CDK4/6 inhibitors in metastatic breast cancer, a comparison of toxicity and efficacy across agents in a real-world dataset

Abstract

Introduction CDK4/6 inhibitors (ribociclib, palbociclib and abemaciclib) are 1st line therapy in metastatic breast cancer (MBC). No comparative data exists between agents regarding toxicity or efficacy. Methods A retrospective study was performed at our tertiary referral centre evaluating patients on a CDK4/6 inhibitor for MBC between July 2017 and December 2021. Toxicity was evaluated along with variability in full blood counts and liver function over the first 12 weeks of therapy. Results Two hundred and seventeen patients were treated (palbociclib 59%, abemaciclib 25% and ribociclib 16%). 86% received the agent as 1st line therapy. Most patients were white women with a median age of 61 years (32–95) and ECOG 0/1. Twelve patients were switched to an alternative CDK4/6 inhibitor due to toxicity and two did not tolerate this. Toxicity profiles of agents were consistent with published trials. However, there was greater overlap in hepatitis, diarrhoea and bone marrow suppression. Blood results indicated a minimum of four weeks treatment before development of neutropenia. Forty percent of patients went onto have subsequent lines of therapy. The progression-free survival per agent was palbociclib 27.9 months (95% CI 23–32.5), ribociclib 29 months (95% CI 21.5–37.0) and abemaciclib 20.6 months (95% CI 15.0–26.0). The overall survival was palbociclib 38.0 months (95% CI 33.5–42.5), ribociclib 33.9 months (95% CI 26.7–41.1) and abemaciclib 27.3 months (95% CI 22.5–32.1). Conclusions Toxicity across CDK4/6 inhibitors overlaps. The optimal sequence of therapies post CDK4/6 inhibitors remains unknown but rechallenge with an alternative agent is possible.

Prognostic and Predictive Significance of HER2-low Expression in Metastatic Hormone Receptor Positive Breast Cancer Patients Receiving CDK4-6 Inhibitor Therapy

“…There was no difference between the median PFS of our patients who received ribociclib or palbociclib treatment. In a study in which real-life data were analyzed, the PFS times were similar for palbociclib and ribociclib (28 and 29 months, respectively) [18]. In our study, mPFS was significantly different between patients who received cytotoxic chemotherapy before CDK4/6 in the metastatic period and those who received CDK4/6i treatment as first-line treatment [19].…”

“…(95% CI,[14][15][16][17][18][19][20][21][22][23][24] months in the fulvestrant+ribociclib group (p=0.001) (Figure-3A).…”

Acute-on-Chronic Liver Failure Incited by Cyclin-Dependent Kinase Inhibitor Therapy for Breast Cancer Effectively Treated With Liver Transplantation

“… 1 Review of CDK4/6 inhibitor toxicity in a recent retrospective study suggests the possibility of safely rechallenging with an alternative CDK4/6 inhibitor, which may support the hypothesis that CDK4/6 inhibitors mediate idiosyncratic liver injuries. 4 …”

Effectiveness of cyclin-dependent kinase 4 and 6 inhibitors for the treatment of hormonesensitive HER2-negative metastatic breast cancer in first-line therapy: A systematic literature review

“…Рибоциклиб + ГТ (n = 54, в том числе 34 в комбинации с ИА) Абемациклиб + ГТ (n = 56, в том числе 29 в комбинации с ИА) Palbociclib + HT (n = 96, including 53 in combination with AI) Ribociclib + HT (n = 54, including 34 in combination with AI) Abemaciclib + HT (n = 56, including 29 in combination with AI) Палбоциклиб + ГТ (n = 79, в том числе 37 -в составе 1-й линии, 34 -в комбинации с ИА) Рибоциклиб + ГТ (n = 42, в том числе 33 -в составе 1-й линии, 31 -в комбинации с ИА) Абемациклиб + ГТ (n = 21, в том числе 9 -в составе 1-й линии, 9 -в комбинации с ИА) Palbociclib + HT (n = 79, including 37 as first-line therapy, 34 in combination with AI) Ribociclib + HT (n = 42 including 33 as first-line therapy, 31 in combination with AI) Abemaciclib + HT (n = 21, including 9 as first-line therapy, 9 in combination with AI) Палбоциклиб + ГТ (n = 33, в том числе 6 -в составе 1-й линии, 8 -в комбинации с ИА) Рибоциклиб + ГТ (n = 28, в том числе 19 -в составе 1-й линии, 25 -в комбинации с ИА) Palbociclib + HT (n = 33, including 6 as first-line therapy, 8 in combination with AI) Ribociclib + HT (n = 28, including 19 as first-line therapy, 25 in combination with AI)No Таблица 1. Общая характеристика отобранных исследований[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] …”

“…General characteristics of the studies included[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] …”