Tailored Dose-Dense Chemotherapy Improves Event-free Survival in High-Risk Breast Cancer

Share this content:
Tailored Dose-Dense Chemotherapy Improves Event-free Survival in High-Risk Breast Cancer
Tailored Dose-Dense Chemotherapy Improves Event-free Survival in High-Risk Breast Cancer

CHICAGO — Tailored dose-dense chemotherapy significantly improved event-free survival and also showed efficacy in relapse-free and overall survival compared with standard adjuvant chemotherapy in patients with high-risk breast cancer, according to results of the phase 3 PANTHER study reported at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.

In addition, “the superiority of tailored dose-dense epirubicin plus cyclophosphamide and docetaxel was consistent in all studied subgroups, including estrogen-receptor positive and HER2-positive disease treated with trastuzumab,” said Prof. Jonas C. S. Bergh, Karolinska Institutet, Karolinska University Hospital and SweBCG, Stockholm, Sweden.

“Chemotherapy remains a cornerstone for breast cancer management, likely for many years to come — why not use the drugs slightly better, as described in the PANTHER study?” he asked?

Noting that standard dosing of chemotherapy based on body surface area — a formula established in 1916 on 9 patients — results in marked interpatient variation in pharmacokinetics, toxicities, and efficacy, the PANTHER study randomly assigned 2017 patients with node-positive or high-risk node-negative breast cancer in 86 centers in Sweden, Austria, and Germany between February 2007 and September 2011 1:1 to one of two arms.

In the tailored dose-dense arm, patients received 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin 38-120 mg/m2 (starting at 90 mg/m2) and cyclophosphamide 450-1200 mg/m2 (starting at 600 mg/m2) every 2 weeks, followed by 4 cycles of docetaxel 75-100 mg/m2 (starting at 75 mg/m2) every 2 weeks, with a 3-week pause between epirubicin/cyclophosphamide and docetaxel.

In the control arm, they received 3 cycles of standard 5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2 every 3 weeks followed by 3 cycles of docetaxel 100 mg/m2 every 3 weeks.

Total treatment duration was the same in the 2 arms. The primary end point was breast cancer relapse-free survival assessed in the intention to treat population. Secondary end points included event-free survival and overall survival.

At a median follow-up of 5.3 years, 269 breast cancer relapse-free survival events were reported, 118 in the tailored dose-dense arm, and 151 in the control arm (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.61-1.012; P = .062 by log-rank test).

The 5-year breast cancer relapse-free survival was 88.7% in the tailored dose-dense arm and 85% in the control arm, a 3% gain, Prof. Bergh said.

Patients in the tailored dose-dense arm had significantly better event-free survival (HR, 0.79; 95% CI, 0.63-0.99; P = .042); the 5-year rates were 86.7% versus 82.1%, a 4.6% gain. Also observed was a trend to better overall survival in the tailored dose-dense arm (HR, 0.77; 95% CI, 0.57-1.05; P = .093); the 5-year overall survival rates were 92.1% vs 90.2%, a 1.9% gain.

No significant interactions were found in predefined subgroups, including patients with hormone receptor-positive disease or those treated with trastuzumab.

Grade 3/4 hematologic toxicity was higher in the tailored dose-dense arm compared with the control arm, 93% vs 21%. Five cases of myelodysplastic syndrome/acute myeloid leukemia were reported, 3 in the TDD arm and 2 in the control arm.



1. Bergh JC, Foukakis T, von Minckwitz G, et al. PANTHER: Prospective randomized phase III trial of tailored and dose-dense versus standard tri-weekly adjuvant chemotherapy for high-risk breast cancer in the modern era of endocrine and anti-HER2 therapy. Oral presentation at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL.

You must be a registered member of ONA to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings


Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Genitourinary Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Rare Cancers Regimens
Skin Cancer Regimens Drugs