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.

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“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.