CLEOPATRA Analysis Shows That HER2 Is Sole Marker Suitable for Selection of Pertuzumab/Trastuzumab-Based Treatment in Metastatic Breast Cancer
In an analysis in the CLEOPATRA trial population reported in the Journal of Clinical Oncology, Baselga et al found that HER2 was the only biomarker suitable for use in selecting patients for first-line pertuzumab (Perjeta)/trastuzumab (Herceptin)-based treatment in patients with HER2-positive metastatic breast cancer.
Study Details
The study involved analysis of mandatory tumor and serum samples from 808 patients receiving first-line pertuzumab, trastuzumab, and docetaxel vs trastuzumab and docetaxel in CLEOPATRA. Samples were assessed (58%–99.8% assessable) for amphiregulin, betacellulin, EGF, transforming growth factor alpha, EGFR, HER2, HER3, insulin-like growth factor 1 receptor, PTEN, phosphorylated AKT, PIK3CA, CMYC, serum HER2 extracellular domain (sHER2), and FCγR. The CLEOPATRA trial showed significant increases in progression-free survival and overall survival with the addition of pertuzumab.
Prognostic Markers
A consistent benefit of pertuzumab was observed independent of biomarker subgroup (hazard ratios [HRs] < 1.0, most of which were significant), including estrogen receptor–negative and –positive subgroups. Overall, the progression-free survival benefit was larger in estrogen receptor–negative patients (HR = 0.55, 95% confidence interval [CI] = 0.42–0.72) than in estrogen receptor–positive patients (HR = 0.72, 95% CI = 0.55–0.95).
With regard to individual biomarkers, significant beneficial prognostic effects were found for higher HER2 protein (P < .05), HER2 mRNA (P < .008), and HER3 mRNA (P < .03), wild-type PIK3CA mutation (P < .001), and lower sHER2 level (P = .04). PIK3CA status was associated with the greatest prognostic effect, with longer median progression-free survival for wild-type vs mutated PIK3CA being observed in both the pertuzumab (21.8 vs 12.5 months) and control groups (13.8 vs 8.6 months).
The investigators concluded: “Through comprehensive prospective analyses, CLEOPATRA biomarker data demonstrate that HER2 is the only marker suited for patient selection for the trastuzumab plus pertuzumab-based regimen in HER2-positive metastatic breast cancer. HER2, HER3, and PIK3CA were relevant prognostic factors.”
José Baselga, MD, PhD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article
The study was funded by F. Hoffmann-La Roche. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
