More Dose Adjustments, Similar Outcomes: Ribociclib vs Palbociclib in Practice

In a real-world, single-center analysis, ribociclib (Kisqali; Novartis) was associated with significantly higher rates of early treatment modification—specifically dose reductions and dose delays—compared with palbociclib (Ibrance; Pfizer) in patients with hormone receptor–positive, HER2-negative (HR+/HER2–) breast cancer. These outcomes were present within the first 6 cycles of therapy.

Remain a Backbone of Care in HR+/HER2– Breast Cancer

HR+/HER2– breast cancer represents the most common subtype of breast cancer, and the introduction of CDK4/6 inhibitors has fundamentally reshaped treatment paradigms for patients with advanced or metastatic disease. When combined with endocrine therapy, CDK4/6 inhibitors have consistently demonstrated improvements in progression-free survival (PFS) and, in some cases, overall survival (OS), across multiple randomized trials.¹

Palbociclib and ribociclib were among the first CDK4/6 inhibitors approved in this setting and are now widely used in both first- and later-line therapy. While pivotal trials established their efficacy, real-world experience continues to clarify how these agents are tolerated outside of controlled clinical trial settings. A recent single-center retrospective analysis sought to evaluate treatment modifications, discontinuations, and survival outcomes associated with palbociclib and ribociclib in routine clinical practice.¹

Ribociclib Demonstrated Overall Survival Benefit in Pivotal Trials

Ribociclib has distinguished itself among CDK4/6 inhibitors through consistent overall survival benefits reported across the MONALEESA clinical trial program. In MONALEESA-2 (NCT01958021),² ribociclib combined with letrozole significantly improved both PFS and OS compared with endocrine therapy alone in the first-line setting.³

These survival gains have positioned ribociclib as a preferred option in many treatment guidelines. However, ribociclib is also associated with a distinct toxicity profile, including hepatotoxicity and QT interval prolongation, in addition to class-wide hematologic adverse events such as neutropenia.

Palbociclib Improved Progression-Free Survival Without Demonstrating OS Benefit

Palbociclib was the first CDK4/6 inhibitor to gain FDA approval based on the PALOMA trial program. In PALOMA-2 (NCT05498428),⁴ palbociclib plus letrozole significantly improved PFS compared with letrozole alone in the first-line setting for HR+/HER2– advanced breast cancer.

Despite these gains, palbociclib has not demonstrated a statistically significant OS benefit in randomized trials. Nonetheless, it remains widely used due to clinician familiarity, predictable toxicity management, and established efficacy in delaying disease progression.

Real-World Study Examined Treatment Modifications

To better understand how palbociclib and ribociclib perform outside of clinical trials, investigators conducted a single-center retrospective review of patients treated between June 1, 2014, and June 1, 2024. Eligible patients had metastatic or unresectable advanced HR+/HER2– breast cancer and were initiated on endocrine therapy in combination with either palbociclib or ribociclib.⁵

The primary endpoints included dose reductions, dose delays, and treatment cessation within the first 6 cycles of therapy. PFS was evaluated as a secondary endpoint. Statistical comparisons were performed using chi-squared testing, while PFS was assessed via Kaplan-Meier survival analysis.⁵

Ribociclib Required Significantly More Dose Reductions Than Palbociclib

Among the 84 patients included in the analysis, 43 received palbociclib and 41 received ribociclib. Dose reductions occurred in 34.8% of patients treated with palbociclib compared with 58.5% of those treated with ribociclib—a statistically significant difference.⁵

Most dose reductions occurred early in treatment. Two-thirds of palbociclib dose reductions and more than 80% of ribociclib dose reductions took place within the first 6 cycles. A subset of patients in both groups required multiple dose reductions during this early treatment period.⁵

Ribociclib Was Associated With Higher Rates of Early Treatment Delays

Treatment delays followed a similar pattern. Delays occurred in 39.5% of patients receiving palbociclib and 58.5% of patients receiving ribociclib, with the difference reaching statistical significance.⁵

The vast majority of delays in both treatment groups occurred within the first 6 cycles of therapy, underscoring the importance of close monitoring early in treatment initiation.⁵

Neutropenia Drove Most Dose Modifications Across Both Agents

Neutropenia was the most commonly cited reason for both dose reductions and dose delays in patients treated with palbociclib and ribociclib. This finding aligns with the established safety profiles of CDK4/6 inhibitors and reinforces the need for routine blood count monitoring, particularly during the initial cycles of therapy.⁵

Hepatotoxicity was also noted among patients receiving ribociclib, consistent with known adverse event patterns reported in clinical trials.⁵

Treatment Discontinuation Rates Were Similar Between Palbociclib and Ribociclib

Despite higher rates of dose modification with ribociclib, treatment discontinuation prior to completion of six cycles was comparable between groups. Discontinuation occurred in 24.4% of patients treated with palbociclib and 19.5% of those treated with ribociclib, with no statistically significant difference observed.⁵

These findings suggest that while ribociclib may require more frequent dose adjustments, patients are generally able to remain on therapy at adjusted doses.⁵

PFS Did Not Differ Significantly Between Agents

Among patients receiving CDK4/6 inhibitors in combination with an aromatase inhibitor, no statistically significant difference in PFS was observed between palbociclib and ribociclib. Although numerical trends favored ribociclib, the study was not powered to detect small differences in survival outcomes.⁵

Investigators noted that a larger dataset or multi-center analysis may be necessary to further explore potential survival differences in real-world settings.⁵

Real-World Data Reinforce the Importance of Early Toxicity Management

This retrospective analysis highlights meaningful differences in treatment modification patterns between palbociclib and ribociclib while reaffirming the central role of CDK4/6 inhibitors in HR+/HER2– advanced breast cancer. Ribociclib was associated with higher rates of dose reductions and delays, particularly early in therapy, but these adjustments did not translate into higher discontinuation rates or inferior PFS.

As CDK4/6 inhibitors continue to be used earlier and for longer durations, proactive toxicity monitoring and individualized dose management remain essential to optimizing outcomes in real-world clinical practice.

REFERENCES

1. Gerlach A. How next-generation CDK inhibitors are redefining post–CDK4/6 therapy in HR+/HER2– metastatic breast cancer. Pharmacy Times. December 11, 2025. Accessed December 19, 2025. https://www.pharmacytimes.com/view/how-next-generation-cdk-inhibitors-are-redefining-post-cdk4-6-therapy-in-hr-her2-metastatic-breast-cancer

2. Study of efficacy and safety of LEE011 in postmenopausal women with advanced breast cancer (MONALEESA-2). ClinicalTrials.gov. Updated March 7, 2025. Accessed December 19, 2025. https://clinicaltrials.gov/study/NCT01958021

3. Gerlach A. MONALEESA data reveal robust long-term disease control with ribociclib. Pharmacy Times. December 9, 2025. Accessed December 19, 2025. https://www.pharmacytimes.com/view/monaleesa-data-reveal-robust-long-term-disease-control-with-ribociclib

4. A study of amivantamab in participants with advanced or metastatic solid tumors including epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (PALOMA-2). Clinicaltrials.gov. Updated December 19, 2025. Accessed December, 19, 2025. https://clinicaltrials.gov/study/NCT05498428

5. Steele C, Shaw J, O’Connor D, et al. A retrospective study to assess real world rates of dose modification, therapy discontinuation and treatment outcomes in patients receiving the oral CDK4/6 inhibitors Ribociclib and Palbociclib. Presented at: SABCS 2025. December 9-12, 2025. Abstract PS1-08-13