DNA repair gene mutations predict response to anti–PD-1/PD-L1 in urothelial cancer

Previous studies have shown that in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy, alterations in DDR genes are associated with elevations in mutational load, increases in tumor-infiltrating lymphocytes, and improved survival, the investigators noted.

To see whether DDR gene alterations were also associated with better outcomes with PD-1/PD-L1 inhibitors, the investigators examined tumor genomes and survival data from patients with metastatic urothelial carcinoma who were enrolled in prospective clinical trials of anti–PD-1/PD-L1 monotherapy. The agents used in the trials were atezolizumab(Tecentriq) and nivolumab(Opdivo).

The investigators correlated the presence of DDR gene alterations with best objective responses according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1.

They found that the presence of any DDR gene alteration was associated with higher response rates, compared with wild-type DDR (67.9% vs. 18.8%; P less than .001).