Dose modifications of ribociclib and endocrine therapy for treatment of ER+ HER2− metastatic breast cancer

Kristensen, Kristoffer Bøss; Thomsen, Ida Marie Nedergaard; Berg, Tobias; Kodahl, Annette Raskov; Jensen, Anders Bonde

doi:10.1007/s10549-021-06215-6

Cited by 11 publications

(18 citation statements)

References 33 publications

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“…6 Side effects of palbociclib and ribociclib (particularly hematologic) can be overcome by dose reduction and do not affect disease outcome in the metastatic setting. 24,25 It is hypothesized that those patients have a higher pharmacodynamic impact of the drug, meaning that a lower dosage results in comparable efficacy and side effects. 26 Conversely, less frequent or severe side effects of CDK4/6is given at a full dose may suggest a lower pharmacodynamic impact and, therefore, limited efficacy of these drugs.…”

Section: Discussionmentioning

confidence: 99%

Impact of BMI in Patients With Early Hormone Receptor–Positive Breast Cancer Receiving Endocrine Therapy With or Without Palbociclib in the PALLAS Trial

Pfeiler,

Hlauschek,

Mayer

et al. 2023

JCO

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PURPOSE BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib. METHODS Patients were categorized at baseline according to WHO BMI categories. Neutropenia rates were assessed with univariable and multivariable logistic regression. Time to early discontinuation of palbociclib was analyzed with Fine and Gray competing risk models. Unstratified Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). 95% CIs were derived. RESULTS Of 5,698 patients included in this analysis, 68 (1.2%) were underweight, 2,082 (36.5%) normal weight, 1,818 (31.9%) overweight, and 1,730 (30.4%) obese at baseline. In the palbociclib arm, higher BMI was associated with a significant decrease in neutropenia (unadjusted odds ratio for 1-unit change, 0.93; 95% CI, 0.91 to 0.94; adjusted for age, race ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group at baseline, 0.93; 95% CI, 0.92 to 0.95). This translated into a significant decrease in treatment discontinuation rate with higher BMI (adjusted hazard ratio [HR] for 10-unit change, 0.75; 95% CI, 0.67 to 0.83). There was no significant improvement in iDFS with the addition of palbociclib to ET in any weight category (normal weight HR, 0.84; 95% CI, 0.63 to 1.12; overweight HR, 1.10; 95% CI, 0.82 to 1.49; and obese HR, 0.95; 95% CI, 0.69 to 1.30) in this analysis early in follow-up (31 months). CONCLUSION This preplanned analysis of the PALLAS trial demonstrates a significant impact of BMI on side effects, dose reductions, early treatment discontinuation, and relative dose intensity. Additional long-term follow-up will further evaluate whether BMI ultimately affects outcome.

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Section: Discussionmentioning

confidence: 99%

Impact of BMI in Patients With Early Hormone Receptor–Positive Breast Cancer Receiving Endocrine Therapy With or Without Palbociclib in the PALLAS Trial

Pfeiler,

Hlauschek,

Mayer

et al. 2023

JCO

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“…(75%). 7,10 This can be explained as first approvals of ribociclib were in first-line treatment setting in European Medicines Agency (EMA). 3…”

Section: Discussionmentioning

confidence: 99%

Real-world effectiveness of ribociclib in metastatic breast cancer patients: Does dose affect survival?

