Kristi Tinsbloom, PharmD candidate 2015, Mercer University College of Pharmacy
Breast cancer is the second leading cause of cancer death in American women; it is the most common site of cancer. In 2013, approximately 40,000 people in the United States died from breast cancer. Diagnosis of breast cancer is most often made at an early stage, which means tumors are smaller in size and localized to breast tissue. However, if breast cancer is categorized as stage IV, it is indicative of metastatic disease and the 5-year survival rate is estimated to be 23%.1
The human epidermal growth factor receptor 2 (HER2) gene when overexpressed is associated with increased tumor aggressiveness, recurrence rates, and mortality rates.1 Overexpression of HER2 occurs in approximately 15% to 20% of patients that have invasive breast cancer. According to the American Society of Clinical Oncology (ASCO) guideline for HER2-positive metastatic breast cancer, recommended first-line treatment is a combination of the monoclonal antibodies pertuzumab and trastuzumab, as well as a taxane chemotherapeutic agent.2 A recently published study details patient survival rates when treated with the recommended first-line combination.3
|Title: Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer3|
|Design||Randomized, double-blind, placebo-controlled; 808 participants|
|Objective||To assess overall survival of patients with HER2-positive metastatic breast cancer|
|Study groups||Two groups:
• pertuzumab, trastuzumab, and docetaxel
• placebo, trastuzumab, and docetaxel
|Methods||Participants were enrolled with locally recurrent, unresectable, or metastatic HER2-positive breast cancer. Participants were eligible if they had > 50% left ventricular ejection fraction (LVEF) at baseline and had received no more than one hormonal treatment for metastatic disease. This trial is a continuation of the CLEOPATRA trial, which showed that progression-free survival was significantly improved with pertuzumab, trastuzumab, and docetaxel compared with placebo, trastuzumab, and docetaxel. This study reports updated data on the secondary end points of overall survival from the CLEOPATRA trial.|
|Duration||February 12, 2008 through July 7, 2010||Primary Outcome Measure||Overall survival (time from randomization to death from any cause)|
|Baseline Characteristics||All patients:
• Had not received previous chemotherapy or anti-HER2 therapy
• LVEF > 50%
• 18 years of age or older
• Had an Eastern Cooperative Oncology Group performance status of 0 or 1
|Results||The median overall survival was 56.5 months in the pertuzumab combination group compared with 40.8 months for the placebo combination group (hazard ratio 0.68, p<0.001).|
|Adverse Events||Common Adverse Events: nausea (pertuzumab 12.7%, placebo 11.5%), rash (pertuzumab 18.3%, placebo 8.0%), vomiting (pertuzumab 9.8%, placebo 6.5%), pruritus (pertuzumab 13.7%, placebo 5.7%), myalgia (pertuzumab 8.2%, placebo 7.3%), peripheral edema (pertuzumab 9.2%, placebo 12.3%), diarrhea (pertuzumab 28.1%, placebo 14.2%)
*The adverse events above reflect data obtained after the discontinuation of docetaxel in the study.
|Serious Adverse Events: N/A|
|Percentage that Discontinued due to Adverse Events: pertuzumab combination group (9%) and placebo combination (10%)|
|Study Author Conclusions||The addition of pertuzumab to trastuzumab and docetaxel in patients with HER2-positive metastatic breast cancer significantly improved the medial overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this combination.|
The results of this study are compelling in that the addition of pertuzumab to the trastuzumab plus docetaxel regimen extends survival by a little more than 15 months on average. This is a significant increase in overall survival for patients with advanced disease and poor prognosis.
1. Barnett CM, Michaud L, Esteva FJ. Chapter 105. Breast Cancer. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=48811500 Accessed March 05, 2015.
2. Treatment of Metastatic HER2-Positive Breast Cancer. http://www.cancer.net/ research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-her2-positive-breast-cancer. Accessed March 5, 2015.
3. Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724-34.