PDL-1 expression, the Cancer Genome Atlas (TCGA) Subtype and Mutational Load are independent predictors of response to atezolizumab in Metastatic Urothelial Carcinoma (mUC, IMvigor 210).

Hoffmann-La Roche
Study Design: 
Cohort 2 was a phase II study of patients who had received >1 platinum containing regimens. The results have been published (Rosenberg JE et al Lancet. 2016 May 7;387(10031):1909-20) leading to FDA approval of atezolizumab in metastatic urothelial cancer refractory to standard chemotherapy
Immunologic correlates corresponding to the TCGA Subgroups were evaluated and updated at ASCO (Rosenberg JE et al).
It was shown that PDL-1 status, TCGA subgroup (particularly the luminal subgroup) and mutational load were independently associated with response to atezolizumab. The luminal subgroup was associated with a more inflamed environment than the basal subtype. The luminal subtype was also found to have high Teff cells and low stromal gene expression. Assessment of these characteristics may define drivers of immune responses. Further work on the biology of immune response to checkpoint inhibits is clearly a priority.