Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer

Abstract

BACKGROUND Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)–positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. METHODS We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease–free survival rate of 91.8% with pertuzumab and 89.2% with placebo. RESULTS In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor–negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P= 0.045). The estimates of the 3-year rates of invasive-disease–free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease–free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P= 0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease–free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P = 0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%). CONCLUSIONS Pertuzumab significantly improved the rates of invasive-disease–free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo.

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

“…Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2‐positive Metastatic Breast Cancer) trial, the addition of pertuzumab to trastuzumab and chemotherapy led to dramatic improvements in overall and progression‐free survival of patients with metastatic HER2‐positive breast cancer 8. Additionally, pertuzumab is approved for use in the neoadjuvant setting in patients with early breast cancer, and a large trial evaluating its use in the adjuvant setting in combination with trastuzumab has recently reported favorable outcomes 30, 31, 32. The use of lapatinib and ado‐trastuzumab emtansine is restricted to patients with disease progression on trastuzumab in the metastatic setting 33.…”

Cancer treatment associated cardiac toxicities

“…[28][29][30]32 Pertuzumab is a newer recombinant monoclonal antibody that is used in combination with trastuzumab as neoadjuvant therapy to limit the dimerization of the HER2 receptor with other HER receptors. [36][37][38] Dual therapy against the HER2 receptor shown to decrease disease progression and increase survival. [36][37][38] However, the addition of pertuzumab has not been shown to increase cardiac toxicity when compared to trastuzumab therapy alone, with the majority of the events being both reversible and clinically manageable.…”

“…[36][37][38] Dual therapy against the HER2 receptor shown to decrease disease progression and increase survival. [36][37][38] However, the addition of pertuzumab has not been shown to increase cardiac toxicity when compared to trastuzumab therapy alone, with the majority of the events being both reversible and clinically manageable. [36][37][38] According to the United States Food and Drug Administration guidelines, patients treated with pertuzumab are recommended to have LVEF evaluated at the beginning of treatment and every 3 months for individuals with metastatic disease and every 6 weeks for those undergoing neoadjuvant treatment.…”

Application of omic technologies in cancer research

“…[1][2][3] Altered expression of three breast cancer associated receptors (ER, PR, HER2) are also present in breast cancer, 4,5 and these can act as targets for therapeutics such as Trastuzumab and Trastuzumab emtansine which bind to HER2. 6,7 Another area which has attracted a great deal of interest in the recent past relates to microRNA (miRNA), which are small non-coding RNA molecules of about 22 nucleotides in length. An example of this are the miR-141 and miR-375, which have been detected at significantly greater levels in metastatic compared to non-metastatic prostate cancer.…”