Changing the Standard of Care in Metastatic Bladder Cancer

Shilpa Gupta, MD: According to the JAVELIN Bladder 100 data that were presented, all the patients benefited regardless of the subgroup, the site of metastasis, or the kind of chemotherapy used. The benefit seems to be more in those with positive PD-L1 than with negative PD-L1; regardless, the benefit exists. I would say that at this point, based on the available evidence, all patients can be offered avelumab maintenance therapy as long as they meet the criteria.

Jeanny Aragon-Ching, MD: There are a lot of factors that we take into consideration when we see a patient who is newly diagnosed with metastatic urothelial cancer: a patient’s age, performance status, kidney function, smoking history, comorbidities—all of them matter. For patient age, I would say it is not necessarily factored into the cisplatin-eligible guidance.

Age is very important, though, as the majority of patients who are diagnosed with bladder cancer are older. This is significant in terms of setting their goals of care. Are they interested in quantity of life versus quality of life or balancing out toxicity? If we’re saying that cisplatin is generally superior to carboplatin, what does that do to their kidney function? Therefore, renal function is a very important factor that we consider in patients who are being treated.

When we talk about chemotherapy, we know that cisplatin causes a predictable decline in their creatinine clearance in renal function. I would say that in the JAVELIN Bladder 100 trial, all patients across the board benefited—whether they got cisplatin or carboplatin—as long as they achieved either CR [complete response], PR [partial response], or stable disease. It’s their response to the treatment, rather than the choice of drug, that dictated whether or not they responded.

Performance status is also an important factor to consider because if it is poor at the very beginning, that is one of the definitions of cisplatin ineligibility or sometimes even platinum ineligibility. They may not be able to receive platinum at all, either cisplatin or carboplatin. Smoking history is a little controversial. Some studies indicate immunotherapy would be better for patients who have a smoking history, whereas others do not support that data.

Comorbidities, of course, do play a role. Whenever we use chemotherapy, any platinum, that ties to renal dysfunction and is closely related to other comorbidities—for instance, in diabetes—we find that a lot of patients may have concomitant problems with their kidney function. All these factors matter in our decision-making for managing patients with metastatic bladder cancer.

I really do think the results of JAVELIN Bladder 100 are revolutionary. Never in the history of bladder cancer have we seen practice-changing responses. This paves the way for more use of maintenance therapy, and for the first time in a long while, we did not have anything other than chemotherapy. Now we have immunotherapy as second-line.

Can we improve on those odds of survival, as well as prolongation of endurability of response by starting them on immunotherapy earlier instead of waiting until progression? I think this is clinically meaningful and changes the standard of care as we know it in metastatic bladder cancer.

Transcript Edited for Clarity