Analysis of the selection of CDK4/6 inhibitors based on experience using palbociclib

Kikuchi, Masatoshi; Tanaka, Yôko; Yokota, Mitsuo; Nishimiya, Hiroshi; Katoh, Hiroshi; Sengoku, Norihiko; Kosaka, Yoshimasa

doi:10.3892/br.2019.1248

Cited by 7 publications

(7 citation statements)

References 9 publications

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“…In Japan, the real-world efficacy of palbociclib was analyzed in 4 retrospective studies (Table 2) [55][56][57][58]. Whereas the sample sizes of Japanese real-world studies were small, the efficacy and safety results seem to be consistent with global real-world data.…”

Section: Real-world Evidence Regarding Treatment With Palbociclibmentioning

confidence: 98%

Palbociclib as an early-line treatment for Japanese patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: a review of clinical trial and real-world data

et al. 2021

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Breast cancer is the most common type of cancer among women worldwide and in Japan. The majority of breast cancers are hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2‒), and endocrine therapy is an effective therapy for this type of breast cancer. However, recent substantial advances have been made in the management of HR+/HER2‒ advanced breast cancer (ABC) with the advent of targeted therapies, such as cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, resulting in significant improvements in survival outcomes versus endocrine therapy alone. To evaluate the optimal use of palbociclib, a CDK4/6 inhibitor, in HR+/HER2– ABC, this review summarizes clinical trial and real-world data for palbociclib. In addition, current biomarker studies in palbociclib clinical research are reviewed. In Japanese patients, palbociclib was shown to be effective with a manageable safety profile, although differences were observed in the frequency of adverse event and dosing parameters. Current evidence supporting palbociclib as a first-line treatment strategy for patients with HR+/HER2‒ ABC in Asia, and specifically japan, is also discussed.

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Section: Real-world Evidence Regarding Treatment With Palbociclibmentioning

confidence: 98%

Palbociclib as an early-line treatment for Japanese patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: a review of clinical trial and real-world data

et al. 2021

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“…In addition, most patients have different backgrounds and characteristics, such as age, line of therapy, and comorbidities, from the subjects in these clinical studies. Given that previous Japanese studies have only investigated treatment with palbociclib in clinical trial settings or small populations, 11 - 13 it is essential to evaluate the effectiveness of palbociclib in a larger, real-world setting and investigate the predictive factors for its efficacy using lactate dehydrogenase (LDH) 14 and neutrophil-to-lymphocyte ratio (NLR) 15 as clinical markers. In this study, we investigated the effectiveness, predictive factors, and safety of palbociclib for the treatment of patients with ABC in routine clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Real-World Outcomes of Treating Advanced Breast Cancer Patients With Palbociclib: A Multicenter Retrospective Cohort Study in Japan—The KBCOG-14 Study

Odan

Kikawa

Matsumoto

et al. 2020

Breast Cancer�(Auckl)

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Background: Clinical studies have shown that palbociclib improves progression-free survival in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) patients with advanced breast cancer (ABC). However, there are insufficient data on its use in a real-world setting in Japan. The aim of this study was to investigate the effectiveness, predictive factors, and safety of palbociclib among Japanese patients in routine clinical practice. Methods: Between December 1, 2017, and April 30, 2019, we recruited patients from 9 hospitals and retrospectively evaluated the data on HR+/HER2− patients with ABC who received palbociclib for at least 1 week. The correlation between time-to-treatment discontinuation (TTD) and clinical background was investigated via univariate and multivariate analyses using Cox hazards models. Results: A total of 177 women were available for analysis. Of these patients, 58 (33%) patients were treated with palbociclib with an aromatase inhibitor and 117 (66%) patients were treated with palbociclib and a selective estrogen receptor degrader. Approximately three-fourths of the patients (n = 130, 73%) received palbociclib as third- or later-line therapy. One-third of the patients had 3 or more metastatic sites (n = 59, 33%), and one-third of the patients had liver metastasis (n = 59, 33%). The median follow-up duration at the time of data cutoff was 8.9 months, the median TTD was 6.3 months, and the median overall survival was not reached. Liver metastasis (hazard ratio [HR]: 1.54 [95% confidence interval {CI}: 1.03-2.27]), high serum lactate dehydrogenase (LDH) level (>300 U/L) (HR: 2.58 [95% CI: 1.49-4.26]), and high neutrophil-to-lymphocyte ratio (NLR) (⩾3.0) (HR: 1.76 [95% CI: 1.13-2.69]) were significantly associated with shorter TTD. The most common hematologic adverse event was neutropenia, which occurred in 93% of the patients. Conclusion: Based on the results of the pivotal phase 3 trials, the median TTD recorded in this study was shorter than expected. Our results suggest that liver metastasis, serum LDH level, and NLR may be predictive factors for HR+/HER2− ABC treatment outcomes.

