The Expanding Treatment Paradigm for Urothelial Carcinoma - Episode 2

Treatment Options for Localized Bladder Cancer

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A brief review of both neoadjuvant and adjuvant treatment options available to patients with localized bladder cancer.

Transcript:
Petros Grivas, MD, PhD:
Thank you so much, Srikala. And I will follow up with Cora here. We have so much going on in localized bladder cancer. You have done so much work in the field yourself. Can you give us a little bit of a window of time here, how do we treat localized bladder cancer?

Cora Sternberg, MD, FACP: I’m going to talk about locally advanced bladder cancer, muscle-infiltrating bladder cancer. For the majority of patients, for many years, we’ve given neoadjuvant chemotherapy, which means upfront chemotherapy, before going on to cystectomy. This usually contains cisplatin combination chemotherapy. And we’ve done a meta-analysis as far back as 2005 in many, many patients showing that that will improve survival by at least 5%. The analysis done on adjuvant therapy was done on very small numbers of patients, and we really had no clear indication toward adjuvant therapy. But most recently there have been more adjuvant therapy studies, randomized studies giving chemotherapy to those patients who didn’t receive neoadjuvant chemotherapy.

One of the largest was the EORTC [European Organisation for Research and Treatment of Cancer] study (NCT00028756) in which I participated. But doing a large meta-analysis together with the MRC [Media Rating Council], we recently published in the journal ... works on 10 different randomized studies. And we saw that giving adjuvant chemotherapy does improve survival just as well as neoadjuvant chemotherapy. And at this ESMO congress, we also have an interesting poster looking at surrogate end points for disease-free survival and on distant metastasis-free survival to try to look for surrogate end points for adjuvant therapy.

Many of the patients after cystectomy do get adjuvant therapy, but it takes a long time for us to understand the studies. Many studies with adjuvant therapy and other tumors as well are looking for surrogate end points so we don’t have to always wait for overall survival. But what we did see in this study that was just published recently in ... was similar results to the neoadjuvant data. We had individual patient data from the 10 randomized studies with over 1,100 patients, and we saw here again a 6% absolute difference in overall survival, which became a 9% difference improvement in overall survival when they looked at confounding factors such as age, sex, stage, and other factors like that. So if patients didn’t get neoadjuvant therapy, there’s always adjuvant therapy.

We also have new data recently on immunotherapy for patients who have had primarily neoadjuvant chemotherapy or who were ineligible for some reason to get neoadjuvant chemotherapy. And most are published in the New England Journal [of Medicine]. One not that long ago showed that 1 year of adjuvant nivolumab in patients who still had muscle-infiltrating disease or node-positive disease would improve disease-free survival. We don’t have the overall survival results yet. It takes a long time, which is why we’re looking for surrogate end points. There was another study, the atezolizumab study, that was not a positive study. And we’re still waiting for the results of the AMBASSADOR study (NCT03244384), which is with pembrolizumab in terms of immunotherapy.

Petros Grivas, MD, PhD: Wonderful overview, Cora. In a short amount of time, you covered the totality of the data. And congratulations on the work and your poster here.

Cora Sternberg, MD, FACP: Thank you.

Petros Grivas, MD, PhD: And for the audience, I think it’s a very interesting point that if someone is fit for cisplatin and they never receive neoadjuvant chemotherapy, but they have a high risk of recurrence, pathologic T3 or T4 node-positive disease, they’re chemo naive, you would offer cisplatin-based chemotherapy.

Cora Sternberg, MD, FACP: Absolutely.

Petros Grivas, MD, PhD: Good to know. In the CheckMate 274 trial (NCT02632409) data, we show the data before publishing. So we have possibly biomarker data at ESMO Congress 2022. So interesting to see that data.

Transcript edited for clarity.