Effect of docetaxel duration on clinical outcomes: exploratory analysis of CLEOPATRA, a phase III randomized controlled trial

Abstract

Background

Combination pertuzumab, trastuzumab, and docetaxel (D) is considered standard first-line treatment for human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC). This post hoc, exploratory analysis of CLEOPATRA study data evaluated the clinical effects of D treatment duration within this regimen. The clinical benefits of pertuzumab and trastuzumab by different durations of D treatment were also evaluated.

Patients and methods

Patients with HER2-positive MBC received trastuzumab and D plus pertuzumab or placebo. Clinical outcomes were analyzed by the number of D cycles that patients received (<6D, 6D, or > 6D). Progression-free survival (PFS) and overall survival (OS) for each treatment arm within each D cycle group were estimated using the Kaplan–Meier approach. Time-dependent, multivariate Cox regression was applied to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for HER2-targeted therapy and D cycle groups.

Results

Overall, 804 patients received <6D (n=119), 6D (n=210), or > 6D (n=475) cycles. After adjusting for pertuzumab benefits versus placebo (PFS HR = 0.61, 95% CI 0.51–0.74, P<0.0001; OS HR = 0.60, 95% CI, 0.49–0.74, P<0.0001), >6D versus 6D cycles was not associated with statistically significant improvements in PFS (HR = 0.80, 95% CI 0.63–1.01, P=0.0640) or OS (HR = 0.88, 95% CI 0.69–1.12, P=0.3073). Consistent improvements in PFS and OS were observed with pertuzumab versus placebo, irrespective of D duration. The HRs for PFS were 0.395, 0.615, and 0.633 for <6D, 6D, and >6D cycles, respectively (P<0.05 for all D cycle groups). Corresponding HRs for OS were 0.577, 0.700, and 0.612, respectively (P<0.05 for <6D and >6D).

Conclusions

After accounting for pertuzumab benefits, more than 6 cycles of D treatment was not associated with significant improvements in either PFS or OS compared with 6 cycles. The addition of pertuzumab to trastuzumab improved clinical outcomes versus trastuzumab plus placebo, regardless of D treatment duration.ClinicalTrials.gov identifier: NCT00567190