Fernández-Cuerva

Chinchilla-Alarcón

Alcaraz-Sánchez

2022

J Oncol Pharm Pract

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Introduction: Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. The purpose of this study was to assess real-world security profile and management of adverse events (AEs) presented with ribociclib for the treatment of HR + /HER2− metastatic breast cancer (MBC). Our secondary objective was to provide real-world effectiveness of this treatment (measured with progression-free survival (PFS)) and to confirm the hypothesis that dose reductions are not related with disease progression. Material and methods: Observational retrospective study evaluating all females with MBC treated with ribociclib. Study period: January 2017 to September 2019. Follow-up was done until November 2021. Response was assessed through the PFS according to RECIST1.1 and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) was used to classify AEs. Results: The most common AE was any grade neutropenia, documented in 37 of 53 patients (69.8%) during the course of treatment. By the end of the follow-up period, overall median PFS with ribociclib therapy was 27.3 months (95% confidence interval (CI) 20.8–71.8 months). In total, 50 patients (94.4%) initiated ribociclib at 600 mg dose, 28 patients (58%) required dose reductions. PFS of patients receiving ribociclib as first-line treatment was 28 (95% CI 15–41 months). Conclusions: Our results from patients treated in real-world clinical settings indicate that ribociclib is safe and their AEs are manageable with active monitoring, temporal suspension of treatment and dose reduction. Furthermore, our results indicate that dose reduction of ribociclib is not associated with a loss of efficacy.

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“…However, approximately 81% of patients reported diarrhea (grade 3/4 in 9.5%) in MONARCH 3; grade 1 and 2 AEs can adversely affect quality of life . Despite the high incidence of neutropenia with CDK4/6i, febrile neutropenia is rare, and dose modifications for grade 3 to 4 neutropenia have not negatively affected PFS . Other uncommon but severe adverse effects include interstitial lung disease/pneumonitis (1.6%) and venous thromboembolic events (0.6%-5%).…”

Section: Toxic Effectsmentioning

confidence: 99%

Cyclin-Dependent Kinase 4/6 Inhibitors for Treatment of Hormone Receptor–Positive, ERBB2-Negative Breast Cancer

et al. 2023

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ImportanceCombination therapy with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i: palbociclib, ribociclib, abemaciclib) and endocrine therapy (ET) has been a major advance for the treatment of hormone receptor–positive (HR+), ERBB2 (formerly HER2)–negative (ERBB2−) advanced or metastatic breast cancer.ObservationsRandomized phase 3 studies demonstrated that the addition of CDK4/6i reduced the hazard risk of disease progression by approximately half compared with hormonal monotherapy (an aromatase inhibitor, tamoxifen, or fulvestrant) in the first-line (1L) and/or second-line (2L) setting. Hence, the US Food and Drug Administration and European Medicines Agency approved 3 CDK4/6i, in both 1L and 2L settings. However, differences among the CDK4/6i regarding mechanisms of action, adverse effect profiles, and overall survival (OS) are emerging. Both abemaciclib and ribociclib have demonstrated efficacy in high-risk HR+ early breast cancer. While ET with or without CDK4/6i is accepted as standard treatment for persons with advanced HR+ ERBB2− metastatic breast cancer, several key issues remain. First, why are there discordances in OS in the metastatic setting and efficacy differences in the adjuvant setting? Additionally, apart from HR status, there are few biomarkers predictive of response to CDK4/6i plus ET, and these are not used routinely. Despite the clear OS advantage noted in the 1L and 2L metastatic setting with some CDK4/6i, a subset of patients with highly endocrine-sensitive disease do well with ET alone. Therefore, an unanswered question is whether some patients can postpone CDK4/6i until the 2L setting, particularly if financial toxicity is a concern. Finally, given the lack of endocrine responsiveness following progression on some CDK4/6i, strategies to optimally sequence treatment are needed.Conclusions and RelevanceFuture research should focus on defining the role of each CDK4/6i in HR+ breast cancer and developing a biomarker-directed integration of these agents.

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Dose modifications of ribociclib and endocrine therapy for treatment of ER+ HER2− metastatic breast cancer

Cited by 11 publications

References 33 publications

Impact of BMI in Patients With Early Hormone Receptor–Positive Breast Cancer Receiving Endocrine Therapy With or Without Palbociclib in the PALLAS Trial

Impact of BMI in Patients With Early Hormone Receptor–Positive Breast Cancer Receiving Endocrine Therapy With or Without Palbociclib in the PALLAS Trial

Real-world effectiveness of ribociclib in metastatic breast cancer patients: Does dose affect survival?

Cyclin-Dependent Kinase 4/6 Inhibitors for Treatment of Hormone Receptor–Positive, ERBB2-Negative Breast Cancer

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