From the Journals

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



Alterations in DNA damage response and repair genes may be useful biomarkers for response to immune checkpoint inhibitors in patients with urothelial carcinoma, investigators contend.

Among 60 patients with urothelial carcinoma in prospective trials of antibodies directed against the immune checkpoint inhibitor programmed cell death protein-1 and its ligand (PD-1/PD-L1), 28 (47%) had a damage response and repair (DDR) gene of any kind, and 15 (25%) had DDR mutations that are thought to be deleterious. Patients with any DDR mutations were more likely to have a clinical response to anti–PD-1/PD-L1 therapy, especially patients with likely deleterious mutations, reported Jonathan E. Rosenberg, MD and colleagues from Memorial Sloan Kettering Cancer Center, New York.

Dr. Jonathan E. Rosenberg

In addition to higher objective response rates, patients with DDR gene alterations had longer progression-free survival (PFS) and better overall survival (OS) than did patients with wild-type DDR genes, they noted in a study published in the Journal of Clinical Oncology.

“This study shows that patients with DDR gene alterations are more likely to experience objective responses, longer PFS, and improved OS than patients with wild-type DDR genes. Whether the association is predictive or prognostic should be investigated further in larger data sets from randomized studies that have led to the FDA [Food and Drug Administration] approval of several anti–PD-1/PD-L1 agents,” they wrote.


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