The bigger question is for patients in the first-line setting who may be cisplatin ineligible; is immunotherapy the best treatment for the patient or is chemotherapy still an option? The majority of patients who are not eligible for chemotherapy should be treated with immunotherapy, and then perhaps with chemotherapy after. However, there is clearly a subset of patients who have a very extensive disease burden who are symptomatic and may benefit from chemotherapy first and followed by immunotherapy. That represents about 10% of all patients with bladder cancer.
Will chemotherapy be a mainstay in the treatment of patients with bladder cancer?
Absolutely; I do not think we are ready to give up on chemotherapy. Chemotherapy is still here to stay. It may represent the best option for a proportion of patients. It is still effective and can lead to durable responses in a minority of patients. Certainly, there may be ways of leveraging the effects of chemotherapy along with immunotherapy, perhaps in combination, as well. Certainly, chemotherapy will still be a part of the standard of care for some patients with metastatic bladder cancer.
As we continue to see advances in the field of metastatic bladder cancer, what advice do you have for community oncologists to decipher the new information?
It is tough when there are data coming out almost every other week at another medical meeting. [It is often challenging] to keep up with this information. Participating and continuing medical education activities, trying to attend meetings, and keeping up to date is one of the best ways of doing it. Are we looking at Bacillus Calmette-Guerin (BCG) in combination with systemic therapies? In non-muscle invasive bladder cancer that is intermediate or high risk, patients are often treated with intravesical immunotherapy with BCG. We know that a substantial proportion of these patients, even though they respond to intravesical BCG, will ultimately progress and have refractory/recurrent disease. For those patients, we often treat them with cystectomy, meaning that their bladder must come out. This is after multiple courses of BCG.
Obviously, the challenge is that many of these patients do not want their bladder out. It is a morbid surgery where 60% of patients will have some form of a perioperative complication. This is a pressing need in terms of a novel therapy. There are now trials of systemic immunotherapy agents, such as PD-1 blockade, that is being tested in patients with non-muscle invasive bladder cancer focusing on several subgroups. One of them are patients who had prior BCG and have no other options. They are being treated with PD-1 blockade.
There are also other trials looking at BCG plus PD-1 as primary therapy in patients who have high-risk muscle-invasive disease. We do not have any data yet from any of these trials to know how much PD-1 adds to this disease population. Ultimately, if we see that there are some durable benefits to these patients, then we may envision a future where systemic immunotherapy, such as PD-1 agents, may become standard of care for high-risk non-muscle invasive bladder cancer.
Smith DC, Gajewski T, Hamid O, et al. Epacadostat plus pembrolizumab in patients with advanced urothelial carcinoma: preliminary phase I/II results of ECHO-202/KEYNOTE-037. J Clin Oncol 2017;35 (suppl; abstr 4503).