ASCO 2016 Update: Biomarker-Based Strategies

Why does immunotherapy work in a subset of cancer patients, but not in others? This pressing question is the focus of intense research aimed at identifying signals, called biomarkers, that may potentially indicate which patients are likely to respond to immunotherapy and which aren’t. While many of the talks here at ASCO’s annual meeting explore the significance of biomarkers, three presentations stood out.  

Dung Le, MD, of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, presented data from a study she conducted in collaboration with colleague Luis Diaz, MD, that explored the effectiveness of Merck’s pembrolizumab in solid tumors lacking DNA-repair capabilities. Previous trials have shown that patients with repair-deficient colorectal cancer (CRC) responded to pembrolizumab. This study showed that patients with other repair-deficient, non-CRC cancers such as gastric, pancreatic, and prostate cancers could also be treated effectively this way.

Work by Thomas Gajewski, MD, PhD, of The University of Chicago Medicine and a member of CRI’s Scientific Advisory Council, next showed that activity of a pathway called Wnt/b-catenin was associated with the exclusion of immune cells in “cold” tumors. This indicates that perhaps inactivating that pathway could be key to improving immunotherapy’s effectiveness.

Lastly, Samuel Funt, MD, of Memorial Sloan Kettering Cancer Center, revealed that, in bladder cancer patients treated with atezolizumab (for which it received FDA approval last month), those who responded were far more likely to have a diverse repertoire of T cell receptors (TCR) in their blood, but a more uniform TCR repertoire in their tumors. Responsive patients also exhibited a rapid and robust expansion of T cells in their blood during treatment, reflecting the ongoing anti-tumor response.