 Enfortumab vedotin is a very active drug that can give good, long, and durable responses. One priority is to find ways we can make sure we optimize patients’ symptoms so they can continue to be on the drug and benefit from this active agent. We talked about that, the dose reductions, decreasing the frequency, and the supportive medications, like duloxetine or gabapentin, which are all important to make sure the medicine is tolerable. I always tell my patients that the goal of all our therapies is to help them live longer and feel better. If they’re suffering from the toxicity of our medications, that’s going against the quality-of-life goal. That’s very important to all of us and our patients. It’s very important to make sure we’re able to get comfortable with these very active agents and use them in a way that is safe and can preserve quality of life.

I didn’t mention much about cutaneous toxicity, which was also a significant consideration. One other thing we’ve been very successful at here at Stanford [University] with enfortumab vedotin is making sure we have a good team of collaborating physicians who can help us with various toxicities as they come about. We’re eternally grateful to our dermatologic colleagues for helping manage the skin toxicities of enfortumab vedotin and other agents that we use to take care of our patients. With the patient whom I presented, we were fortunate that her dermatology was very responsive in helping co-manage her skin toxicity. Before it even got to a grade 2 toxicity, they were giving her a strong topical steroid and even escalated to a short course of systemic steroids to make sure the toxicity was well managed before it became a bigger problem.

The 3 big take-home points if you’re treating these patients is becoming comfortable with dose reductions and treatment breaks, understanding supportive care medications that can help support patients through the toxicities of these medications, and working with a great team of doctors who can help optimize the management for all of our patients.

Videos

Ali R. Khaki, MD, comments on how to treat patients with advanced bladder cancer based on data demonstrated by the EV-103 study of enfortumab vedotin.

Optimizing Therapy for Patients with Advanced Bladder Cancer

 EV-103 cohort A investigated the use of enfortumab vedotin with pembrolizumab as a combination therapy for patients who are cisplatin ineligible. It’s a single-arm study, but the results are pretty impressive. They had a confirmed objective response rate of 73%, including a 17.8% complete response rate and a 57% response rate in those with liver metastases. The duration of response was over 2 years, at 25.6 months. These are very impressive numbers, but this was a very small trial. I’m not sure if this has changed my practice. The sample size was small. It’s an uncontrolled trial. We need more data before I recommend adopting this as the new frontline therapy for patients who are cisplatin ineligible.

My practice for people who are cisplatin ineligible, is to adopt the JAVELIN Bladder 100 model of carboplatin combination chemotherapy followed by maintenance avelumab immunotherapy. We have a higher level of evidence to support this practice. That’s what my standard of care is. In patients who are platinum ineligible, who aren’t even candidates for carboplatin chemotherapy, my typical practice is to use pembrolizumab monotherapy. Especially if someone has symptomatic disease or is in great need of an urgent response because of the pace of their disease, that might be a population where I reach for this combination despite pretty premature data, because of the impressive results: the response rate over 70% and durable response of over 2 years.

With the majority of patients I treat, even frail patients, we’re often able to get them through at least 4 cycles of combination carboplatin chemotherapy. That’s still my preferred approach for first-line therapy when possible. There are some patients who, given their frailty or comorbidities, may not be platinum chemotherapy candidates. That’s when my typical practice has been immune checkpoint inhibitor monotherapy. But in patients with very symptomatic or aggressive disease, with liver or bone metastasis—particular clinical features that might suggest more metastatic biology—those are whom I might consider for this combination of EV [enfortumab vedotin] plus pembrolizumab as initial therapy.

The big goal is making sure patients who are eligible get all lines of therapy they’re able to get. With frail patients, that might be a setting, especially if you think you have only 1 shot at a treatment, to make sure you give people all active agents. If you can’t get platinum chemotherapy, the 2 most active agents are probably immune checkpoint inhibitor and enfortumab vedotin.

Ali R. Khaki, MD, describes the impact of the EV-103 study of enfortumab vedotin in advanced bladder cancer.

Ali R. Khaki, MD

Articles

Optimizing Therapy for Patients with Advanced Bladder Cancer

Study EV-103 in Advanced Bladder Cancer