Pertuzumab significantly extends the life of patients with metastatic breast cancer
The final results of the CLEOPATRA clinical trial show that patients with HER2-positive metastatic breast cancer achieve 8-year overall survival of 37% with the targeted treatment combination of pertuzumab + trastuzumab + docetaxel.
Dual HER2 Blockade in Breast Cancer Treatment
Metastatic HER2-positive breast cancer was considered a very aggressive tumor with poor prognosis. Patient survival significantly improved after the discovery of trastuzumab, a monoclonal antibody targeting HER2 receptors. The CLEOPATRA clinical trial evaluated the efficacy and safety of adding a second HER2 blocker, the monoclonal antibody pertuzumab. Interim data analyses from this study showed that progression-free survival and overall survival were significantly higher in the pertuzumab group. Now, the final study results after 8 years of follow-up have been published.
Study Methodology
CLEOPATRA is an international double-blind, placebo-controlled, phase III randomized clinical trial, which included 808 adult patients with HER2-positive metastatic breast cancer. This was the first-line treatment for metastatic disease.
Patients were randomized in a 1:1 ratio to receive pertuzumab at an initial dose of 840 mg and then 420 mg every 3 weeks, or placebo. All patients also received trastuzumab at an initial dose of 8 mg/kg and then 6 mg/kg, and docetaxel at a dose of 75 mg/m2, potentially increasing to 100 mg/m2 if tolerated. Medications were administered intravenously every 3 weeks, with pertuzumab/placebo and trastuzumab administered until disease progression, and docetaxel for 6 cycles or longer at the discretion of the treating physician.
The primary aim of the study was to evaluate progression-free survival (PFS) – these results had already been published. Overall survival (OS) and safety profile were also assessed.
Results
The median OS in the pertuzumab group reached 57.1 months (95% confidence interval [CI] 50–72 months), compared to 40.8 months in the placebo group (95% CI 36–48 months; hazard ratio [HR] 0.69; 95% CI 0.58–0.82). 8-year overall survival was 37% (95% CI 31–42%) in the pertuzumab arm and 23% (95% CI 19–28%) in the placebo arm.
The most commonly observed grade 3–4 adverse event was neutropenia (49% of patients in the pertuzumab group, 46% in the placebo group). Treatment-related death was recorded in 5 patients treated with pertuzumab and 6 in the placebo arm. Since the previous data analysis, 1 case of congestive heart failure and 1 newly diagnosed case of left ventricular systolic dysfunction were observed in patients receiving pertuzumab.
Conclusion
The final analysis of the CLEOPATRA study shows that the previously observed improvement in overall survival with the combination treatment of pertuzumab, trastuzumab, and docetaxel vs. trastuzumab and docetaxel persisted throughout the more than 8-year follow-up period. The long-term safety profile, including cardiologic safety, was consistent with previous observations. The combination of pertuzumab + trastuzumab + docetaxel remains the standard for the first-line treatment of metastatic HER2-positive breast cancer.
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Source: Swain S. M., Miles D., Kim S.-B. et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol 2020 Apr; 21 (4): 519–530, doi: 10.1016/S1470-2045(19)30863-0.
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