Cancer Res Treat.  2023 Oct;55(4):1198-1209. 10.4143/crt.2022.1543.

Efficacy of Limited Dose Modifications for Palbociclib-Related Grade 3 Neutropenia in Hormone Receptor–Positive Metastatic Breast Cancer

• Kim SG
• Kim MH
• Park S
• Kim GM
• Kim JH
• Kim JY
• Park HS
• Park S
• Park BW
• Kim SI
• Ji JH
• Jeong J
• Shin K
• Lee J
• Kim HD
• Jung KH
• Sohn J

• KMID: 2547794
• DOI: http://doi.org/10.4143/crt.2022.1543

Abstract

Purpose
Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)–positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia.
Materials and Methods
Patients with HR-positive, human epidermal growth factor receptor 2–negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups.
Results
During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality.
Conclusion
Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.

Keyword

Palbociclib; Limited dose modification; Afebrile neutropenia; Metastatic breast cancer; Progression-free survival

Figure

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  Fig. 1 Consort diagram and patient grouping according to dose modification scheme.

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  Fig. 2 Cumulative incidence of palbociclib dose reduction in groups 1 and 2 (n=302). Kaplan-Meier curves showing cumulative dose reduction rates over time among group 1 (A) and group 2 (B). Number at risk is shown at the bottom of the graph, with number of censored patients in parentheses.

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  Fig. 3 Survival outcomes after dose modification for afebrile grade 3 neutropenia. Progression-free survival (A) and overall survival (B) of group 1 and group 2 patients (n=302). Number at risk is shown at the bottom of the graph, with number of censored patients in parentheses.

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  Fig. 4 Forest plot of the HR for progression-free survival by subgroup analysis comparing group 1 with group 2 (n=302). CI, confidence interval; HR, hazard ratio.

Reference

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