Editor's Note: Numerous studies have confirmed the clinical value of postoperative adjuvant chemotherapy for early-stage breast cancer patients. However, the cardiotoxicity and hematologic adverse reactions associated with high-dose chemotherapy remain significant clinical challenges. Recently, the ESMO BC 2024 conference released the 10-year follow-up results of the PANTHER trial, an important study on the treatment of high-risk early breast cancer. This study revealed the efficacy differences between dose-dense tailored adjuvant chemotherapy and standard adjuvant chemotherapy, providing in-depth insights into the response of key subgroups. Oncology Frontier invited Professor Wenyan Chen from Nanchang People's Hospital to elaborate on the background, findings, clinical significance, and implications of this research.Key Findings from the ESMO BC Conference
The PANTHER trial, a phase III clinical study, reported 10-year follow-up results at the ESMO BC conference. From February 2007 to September 2011, 2003 patients were randomized into two groups. One group received dose-dense tailored adjuvant chemotherapy (tDD EC/D), and the other group received standard interval chemotherapy. With a median follow-up of 10.3 years, 179 breast cancer recurrences were observed in the experimental group compared to 218 in the control group. The tDD EC/D regimen improved the primary endpoint of breast cancer relapse-free survival (BCRFS) (HR=0.80, 95% CI: 0.65-0.98, P=0.030; 10-year event rate: 18.6% vs. 22.3%, absolute difference 3.7% ± 1.9%). BCRFS improvement was observed across various subgroups defined by hormone receptor and HER2 expression, anatomical staging, and other demographic and pathological factors. Notably, patients aged >50 years, hormone receptor-positive, and HER2-positive patients receiving trastuzumab showed significant benefits. No statistically significant difference was found in overall survival between the two groups (HR=0.82, 95% CI: 0.65-1.04, P=0.109; 10-year event rate: 15.1% vs. 16.6%, absolute difference 1.5% ± 1.7%). The conclusion drawn from the 10-year follow-up of the PANTHER trial indicated that dose-dense tailored adjuvant chemotherapy improved BCRFS compared to standard adjuvant chemotherapy with tri-weekly docetaxel.
Background and Significance
Since the advent of adjuvant chemotherapy, the exploration of dose-dense regimens has been ongoing. Before the PANTHER (PANTHER) study, the clinical value of postoperative adjuvant chemotherapy for early breast cancer patients had been well established. A 2012 meta-analysis published in The Lancet by the Early Breast Cancer Trialists’ Collaborative Group comprehensively summarized the value of adjuvant chemotherapy and the efficacy of different chemotherapy regimens for early breast cancer: 1) Adjuvant chemotherapy reduces the risk of death by one-third compared to no chemotherapy; 2) Sequential four cycles of taxane after standard anthracycline regimens significantly reduce the risk of death by 16%; 3) The higher the cumulative dose of anthracycline (≥240 mg/m² doxorubicin or ≥360 mg/m² epirubicin), the more significant the efficacy. However, higher doses of anthracycline also increase the risk of cardiotoxicity and secondary hematologic malignancies.
Dose-dense therapy refers to administering chemotherapy at shorter intervals without increasing the cumulative dose, which is considered a method to enhance treatment efficacy. The CALGB 9741 study published in JCO in 2003 indicated that a dose-dense two-week chemotherapy regimen could reduce the risk of recurrence by 26% compared to a three-week regimen for node-positive patients. Similar results were confirmed in a meta-analysis.
Moreover, chemotherapy doses are often calculated based on body surface area without considering factors such as age, weight, liver, and kidney function, leading to significant variability in drug clearance and adverse reactions among patients. Several clinical studies have suggested that adjusting chemotherapy doses based on patient adverse reactions as pharmacokinetic indicators could improve efficacy and positively correlate with hematologic adverse reactions. While dose-dense regimens show better efficacy, the short-term intensive administration may result in higher potential adverse reactions. Can we individualize the dosage of dose-dense regimens based on patient adverse reactions to ensure safety and further improve early breast cancer cure rates?
