delays, these adjustments did not adversely impact treatment continuation or PFS outcomes. As the use of CDK4/6 inhibitors expands, a proactive approach to monitoring and managing side effects will be crucial for optimizing patient care.
