, according to a gene expression analysis.
Nicholas C. Turner, MD, PhD, of Royal Marsden Hospital and Institute of Cancer Research in London, and his colleagues used a gene expression panel to detect biomarkers related to the efficacy of palbociclib plus fulvestrant in patients with endocrine-pretreated metastatic breast cancer.
“No predictive biomarkers have been identified in randomized trials of CDK4/6 inhibitors,” the researchers wrote in the Journal of Clinical Oncology.
Study participants were randomly assigned to receive either combination palbociclib and fulvestrant (n = 194) or placebo and fulvestrant (n = 108). The primary analysis was completed using data from the PALOMA-3 trial, which included 10 genes selected from a panel search of 2,534 genes.
The association between level of gene expression and efficacy of palbociclib combination therapy was evaluated by way of advanced statistical analysis.
After analysis, the efficacy of palbociclib was found to be reduced with high levels of cyclin E1 mRNA expression compared with low levels (median PFS palbociclib arm, 7.6 vs. 14.1 months; placebo arm, 4.0 vs. 4.8 months; P = .00238).
“These data suggest that CCNE1 mRNA expression may be associated with the benefit from palbociclib in early-stage breast cancer,” they wrote.
The authors acknowledged that one key limitation of the study was that the biomarkers identified may not be relevant to other CDK4/6 inhibitor combinations.
“Additional methodologic and clinical validations are warranted to elucidate the role of CCNE1 mRNA expression as a biomarker of CDK4/6 inhibitor therapy,” they concluded.
The study was supported by Pfizer. The authors reported financial interests with AbbVie, AstraZeneca, Genentech, Novartis, Pfizer, and others.
SOURCE: Turner NC et al. J Clin Oncol. 2019 Feb 26. doi: 10.1200/JCO.18.00925.