Dose optimisation of carboplatin in the TCbHP neoadjuvant regimen for HER2-Positive breast cancer: a real-world dose–response analysis using restricted cubic splines
Abstract
BackgroundThe docetaxel–carboplatin–trastuzumab–pertuzumab (TCbHP) regimen is widely used as a standard neoadjuvant strategy for HER2-positive breast cancer and provides substantial pathologic complete response (pCR) benefits. However, evidence on the optimal balance between treatment efficacy and toxicity remains limited.ObjectivesThis study aimed to evaluate the dose–response relationship between carboplatin exposure and pCR and to explore its association with treatment-related adverse events.MethodsIn this retrospective study, clinical data were collected from patients with HER2-positive breast cancer who received the TCbHP neoadjuvant regimen followed by surgery at two tertiary hospitals between January 2019 and December 2023. Restricted cubic spline (RCS) models and Firth’s bias-reduced penalized-likelihood logistic regression analyses were applied to assess the association and dose–response relationship between actual carboplatin exposure (dAUC) and pCR after adjustment for relevant confounders.ResultsAmong 153 eligible patients, 107 (69.9%) achieved pCR. Patients with pCR had significantly higher carboplatin exposure compared with those without pCR. RCS analysis demonstrated a significant linear dose–response relationship between carboplatin dAUC and pCR probability (overall trend p = 0.050; non-linearity p = 0.114), with an exploratory exposure threshold of 5.49 mg min/mL. Multivariable logistic regression confirmed that higher carboplatin exposure, as measured by dAUC, was independently associated with reduced odds of achieving non-pCR. However, excessively high carboplatin exposure was significantly associated with an elevated risk of thrombocytopenia, while patients who experienced liver injury exhibited lower carboplatin exposure.ConclusionCarboplatin exposure showed a linear association with pCR in patients receiving the TCbHP neoadjuvant regimen. Low exploratory exposure (5.49 mg min/mL) may compromise treatment efficacy, while excessively high exposure may increase hematologic toxicity. These findings provide real-world evidence to support individualized carboplatin dosing strategies aimed at optimizing the efficacy–toxicity balance.
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BibTeX
@article{lu2026dose,
title = {{Dose optimisation of carboplatin in the TCbHP neoadjuvant regimen for HER2-Positive breast cancer: a real-world dose–response analysis using restricted cubic splines}},
author = {Yi Lu and Binbin Cui and Jun Shen and Linbo Wang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1942819},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1942819},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dose optimisation of carboplatin in the TCbHP neoadjuvant regimen for HER2-Positive breast cancer: a real-world dose–response analysis using restricted cubic splines
AU - Yi Lu
AU - Binbin Cui
AU - Jun Shen
AU - Linbo Wang
PY - 2026
DA - 2026/11/09
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1942819
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1942819
AB - BackgroundThe docetaxel–carboplatin–trastuzumab–pertuzumab (TCbHP) regimen is widely used as a standard neoadjuvant strategy for HER2-positive breast cancer and provides substantial pathologic complete response (pCR) benefits. However, evidence on the optimal balance between treatment efficacy and toxicity remains limited.ObjectivesThis study aimed to evaluate the dose–response relationship between carboplatin exposure and pCR and to explore its association with treatment-related adverse events.MethodsIn this retrospective study, clinical data were collected from patients with HER2-positive breast cancer who received the TCbHP neoadjuvant regimen followed by surgery at two tertiary hospitals between January 2019 and December 2023. Restricted cubic spline (RCS) models and Firth’s bias-reduced penalized-likelihood logistic regression analyses were applied to assess the association and dose–response relationship between actual carboplatin exposure (dAUC) and pCR after adjustment for relevant confounders.ResultsAmong 153 eligible patients, 107 (69.9%) achieved pCR. Patients with pCR had significantly higher carboplatin exposure compared with those without pCR. RCS analysis demonstrated a significant linear dose–response relationship between carboplatin dAUC and pCR probability (overall trend p = 0.050; non-linearity p = 0.114), with an exploratory exposure threshold of 5.49 mg min/mL. Multivariable logistic regression confirmed that higher carboplatin exposure, as measured by dAUC, was independently associated with reduced odds of achieving non-pCR. However, excessively high carboplatin exposure was significantly associated with an elevated risk of thrombocytopenia, while patients who experienced liver injury exhibited lower carboplatin exposure.ConclusionCarboplatin exposure showed a linear association with pCR in patients receiving the TCbHP neoadjuvant regimen. Low exploratory exposure (5.49 mg min/mL) may compromise treatment efficacy, while excessively high exposure may increase hematologic toxicity. These findings provide real-world evidence to support individualized carboplatin dosing strategies aimed at optimizing the efficacy–toxicity balance.
SN - 1663-9812
ER -