A Phase III, Randomized, Double-Blind, Placebo-Controlled Registration Trial to Evaluate the Efficacy and Safety of Placebo + Trastuzumab + Docetaxel vs. Pertuzumab + Trastuzumab + Docetaxel in Patients with Previously Untreated HER2-Positive Metastatic Breast Cancer (CLEOPATRA) J Baselga, J Cortés, S-B Kim, S-A Im, R Hegg, Y-H Im, L Roman, J L Pedrini, T Pienkowski, A Knott, E Clark, M C. Benyunes, G Ross, and S M Swain 1. Baselga et al. N Engl J Med 2011
A Phase III, Randomized, Double-Blind, Placebo-Controlled Registration Trial to Evaluate the Efficacy and Safety of Placebo + Trastuzumab + Docetaxel vs. Pertuzumab + Trastuzumab + Docetaxel in Patients with Previously Untreated HER2-Positive Metastatic Breast Cancer (CLEOPATRA). - PowerPoint PPT Presentation
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
A Phase III, Randomized, Double-Blind, Placebo-Controlled Registration Trial to Evaluate the Efficacy and Safety of Placebo + Trastuzumab + Docetaxel vs.Pertuzumab + Trastuzumab + Docetaxelin Patients with Previously Untreated HER2-Positive Metastatic Breast Cancer (CLEOPATRA)
J Baselga, J Cortés, S-B Kim, S-A Im,
R Hegg, Y-H Im, L Roman, J L Pedrini, T Pienkowski, A Knott, E Clark, M C. Benyunes, G Ross, and S M Swain
1. Baselga et al. N Engl J Med 2011
2HER2, human epidermal growth factor receptor 2;MBC, metastatic breast cancer
1. Slamon et al. N Engl J Med 2001; 2. Nahta & Esteva Oncogene 2007;3. Franklin et al. Cancer Cell 2004; 4. Baselga et al. J Clin Oncol 2010;
5. Gianni et al. Cancer Res 2010 Suppl 2; 6. Baselga & Swain Clin Breast Cancer 2010
Introduction and study objective
• Trastuzumab-based therapy is the current standard of care inHER2-positive MBC1
– However, progression of breast cancer still occurs in a majority of patients2
• Pertuzumab is a humanized monoclonal antibody and HER2 dimerization inhibitor that binds HER2 at a different epitope than trastuzumab3
• Phase II trials in patients with HER2-positive breast cancer have shown improved activity, and a good safety profile with pertuzumab-trastuzumab-based therapy4,5
• CLEOPATRA assessed efficacy and safety of a pertuzumab-trastuzumab-based regimen in first-line treatment of patients with HER2-positive MBC6
3
Study design
MBC, metastatic breast cancer; PD, progressive disease
Patients withHER2-positive MBCcentrally confirmed
(N=808)
Placebo + trastuzumab
1:1
• Randomization was stratified by geographic region and prior treatment status (neo/adjuvant chemotherapy received or not)
• Study dosing q3w:- Pertuzumab/Placebo: 840 mg loading dose, 420 mg maintenance- Trastuzumab: 8 mg/kg loading dose, 6 mg/kg maintenance - Docetaxel: 75 mg/m2, escalating to 100 mg/m2 if tolerated
Docetaxel*≥6 cycles
recommended
n=406
n=402
Pertuzumab + trastuzumab
Docetaxel*≥6 cycles
recommended
*<6 cycles allowed for unacceptable toxicity or PD; >6 cycles allowed at investigator discretion
PD
PD
4
Key patient eligibility criteria
• Centrally confirmed HER2-positive (IHC 3+ and/or FISH-positive; ratio ≥2.0) locally recurrent, unresectable, or metastatic breast cancer
• Measurable and/or non-measurable disease
• LVEF ≥50% at baseline
• No more than one hormonal regimen for MBC prior to randomization
• (Neo)adjuvant systemic breast cancer chemotherapy including trastuzumab and/or taxanes allowed if followed by a disease-free interval of ≥12 months
• No history of CHF or LVEF decline to <50% during or after prior trastuzumab therapy
CHF, congestive heart failure; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; LVEF, left ventricular ejection fraction;MBC, metastatic breast cancer
• Secondary endpoints– Overall survival– Objective response rate– Safety– PFS by investigator assessment– Duration of response– Evaluation of biomarkers and correlation with clinical
outcomes– Time to symptom progression
Baselga et al. Clin Breast Cancer 2010.
6
Statistics
• Progression-free survival– 800 patients and ~381 PFS events were required to
provide 80% power to detect a 33% improvement in independently assessed PFS(HR = 0.75) at the two-sided significance level of 5%
• Overall survival– 800 patients and 385 OS events were required to provide
80% power to detect a 33% improvement in OS (HR = 0.75) at the two-sided significance level of 5%
– The interim OS analysis (estimated at 50% of events for final analysis) was planned at the time of the primary independently assessed PFS analysis
• The combination of pertuzumab with trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects.