A tailored dose-dense chemotherapy regimen has shown significant improvements in recurrence-free survival (RFS), event-free survival (EFS), and distant disease-free survival (DDFS) compared to standard adjuvant chemotherapy in patients with high-risk, early breast cancer. These findings come from the end-of-study results of the phase 3 PANTHER trial (NCT00798070). The study highlights a potential advancement in personalized treatment strategies for this patient population.
The study, published in the Journal of Clinical Oncology, is the first to confirm the benefit of a dose-dense regimen over a control regimen containing docetaxel administered once every three weeks, according to the authors.
Key Findings from the PANTHER Trial
With a median follow-up of 10.3 years (IQR, 9.1-10.5), the hazard ratio (HR) for RFS, the study’s primary endpoint, was 0.80 (95% CI, 0.65-0.98; P = .030). The 10-year event rate was 18.6% with the dose-dense regimen compared to 22.3% with standard chemotherapy. Secondary endpoints also showed significant improvements:
- EFS: HR, 0.78 (95% CI, 0.65-0.94; P = .009); 10-year event rates of 23.2% vs 27.6%
- DDFS: HR, 0.79 (95% CI, 0.64-0.98; P = .030); 10-year event rates of 17.2% vs 20.9%
These improvements were consistently observed across various patient subgroups.
Study Design and Patient Population
The phase 3, randomized PANTHER trial compared sequential epirubicin/cyclophosphamide and docetaxel administered either every two or three weeks. The dose-dense schedule allowed for tailored dosing based on hematologic toxicity, guided by a predefined algorithm. The trial enrolled 2017 patients, with 2003 included in the intention-to-treat analysis.
Patient characteristics were well-balanced between the two arms. The median age was 51.1 years (range, 23.3-69.2) in the experimental arm and 50.7 years (range, 21.4-68.6) in the standard chemotherapy arm. In the experimental arm, 3.1% of patients had 0 positive nodes, 59.0% had 1 to 3, 26.3% had 4 to 9, and 11.6% had more than 9. In the standard chemotherapy arm, these figures were 3.0%, 55.4%, 28.9%, and 12.7%, respectively. Furthermore, 80.4% of patients in the experimental arm were estrogen receptor- or progesterone receptor-positive, compared to 79.3% in the standard chemotherapy arm, while 16.0% and 18.2%, respectively, were HER2-positive.
Safety Profile
The final analysis of the PANTHER trial did not reveal any new safety concerns compared to the primary analysis. Notably, there were no reported cases of acute myeloid leukemia or myelodysplastic syndrome since the primary analysis, indicating a manageable safety profile for the tailored dose-dense regimen.
While the improvement in overall survival (OS) was not statistically significant (HR, 0.82; 95% CI, 0.65-1.04; P = .109), the 10-year event rate for OS was 15.1% with dose-dense treatment versus 16.6% with standard chemotherapy.
