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Adoption of Avelumab for First-Line Maintenance Therapy of Urothelial Cancer in US

February 19, 2021


Petros Grivas, MD, PhD, University of Washington, Fred Hutchinson Cancer Center, Seattle Cancer Care Alliance, discusses results from a qualitative interview study evaluating the adoption of avelumab first-line maintenance therapy as standard of care in academic and community oncology practices in the United States.

These results were presented at the virtual 2021 ASCO Genitourinary Cancers Symposium.


Hello, I'm Petros Grivas. I'm a medical oncologist at Seattle Cancer Care Alliance. I'm an associate professor at University of Washington and the clinical director of the Genitourinary Cancers Program here. I'm also an associate member of the Fred Hutchinson Cancer Research Center.

I'm very excited about all the data we saw at ASCO GU 2021. We saw a lot of amazing datasets, and I would like to focus our discussion today on a poster we had the opportunity to present focusing on real‑world evidenceI would call it a pragmatic studyevaluating patterns of care, treatment patterns, especially in the front‑line setting of advanced urothelial cancer.

This work that was presented at ASCO GU 2021 focused on interviews with cancer specialists in the United States, as I mentioned before, to better understand the different treatment patterns and options in the front‑line setting of advanced urothelial carcinoma.

For background for folks who are not oncologists here in the audience, urothelial cancer can affect the entire urinary tract. Bladder is the most common organ of origin for urothelial cancer. However, urothelial cancer can arise from the internal part of the kidney, kidney‑pelvis, or the ureters or the urethra. 

As I mentioned, by far the most common origin of urothelial cancer is bladder. Within the bladder organ, the most common histologic type of bladder cancer is urothelial cancer. When it is spread, this cancer is called metastatic, when it goes to different organs, lymph nodes and other multi‑site organs. 

Traditionally and conventionally over the last 30 years, cytotoxic chemotherapy, specifically platinum‑based chemotherapy, has been the treatment of choice in this front‑line setting, front‑line meaning patients who were not treated before for metastatic urothelial cancer. 

They have this diagnosis of metastatic urothelial cancer, and they start treatment. Most of them get platinum‑based chemotherapy consisting of either gemcitabine‑cisplatin (we call it gem‑cis) or gemcitabine‑carboplatin (we call it gem‑carbo). 

There have been a lot of datasets and clinical trials in this front‑line setting recently. To name three trials that are relevant to our discussion, the IMvigor130, the KEYNOTE‑361, and the JAVELIN Bladder 100 trial. The reason I mention these three trials is because they provide context for this poster.

Two of them, the IMvigor130 and the KEYNOTE‑361, evaluated the question whether concurrent, at the same time, combination of chemotherapy and immunotherapy can improve outcomes in the front‑line setting of this disease. 

Specifically, IMvigor130 evaluated chemotherapy plus atezolizumab vs chemotherapy placebo. The KEYNOTE‑361 evaluated chemotherapy pembrolizumab vs chemotherapy. 

Both of those trials were presented and showed that the addition of immune checkpoint inhibition, the atezolizumab IMvigor130 and the pembrolizumab in KEYNOTE‑361, did not significantly prolong overall survival. 

There was a lot of discussion about these two trials. The consensus among the scientific community is that, based on this lack of overall survival benefit, the practice did not change. Notably, in the IMvigor130, there was, I would say, modest progression‑free survival benefit with the chemo‑atezo versus chemotherapy-placebo. However, this was not translating into a practice change.

Based on that, the concurrent chemotherapy‑immunotherapy combination did not go forward, so far, but we have longer follow‑up to see from the IMvigor130. 

At the same time, we saw results from the JAVELIN Bladder 100 trial that treats maintenance avelumab immunotherapy after response or stable disease, after induction with platinum‑based chemotherapy, prolongs overall survival. 

This sequential approach with avelumab given after disease control, response or stable disease to chemotherapy, prolonged overall survival significantly in the JAVELIN Bladder 100 trial when it was published in the New England Journal of Medicine, September 2020, and changed the guidelines in the US and changed guidelines in Europe, ESMO Guidelines. 

Now there are many approvals by the FDA, the EMA, and many other countries. The standard of care right now in the front‑line setting, based on these guidelines and the JAVELIN Bladder 100 trial, is platinum‑based chemotherapy, gem‑cis or gem‑carbo, for example. In those who achieve response or stable disease, they go ahead and do avelumab switch maintenance.

In this particular poster we showed, we tried to evaluate what was the adoption of this standard of care in the community oncology practices. There were phone interviews. 

Oncology attendings and nurses who had experience in treating this disease, and cancer in general, were asked whether they implemented the standard care which is based on the JAVELIN Bladder 100 trial, treatment option 1, or they give concurrent chemo‑immunotherapy, and what were the reasons for this decision. 

About half of the oncology physicians and about a third of oncology nurses had over 15 years of experience in treating cancer. 

Overall, when they were asked about these 2 options, 67% of physicians and 71% of the nurses, so the majority, opted for the standard of care, the treatment option 1, which is induction platinum‑based chemotherapy followed by immunotherapy, a switch maintenance approach, in those with response or stable disease.

The majority of those pretty much implement the standard of care. There was discussion about the reasons why some specialists opted to use only immunotherapy alone in the front‑line setting. These were mainly for patients who were frail, elderly, and could not tolerate platinum‑based chemotherapy. 

There's some context for this. We published data from the KEYNOTE‑052 trial in the European Urology Oncology a few months ago showing that pembrolizumab seems to benefit those patients who cannot tolerate platinum‑based chemotherapy in the front‑line space, this so‑called platinum, cis and carbo, unfit patients. 

Overall, this gives some light about the treatment patterns in the front‑line space. Obviously, limitations include the observational nature, small sample size, and, of course, the data we present are a summary of the methods. 

It's important to point out that even if the FDA approved avelumab switch maintenance on end of June of 2020, there is a quick adoption of this treatment paradigm in the community oncology setting. Cancer specialists felt that the most important factors when making treatment decisions were overall survival, people to live longer, and also to avoid side effects, try to avoid adverse events if possible.

Overall, toxicity and cost are also relevant factors, as we know, in clinical practice. Overall, it's important to keep doing these studies, keep generating this real‑world evidence to understand factors that affect treatment patterns, and do a little bit more work with cost‑effectiveness in the real‑world setting.

On behalf of the co‑investigators and the research team, I would like to thank you for your attention to our poster. Looking forward for more studies in the future.

Grivas P, Huber C, Pawar V. Approaches to immune checkpoint inhibitor (ICI) maintenance therapy in metastatic urothelial cancer (mUC): A qualitative analysis of oncology providers in the United States. Presented at: the virtual 2021 ASCO Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 407.

Dr Grivas reports institutional research funding from Bavarian Nordic; Bristol-Myers Squibb; Clovis Oncology; Debiopharm; Immunomedics; Pfizer; Merck; QED Therapeutics; GlaxoSmithKline; Mirati Therapeutics; and Kure It Cancer Research and consultation payment from AstraZeneca; Dyania Health; EMD Serono; Immunomedics; Infinity Pharmaceuticals; Janssen; Merck; Mirati Therapeutics; Genentech; Pfizer; and Seattle Genetics.

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