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

Additionally, patients whose tumors contained known or likely deleterious DDR mutations were significantly more likely to respond than were patients with either mutations of uncertain significance or wild-type DDR (overall response rate 80%, 54%, and 19%, respectively; P less than .001).

Patients with deleterious DDR alterations had significantly better PFS than patients without detectable alterations (hazard ratio, 0.20; P less than .001); DDR mutations of unknown significance trended toward better PFS (HR, 0.44), but was not statistically significant.

Median OS was not reached for patients with deleterious DDR gene mutations, with 71.5% alive at 12 months, compared with a median of 23 months for patients with alterations of unknown significance, and 9.3 months for patients with wild-type DDR.

In multivariable analysis, independent predictors for worse OS included hemoglobin levels below 10 g/dL and visceral metastases. In contrast, any versus no detectable DDR gene alterations was associated with better OS (HR, 0.27; P = .001).