None of the 19 potential biomarkers assessed in an exploratory study were found to help select which patients with HER2-positive metastatic breast cancer would benefit most from treatment with the monoclonal anti-HER2 antibody pertuzumab – other than the HER2 biomarker already in use for that purpose, according to a report published online Oct. 27 in Journal of Clinical Oncology.
Even though anti-HER2 therapies for metastatic breast cancer have been in use for more than 15 years, HER2 status itself remains the only marker of sensitivity to those agents, and it is an imperfect one. “We therefore aimed to explore within the HER2-positive patient population whether subgroups that derive differential progression-free survival or overall survival benefit from HER2-targeted treatment can be identified based on biomarker profiles,” said Dr. José Baselga, physician in chief and chief medical officer at Memorial Sloan Kettering Cancer Center, New York, and his associates.
They analyzed tumor, serum, and whole blood samples from 808 participants in a phase III randomized clinical trial assessing response to pertuzumab and trastuzumab therapy. These patients had locally recurrent nonresectable or metastatic breast cancer and had not received any chemotherapy. Each tissue sample was tested using a panel of 19 potentially useful biomarkers thought to be involved in either resistance to HER2-targeted agents or regulation of HER2-signaling pathways, the investigators said (J. Clin. Oncol. 2014 Oct. 27 [doi:10.1200/JCO.2013.54.5384]).
None of the biomarkers were found to correlate with treatment response, as measured by the patients’ progression-free and overall survival. One biomarker, a mutation in the PIK3CA gene, appeared to identify tumors that would not respond well to pertuzumab even though they expressed HER2, but further study of this possible association is needed, Dr. Baselga and his associates said.