Tailored Dose-Dense Chemotherapy Improved Survival Outcomes Among Patients With High-Risk Early Breast Cancer

Results From the Phase 3 PANTHER Trial 

According to end of study results from the phase 3 PANTHER trial, tailored and dose-dense chemotherapy in the adjuvant setting improved survival outcomes compared to standard chemotherapy among patients with high-risk early breast cancer. 

“The dose-dense sequential administration of an anthracycline and a taxane after surgery for early breast cancer reduces breast cancer recurrence and mortality, with the same relative risk reduction regardless of clinical and pathologic factors,” stated Alexios Matikas, MD, PhD, Karolinska Comprehensive Cancer Center, Stockholm, Sweden, and coauthors. “However, the relative effect of the administered drugs is unknown.”

In this trial, 2003 patients with nonmetastatic, high-risk early breast cancer who underwent surgical resection were assigned to receive epirubicin and cyclophosphamide once every 2 weeks for 4 cycles followed by 4 cycles of docetaxel once every 2 weeks (n = 1001), or fluorouracil and endocrine therapy once every 3 weeks for 3 cycles followed by 3 cycles of docetaxel once every 3 weeks (n = 1002). Primary end points included breast cancer recurrence-free survival (RFS), event-free survival (EFS), distant disease-free survival (DFS), and overall survival (OS). 

At a median follow-up of 10.3 years there were 179 breast cancer relapses in the experimental arm and 218 breast cancer relapses in the control arm. RFS rate was 18.6% in the experimental arm and 22.3% in the control arm (hazard ratio [HR] 0.80; 95% confidence interval [CI], 0.65 to 0.88; P = .030). EFS rate was 23.2% in the experimental arm and 27.6% in the control arm (HR 0.78; 95% CI, 0.65 to 0.94; P = .009), and distant DFS rate was 17.2% and 20.9%, respectively (HR 0.79; 95% CI, 0.64 to 0.98 P = .030). Ten-year OS rate was 15.1% in the experimental arm and 16.6% in the control arm (HR 0.82; 95% CI, 0.65 to 1.04; P = .109). At the end of the study, 137 deaths had occurred in the experimental arm and 166 deaths had occurred in the control arm. 

As Dr Matikas et al concluded, “This is to our knowledge the first trial demonstrating improved outcomes with dose-dense chemotherapy when compared with a control of optimally dosed sequential [endocrine therapy] and docetaxel once every 3 weeks.” 

Source:

Matikas A, Möbus V, Greil R, et al. Tailored dose-dense versus standard adjuvant chemotherapy for high-risk early breast cancer: End-of-study results of the randomized PANTHER trial. J Clin Oncol. Published online: July 17, 2024. doi: 10.1200/JCO.24.00178