Dr Petrylak on Sequencing Questions in FGFR2/3-Altered Metastatic Urothelial Cancer

Daniel P. Petrylak, MD, professor, medicine, Medical Oncology and Urology, chief, Genitourinary Oncology, Yale School of Medicine, discusses sequencing treatment selections in patients with FGFR2/3-altered metastatic urothelial cancer.

The optimal treatment sequencing for patients following a diagnosis of FGFR2/3-altered metastatic urothelial cancer remains unclear, Petrylak beings. Sequencing issues will arise more frequently as the use of combination therapies migrates from late treatment stages, such as the adjuvant setting, to earlier treatment stages, such as the neoadjuvant setting, he explains. Checkpoint inhibitors are now also being used as standard-of-care adjuvant therapy post-cystectomy, Petrylak says. With the migration of so many different treatment approaches, investigators are left wondering where to integrate all the newly available treatments, Petrylak emphasizes.

The question of whether to use an FGFR inhibitor after a patient has progressed on systemic chemotherapy or after they have received a subsequent checkpoint inhibitor is currently debated, Petrylak expands. Notably, data from a retrospective trial indicate that patients with FGFR-positive urothelial cancer respond as well to enfortumab vedotin-ejfv (Padcev) as those with FGFR-negative disease, he states, adding these data may guide treatment sequencing strategies in the future.

Response rates with second- and third-line agents appear to be similar to each other, Petrylak continues. However, the toxicity profiles of these agents must be considered. For example, patients receiving FGFR3 inhibitors must be monitored for ocular toxicity, Petrylak emphasizes. Central serous retinopathy is another toxicity associated with FGFR3 inhibitors that ophthalmologists should follow patients for, Petrylak says, and patients’ phosphate levels also need to be monitored. Other adverse effects observed with FGFR inhibitors include skin changes, severe fatigue, neuropathy, hyperglycemia, rash, and interstitial pneumonitis. Those are the toxicities that are the most serious and the most severe, he explains. The choice of FGFR inhibitor includes toxicity management considerations to determine how to best treat patients with metastatic urothelial cancer, Petrylak concludes.