CHICAGO—Immunotherapies for bladder cancer may be making their way into urologic practice, so urologists interested in offering these treatments to patients have some important aspects to consider, Noah M. Hahn, MD, a medical oncologist from Johns Hopkins University School of Medicine in Baltimore, told attendees at the 2018 annual meeting of the Large Urology Group Practice Association.
In a presentation that focused on the urologists' role in immuno-oncology for bladder cancer, Dr Hahn said one consideration is how a urology group feels about offering systemic therapy. An entire practice has to be committed to it. “It's one thing to have a champion who wants to do it … but who's going to take the call on Friday at 4:03 PM when you're out on vacation and your partner is covering? Those things need to be talked about because it's important to have that coverage,” Dr Hahn said.
Another consideration is toxicity management infrastructure. “It's got to be there,” he said. Although immunotherapy is far better tolerated than chemotherapy, adverse events, though rare, still occur. “I think we have to respect the side effects,” Dr Hahn said. “We have to plan for how we're going to help that rare patient that really is pretty sick.”
Immunotherapies such as pembrolizumab and azetolizumab have demonstrated durable complete response (CR) rates in some patients with muscle-invasive and non-muscle invasive bladder cancer, he said. “I'm not sure we can use the word cure yet … “but we're clearly seeing patients that are alive longer than we have ever seen before with these therapies in a group of patients.”
In the past 2 years, 5 immunotherapeutics have been approved for use in the advanced bladder cancer, all targeting PD-1 or PDL-1. In general, monotherapy is associated with CR rates of about 15% across the board, he said. These rates go up when immunotherapies are combined.
Dr Hahn reviewed some of the trials showing the potential of immunotherapies for bladder cancer, starting with the KEYNOTE 045 trial. In that trial, patients with advanced bladder cancer patients who previously received chemotherapy were randomly assigned to receive pembrolizumab or standard therapy. About twice as many patients experience tumor shrinkage (about 20% vs 10%), and those responses were durable, Dr Hahn said. In addition, the trial for the first time demonstrated that an immunotherapy offered a survival advantage over chemotherapy, which Dr Hahn called “a breakthrough, watershed moment for us in the advanced disease setting.”
Dr Hahn also discussed preliminary results from the KEYNOTE-057 trial, a single-arm phase 2 study looking at pembrolizumab therapy for patients with BCG-unresponsive non-muscle invasive bladder cancer. The results, which were presented in October at the European Society for Medical Oncology 2018 congress in Munich, Germany, revealed a 36.5% complete response (CR) rate at 3 months. The median duration of CR was 8.1 months. Of the patients with CR at 3 months, an estimated 85.6% had a response duration of 6 months or more.
“For me as an oncologist, it's been a thrill to see this move into earlier stages of disease,” Dr Hahn said. “I think earlier stage of disease is where we can make our biggest impact because I think that's where the possibility for cure is highest.”
He also talked briefly about a study of atezolizumab (a PDL-1 inhibitor) vs observation as adjuvant treatment in patients with high-risk muscle-invasive bladder cancer who had undergone radical cystectomy. The study population is full accrued, and results are expected in the next 1 or 2 years. “If this shows a benefit for giving immunotherapy following surgery, this would change our practice,” Dr Hahn said.