Immunotherapy for GU Ca: A primer for urologists
Immunotherapy for the genitourinary cancers is a very active area of research. For prostate cancer, the investigational pipeline of immunotherapies includes other therapeutic vaccines, and CPIs are also being studied in clinical trials.
The relative lag in development of CPI treatment for prostate cancer may be explained in part by an early finding that PD-L1 was not highly expressed on CRPC specimens. Therefore, it was reasoned that antibodies targeting the PD-1/PD-L1 axis would not be effective, said Dr. Petrylak.
In an early pilot study investigating nivolumab as treatment for mCRPC, there were no objective responses observed among the 17 enrolled patients who were all heavily pretreated.
The commercially available CTLA-4 antibody, ipilimumab (Yervoy), was also investigated as treatment for mCRPC in two phase III trials, one enrolling patients prior to docetaxel (Taxotere) and the other after docetaxel failure, but no survival benefit was seen. In a post hoc analysis in the post-docetaxel chemotherapy trial, however, improved survival was seen with ipilimumab versus placebo in men who had boney, non-visceral metastases.
Benefit was also observed in men with enzalutamide (XTANDI)-resistant mCRPC in a study investigating pembrolizumab, which is an anti-PD-1 antibody like nivolumab. Upregulation of PD-L1 expression by enzalutamide is one possible explanation for the antitumor activity that was observed with pembrolizumab, Dr. Petrylak said.
Ongoing trials for mCRPC are investigating CPIs as single agents and in combination with available treatments (eg, radium 223 [Xofigo] or enzalutamide). There are also trials evaluating sipuleucel-T combined with approved drugs (eg, abiraterone acetate [Zytiga], enzalutamide, radium 223) or with a CPI.
Similarly, studies are evaluating a CPI combined with agents from another therapeutic class (eg, chemotherapy, investigational molecules targeting pathways regulating immunotherapy resistance, targeted small molecules) as treatment for UC and RCC.
“Studies of combination approaches using immunotherapy for UC and RCC include those exploring what appears to be an interesting interplay between angiogenesis and immunotherapy,” Dr. Petrylak said.
Combinations of CPIs that target different checkpoint axes are also being investigated for mRCC and prostate cancer.
“The combination of ipilimumab and nivolumab is already approved for the treatment of metastatic melanoma,” Dr. Kim said.
CPIs targeting novel checkpoints, such as lymphocyte activation gene-3, are also in clinical trials for UC and RCC.
In addition, ongoing research with the available immunotherapies for genitourinary malignancies is examining genomic and other potential predictors for response.