“Clinically, the implications [of the THOR trial] are clear in that all metastatic urothelial cancers should be tested for FGFR mutations,” stated invited discussant Daniel P. Petrylak, MD, of Yale School of Medicine. “This should be done at the beginning of treatment for metastatic disease, as it takes time to get these tests back, and you want to be ready to offer the patient all treatment options when they experience disease progression.”

During his discussion, Dr. Petrylak noted there are no formal surveys about how many patients are presently being tested for FGFR mutations. However, he hopes it will become more widespread with these new data.

Daniel P. Petrylak, MD

Clinical Issues

The findings from THOR also raise the issue of how best to sequence and combine drugs for advanced urothelial cancer, including erdafitinib as well as the antibody-drug conjugates enfortumab vedotin-ejfv and sacituzumab govitecan-hziy. Adverse events associated with all these drugs are important to consider in rational decision-making.

For example, treatment with enfortumab vedotin may result in peripheral neuropathy and rash. Sacituzumab govitecan treatment is often associated with neutropenia and diarrhea, whereas erdafitinib may cause ocular disturbances requiring monitoring by an ophthalmologist.

“We need better molecular markers to select drug sequencing,” Dr. Petrylak said. “We certainly have markers for erdafitinib with FGFR2/3, but are there better markers to select treatment among erdafitinib, sacituzumab govitecan, and enfortumab vedotin? And how do we use those markers to sequence the next treatment?” 

DISCLOSURE: Dr. Petrylak has received grant or research support from Advanced Accelerator Applications, Agensys, Astellas Pharma, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Eisai, Eli Lilly and Company, Endocyte, Genentech, Gilead Sciences, Innocrin Pharmaceuticals, MedImmune, Medivation, Merck & Co., Mirati Therapeutics, Novartis, Pfizer, Progenics Pharmaceuticals, Replimune Group, and Roche; and has served as a consultant to Advanced Accelerator Applications, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly and Company, Exelixis, Gilead Sciences, Incyte, Ipsen, Janssen, Mirati Therapeutics, Monopteros Therapeutics, Pfizer, Pharmacyclics, Regeneron Pharmaceuticals, Roche, Seagen, and UroGen Pharma.