Dr Park on the Sequencing of Treatment Options in Metastatic Urothelial Cancer

Chandler H. Park, MD, FACP, medical oncologist, Norton Healthcare, discusses the implications of evaluating sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) in cohort 3 of the phase 2 TROPHY-U-01 trial (NCT03547973) in patients with metastatic urothelial carcinoma who have progressed following platinum-based chemotherapy.

Treatment decisions are challenging for patients with progressive urothelial cancer, and questions remain regarding the sequencing of available therapies, Park begins. A wealth of new bladder cancer data has emerged, prompting oncologists to consider how these data integrate with existing information, he states. Among the significant studies unveiled at the 2023 ESMO Congress, the phase 3 EV-302 trial (NCT04223856) stands out, establishing first-line enfortumab vedotin-ejfv (Padcev) plus pembrolizumab as a new standard of care, Park explains. Factors such as response rate, duration of response, and durability of response influence the decision to administer this regimen upfront to many patients, he adds.

Another noteworthy study, the phase 3 CheckMate 901 trial (NCT03036098), introduced cisplatin plus gemcitabine and nivolumab (Opdivo) as another effective treatment option for patients with advanced urothelial cancer, Park expands. Now, oncologists are confronted with the phase 3 JAVELIN Bladder 100 trial (NCT02603432), offering various chemotherapy combinations alongside maintenance avelumab (Bavencio), he elucidates. These emerging studies prompt consideration for how the TROPHY-U-trial regimen aligns with existing frontline treatment options, Park reports.

The absence of phase 3 prospective studies of enfortumab vedotin plus pembrolizumab in urothelial cancer raises questions about the continued benefit of pembrolizumab, he says. Although retrospective analyses have evaluated the use of immunotherapy in later lines of treatment, there's insufficient evidence to support this approach following enfortumab vedotin and pembrolizumab, Park emphasizes.

Patients receiving cisplatin plus gemcitabine with nivolumab may not benefit from enfortumab vedotin plus pembrolizumab, Park continues. However, if patients receiving carboplatin or cisplatin, gemcitabine, and maintenance avelumab develop severe peripheral neuropathy or uncontrolled diabetes, sacituzumab govitecan plus pembrolizumab becomes a viable treatment option, according to Park, as TROPHY-U-01 evaluated patients within these demographics, Park concludes.