How Many Lines of Therapy Are Patients Receiving for Urothelial Carcinoma?


A brief review of sequencing patterns in urothelial carcinoma and the typical number of lines of therapy a patient may receive.


Shilpa Gupta, MD: A few years ago, we saw these real-world practice patterns where the majority of patients were not being referred for second-line or third-line therapies and very few got frontline therapies despite approval of all these novel agents. In your practice, how many patients are being offered frontline, second-line, or third-line and beyond therapies? Let’s start with you, Petros.

Petros Grivas, MD, PhD: You raise a great question, because there have been publications by Dr Umang Swami, MD, MS, at the University of Utah Huntsman Cancer Institute in Salt Lake City; Dr Jeffrey A. Morgan, MD, at the Dana-Farber Cancer Institute in Boston, Massachusetts; and others looking at the proportion of patients who undergo systemic therapy across different lines of therapy in metastatic urothelial cancer. Conventionally, these proportions have been of patients who never started therapy; neoadjuvant therapy was surprisingly high. I remember publications that show only about half of patients got first-line therapy, 1 out of 5 patients made it to second-line therapy, and less than 10% to third-line therapy.

These are data from 2018 that Dr Swami, Dr Neeraj Agarwal, MD, at the University of Utah Huntsman Cancer Institute, myself, and others published. And our hope has been that in the past 5 to 6 years we’re seeing more and more patients receiving treatment and staying on the train of therapy. Of course, this hopefully translates into longer survival, better outcomes, and better quality of life for patients. I think this has had to do with the absence of effective life and safe life-proven therapies in the past. But in the past 6 years, with the advent of immune checkpoint inhibitors, antibody-drug conjugates, and defeating the target therapies, I think we have many more options for our patients. Hopefully, the proportion of patients who never get any treatment is getting lower and lower and the proportion of those who get treatment is getting higher. Obviously, we now have more clinical trials, and of course, we’re working to address the major issue of health care disparities and access to health care, which is another big challenge globally.

Shilpa Gupta, MD: Mamta, how about you?

Mamta Parikh, MD, MS: I have a very similar experience to Petros, but one of the things that’s underappreciated in managing patients with metastatic disease is that sometimes local symptoms can really cause issues in terms of trying to get patients through therapy. So it is important even with metastatic disease to involve urology in our treatment patterns. But with newer agents and better treatments available, we’re able to get more patients through to second- and third-line therapy. The patients whom I’ve seen haven’t been able to get through first-line therapy, though often it’s related to local issues.

Shilpa Gupta, MD: Andrea, in your practice, I’m sure you see a lot of referrals. So you must be seeing a lot of late-line therapies. Are the patients robust enough to get those?

Andrea B. Apolo, MD: I do, because we’re a tertiary referral center and a research hospital and we are now seeing patients after the third- or fourth-line therapy, which is terrific. It used to be we would get patients after cisplatin-based chemotherapy, after first-line therapy, and the options that followed that were not as exciting with Taxol-based single-agent chemotherapy. So now we have a lot more options.

The community oncologists are using checkpoint inhibitors; they’re using antibody-drug conjugates. So we are getting patients at later lines of therapy for our clinical trials, which is great because it’s nice to have these options, and it’s nice that they’re being used and that the community oncologists feel comfortable using these treatments for our patients.

Shilpa Gupta, MD: We’ve come a long way in the past few years when we had nothing after chemotherapy.

Transcript edited for clarity.

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