Novel IL-2 Based Combinations for Bladder Cancer - Episode 1

Overview of Urothelial Cancer

May 8, 2019

Arlene O. Siefker-Radtke, MD:Urothelial cancer, which is more commonly referred to as bladder cancer, typically occurs in approximately 60,000 to 80,000 new patients every year. Despite that high incidence rate, there are typically only 15,000 to 20,000 deaths. So 1 of the big difficulties in the treatment of bladder cancer is determining how many of our bladder patients diagnosed with a superficial bladder cancer will transform into that aggressive bladder tumor that has a chance of killing them with this disease.

When we look at the treatment options for bladder cancer, the large majority are treated by our urologic oncology colleagues, where they get transurethral resections and even intravesical therapy providing control of their tumor and the ability to maintain their bladder. However, there’s still a definite group of patients who develop invasive disease, a disease that’s characterized by its aggressive nature and ability to begin spreading to other locations. Those are the patients who typically need neoadjuvant chemotherapy followed by surgery. The difficulty in treating these patients is that they’re frequently elderly and frail. The average age of the bladder cancer patient is typically in the mid-70s, and they often have comorbid medical conditions induced by smoking and other medical conditions that can impact their ability to tolerate a curative therapy.

Once they enter into the stage of metastatic bladder cancer, unfortunately the prognosis is quite poor. There are few long-term survivors from this stage of disease, and the typical goal has been to buy patients as much time as we possibly can, mostly through the use of systemic chemotherapy followed by immunotherapy, and the recent approval of an FGFR3 inhibitor called erdafitinib. Despite that, long-term survival remains poor, and there are clearly several unmet needs in the treatment of our bladder cancer patients.

When we look at 1 of the unmet needs, a question is, what should we do for the patient who cannot tolerate cisplatin? A lot of bladder cancer patients have poor kidney function, either due to their comorbid medical conditions—many induced by smoking—or a tumor obstructing their ureters and impacting their kidney function. In fact, it’s estimated that nearly 50%, or more, of patients diagnosed with urothelial cancer who need systemic chemotherapy are not candidates for a cisplatin-based regimen.

That is why everyone was so excited by the recent approval of immune checkpoint inhibitors for the treatment of bladder cancer. They were approved as a second-line therapy in patients with metastatic disease, but also in the frontline setting, which was a definite improvement when you consider the toxicity typically observed with a cisplatin-based chemotherapy regimen. More recently, the FDA provided guidance based on trials. We have not yet seen the clinical data, but based on what they observed, there appeared to be inferior outcomes with the use of an immune checkpoint inhibitor in patients with PD-L1 [programmed death-ligand 1]—low tumors.

As a result, the FDA modified its criteria indicating that frontline immune checkpoint inhibition should be reserved for patients with high—PD-L1 expression.

Transcript edited for clarity.