Is there any data on the use of PARP inhibitors in patients with metastatic urothelial carcinoma with deleterious DDR mutations?
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Bradley McGregor
Dana-Farber Cancer Institute
This is an evolving field. While the thought had been all the drugs were likely equivalent in efficacy (with no head to head trials) this has changed in the past week. Roche had a press release in which they announced the Phase III IMvigor211 study that evaluated atezolizumab in people with locally advanced or metastatic urothelial cancer (mUC) whose disease progressed during or after treatment with a platinum-based chemotherapy (previously treated) did not meet its primary endpoint of overall...
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Min Yuen Teo
Memorial Sloan Kettering Cancer Center
Our recent work showed that urothelial cancers harbor high rate of alterations in DDR (DNA damage repair and response) genes, with 25 – 29% rate of deleterious alterations and up to 25% with variants of unknown significance – considering the genomic complexity of urothelial cancers, it is not unreasonable to postulate that some of these variants of unknown significance might be functionally significant. We have also shown that DDR alterations are associated wi...
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Min Yuen Teo
Memorial Sloan Kettering Cancer Center
Urothelial cancers harbor high rate of deleterious DDR alterations. Based on clinical data from other tumor types, especially TOPARP-A in metastatic castration-resistant prostate cancer where responses to olaparib monotherapy were observed especially among men with defective DDR genes, the use of PARP inhibitors appears to be an attractive therapeutic strategy for urothelial cancer. There are no reported trials or case reports to date with regards to clinical activities, however, it is an area o...
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Urothelial cancers harbor high rate of deleterious DDR alterations. Based on clinical data from other tumor types, especially TOPARP-A in metastatic castration-resistant prostate cancer where responses to olaparib monotherapy were observed especially among men with defective DDR genes, the use of PARP inhibitors appears to be an attractive therapeutic strategy for urothelial cancer. There are no reported trials or case reports to date with regards to clinical activities, however, it is an area of active research, with on-going clinical trials. These include the phase II ATLAS trial, a single-arm study of rucaparib in platinum- and/or immunotherapy-refractory advanced urothelial cancer (NCT03397394) and BAYOU, a randomized phase II trial of durvalumab + olaparib/placebo in cisplatin-ineligible advanced urothelial cancers (NCT03459846). The results of these studies will be informative and might further redefine the therapeutic landscape of urothelial cancers.