Investigators from the Dana-Farber Cancer Institute (Boston, MA, USA) have identified the serum-based protein angiopoietin-2 (ANGPT2) as a prognostic biomarker that could be utilized to predict clinical outcomes with patients with advanced melanoma and could identify those patients that might respond to immune checkpoint therapy.
Although immune checkpoint therapy has been proven as an effective treatment for a variety of different cancers, only some patients respond to these treatments. Therefore, the identification of the ANGPT2 protein is a significant step towards establishing why some patients respond to immune checkpoint therapy whilst others do not.
The team analyzed serum samples taken from patients with advanced melanoma who were undergoing immune checkpoint therapy from three clinical trials that had available survival data. The clinical trials were investigating different immune checkpoint inhibitors: ipilimumab; ipilimumab in combination with bevacizumab; and either nivolumab or pembrolizumab, which are both PD-1 inhibitors.
The study, published in Cancer Immunology Research, found in all three clinical trials that elevated concentrations of ANGPT2, observed in serum samples taken pre-treatment, correlated with a reduced overall survival. For the ipilimumab-only trial, which consisted of 48 patients, the medium overall survival for patients with elevated levels of ANGPT2 was 12.2 months, in comparison to 28.2 months for patients with low pre-treatment levels.
Similarly, the medium overall survival for patients with elevated levels of ANGPT2 for the 43 patients on the ipilimumab in combination with bevacizumab trial was 10.9 months, in comparison to 19.3 months for patients with low pre-treatment levels of ANGPT2.
The team also investigated the change in ANGPT2 concentrations from the samples taken prior to treatment and samples taken three months into the treatment. It was identified that patients from all three studies who had the largest increase in ANGPT2 levels also had a reduced overall survival. This correlation between the ANGPT2 protein and clinical outcomes supports the use of ANGPT2 as a prognosis biomarker for immune checkpoint therapy.
Sources: Wu X , Giobbie-Hurder A , Liao X et al. Angiopoietin-2 as a Biomarker and Target for Immune Checkpoint Therapy Cancer Immunol. Res. 5(1), 17-28 (2016); www.clinicaloncology.com/Current-Practice/Article/04-17/ANGPT2-Promising-Biomarker-for-Response/40938