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Kidney Cancer Symposium 2017: PBRM1/BAP1 Mutations and TKI Response in Kidney Cancer

By: Celeste L. Dixon
Posted: Monday, November 20, 2017

Mutations of the PBRM1 and BAP1 genes appear to affect response to treatment with tyrosine kinase inhibitors (TKIs) for advanced renal cell carcinoma in opposite ways, according to a presentation at the 2017 International Kidney Cancer Symposium in Miami. These findings may have clinical implications in the selection of appropriate therapies in this patient population.

“Loss of PBRM1 enhances the proangiogenic microenvironment of renal cell carcinoma with favorable effects on response to TKI; BAP1 loss associates with decreased angiogenic signaling and adverse outcome to TKI,” wrote lead investigator Martin Henner Voss, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues in the abstract’s conclusion.

The investigators completed an integrated biomarker analysis of 412 patients with renal cell carcinoma participating in the phase III COMPARZ trial who were treated with either of two TKIs: sunitinib or pazopanib. In the 377 patients evaluated, those with PBRM1 mutation had higher progression-free and overall survival than did those with PBRM1 wild-type disease (11.04 vs. 8.25 months; 35.48 vs. 26.12 months, respectively). However, patients with BAP1 mutations had inferior progression-free and overall survival compared with those with wild-type BAP1 (5.52 vs. 10.68 months; 21.78 vs. 31.61 months, respectively).

In renal cell carcinoma, mutations in PBRM1 and BAP1 are quite common and usually do not overlap. Of the 412 patients in this analysis, 44% and 15% had PBRM1 and BAP1 mutations, respectively.