In an analysis from a phase II European trial reported in JAMA Oncology, Jens Huober, MD, and colleagues found no difference in overall survival with pertuzumab/trastuzumab, with or without chemotherapy, followed by second-line ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer.
Study Details
The open-label trial included 210 patients from sites in France, Switzerland, the Netherlands, and Germany. They were randomly assigned between May 2013 and January 2016 to receive pertuzumab/trastuzumab every 3 weeks without (n = 105) or with (n = 105) paclitaxel or vinorelbine for 4 months, followed by pertuzumab/trastuzumab maintenance after chemotherapy discontinuation. Patients in each group received T-DM1 at disease progression. A primary outcome measure was 2-year overall survival.
Jens Huober, MD
Key Findings
Overall survival at 24 months was 79.0% (90% confidence interval [CI] = 71.4%–85.4%) in the pertuzumab/trastuzumab group vs 78.1% (90% CI = 70.4%–84.5%) in the pertuzumab/trastuzumab plus chemotherapy group. Rates at 3, 4, and 5 years were 70.4% vs 73.2%, 56.0% vs 66.0%, and 50.7% vs 60.4%.
Median progression-free survival for first-line treatment was 8.4 months (95% CI = 7.9–12.0 months) in the pertuzumab/trastuzumab group vs 23.3 months (95% CI = 18.9–33.1 months) in the pertuzumab/trastuzumab plus chemotherapy group. A total of 64 patients in the pertuzumab/trastuzumab group and 47 in the pertuzumab/trastuzumab plus chemotherapy group received second-line T-DM1. Median progression-free during second-line treatment was 8.9 months (95% CI = 4.4–11.7 months) in the pertuzumab/trastuzumab group vs 6.4 months (95% CI = 4.0–12.7 months) in the pertuzumab/trastuzumab plus chemotherapy group.
No marked differences in overall or progression-free survival were observed between populations with HER2-enriched vs HER2-nonenriched cancers (as determined by the PAM50 test).
Apart from hematologic toxicity, most adverse events were grade 1 or 2, with almost all being more common in the chemotherapy group.
The investigators concluded, “The findings of this secondary analysis of a randomized clinical trial suggest that the chemotherapy-free anti-[HER2] strategy is feasible without being detrimental in terms of overall survival. The 50-gene prediction analysis of microarray signature could not help to identify the most appropriate patient population for this approach.”
Dr. Huober, of the Breast Center St. Gallen, Cantonal Hospital St. Gallen, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by F. Hoffmann–La Roche AG, Swiss Cancer Research Foundation, Swiss Cancer League, and others. For full disclosures of the study authors, visit jamanetwork.com.