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“…Third, a previous study reported that a baseline neutrophil count of <3000/µL might be a marker for selecting CDK4/6 inhibitors. 13) However, we could not determine which was a better marker, WBC or neutrophil count, because of a lack of neutrophil count. Fourth, the observation period was 60 d. It has been previously reported that neutropenia associated with palbociclib usually occurred within the first 28 d and that associated with abemaciclib within 56 d. The median time to the occurrence of diarrhea due to abemaciclib was 6 d. 3) Since most of the adverse effects developed within 60 d, it is a reasonable observation period.…”

Section: Discussionmentioning

confidence: 96%

“…8) Kikuchi et al reported that 37% of Japanese patients required dose reduction in their case series. 13) On the other hand, Toi et al reported that race was not a significant covariate of pharmacokinetic parameters and concentration of abemaciclib. 14) These previous findings are consistent with our results and suggest that the frequent SAEs in the palbociclib group of this study might be attributable to ethnic differences.…”

Section: Discussionmentioning

confidence: 98%

The Cyclin-Dependent Kinase 4/6 Inhibitor Abemaciclib Is Tolerated Better than Palbociclib by Advanced Breast Cancer Patients with High Serum Albumin Levels

Nakatsukasa

Takahashi

et al. 2022

Biological & Pharmaceutical Bulletin

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The cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib, have been approved in Japan. However, the selection criteria for these drugs have not been established. Hence, we aimed to identify the risk factors for CDK4/6 inhibitor-induced intolerable adverse events requiring dose reduction or therapy cessation and to establish useful markers for choosing the appropriate CDK4/6 inhibitor, based on the incidence of the intolerable adverse events. This retrospective cohort analysis included patients with advanced breast cancer who received 125 mg/d palbociclib or 300 mg/d abemaciclib. We defined significant adverse events (SAEs) as side effects requiring dose reduction or therapy cessation. Thirty-six percent of the patients who received palbociclib (9/25) and 27.3% of those who received abemaciclib (9/33) experienced SAEs. In palbociclib and abemaciclib groups, baseline white blood cell (WBC) counts and serum albumin (ALB) levels, respectively, were significantly lower in patients who experienced SAEs than in those who did not (palbociclib: p 0.007; abemaciclib: p 0.004). According to the receiver operating characteristic curve analysis, the optimal cutoff values for baseline WBC count and ALB level were 5700/µL and 4.0 g/dL, respectively. Among patients with ALB levels >4.0 g/dL, the incidence of abemaciclib-induced SAEs was significantly lower than that of the palbociclib-induced SAEs (1/17 (5.9%) vs. 6/14 (42.9%), odds ratio: 11.0, 95% confidence interval: 1.07-583, p 0.0281). Thus, a baseline WBC count ≤5700/µL and ALB level ≤4.0 g/dL may be risk factors for palbociclib and abemaciclib-induced SAEs, respectively. Also, high ALB levels can serve as a useful marker for choosing abemaciclib.

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Analysis of the selection of CDK4/6 inhibitors based on experience using palbociclib

Cited by 7 publications

References 9 publications

Palbociclib as an early-line treatment for Japanese patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: a review of clinical trial and real-world data

Palbociclib as an early-line treatment for Japanese patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: a review of clinical trial and real-world data

Real-World Outcomes of Treating Advanced Breast Cancer Patients With Palbociclib: A Multicenter Retrospective Cohort Study in Japan—The KBCOG-14 Study

The Cyclin-Dependent Kinase 4/6 Inhibitor Abemaciclib Is Tolerated Better than Palbociclib by Advanced Breast Cancer Patients with High Serum Albumin Levels

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