Although bladder cancer is among the most chemosensitive of the solid tumors, and a large proportion of patients will achieve objective tumor regressions on first-line therapy with conventional chemotherapeutic regimens, response durations are relatively short and outcomes with existing second-line therapies are modest at best, explained Matthew D. Galsky, MD, Director, Genitourinary Medical Oncology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York.

“Randomized clinical trials in both the first- and second-line metastatic settings have demonstrated that a ceiling in efficacy has likely been reached with conventional cytotoxic drugs [in bladder cancer], particularly in unselected populations, and novel approaches are urgently needed,” Dr. Galsky continued.

Patient Selection

Commenting on Dr. Hahn’s presentation, Dr. Galsky said that each of the approaches he described is likely to be most successful if clinical and/or pathologic characteristics can be used to select patients who are most likely to derive benefit.

“In this regard, a few of the strategies outlined by Dr. Hahn that have reached clinical testing are particularly intriguing,” Dr. Galsky said. “The COXEN approach, which utilizes the publicly available gene-expression profiling data and drug sensitivity data from the NCI-60 cell line panel as a ‘Rosetta Stone’ to predict chemosensitivity of gene-expression–profiled bladder cancer samples using a computational algorithm, may ultimately allow ‘smarter’ use of our existing armamentarium of cytotoxics. The DN24-02 active cellular immune therapy may one day provide a noncytotoxic option for adjuvant therapy for patients with HER2-expressing locally advanced bladder cancers. Finally, drugs targeting FGFR3, in patients with tumors harboring FGFR3 mutations, may provide proof of concept for the elusive molecular ‘Achilles heel’ in advanced bladder cancer,” he elaborated. 

However, he added that none of these approaches will advance treatment of bladder cancer without a concerted commitment by the medical community and patients to complete ongoing clinical trials. “This is historically among the largest barriers to improving outcomes in this disease,” Dr. Galsky stated. ■

Disclosure: Dr. Galsky reported no potential conflicts of interest.