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First-Line Treatment Approaches for Metastatic Urothelial Cancer in the US

May 04, 2021

Petros Grivas, MD, PhD, University of Washington, Seattle Cancer Care Alliance, discusses results from a qualitative study exploring decision-making processes regarding first-line treatment choices, testing practices, and treatment eligibility determinants for patients with metastatic urothelial cancer.

These results were presented at the 2021 virtual National Comprehensive Cancer Network (NCCN) Annual Conference.


Hello. I'm Petros Grivas. I'm a medical oncologist at Seattle Cancer Care Alliance, associate professor at the University of Washington at Fred Hutchinson Cancer Research Center.

I'm very excited because we have done some work with a great team related to a qualitative analysis of oncology providers in the United States regarding the strategies, approaches to the use of checkpoint inhibitors in the front‑line setting of advanced urothelial cancer.

This work was done with the aim to understand the reasons, the factors that influence, impact the clinical decision‑making in the first‑line setting of advanced urothelial cancer and also to identify barriers for why people may not be able to adopt the standard of care.

To preface my presentation, I would like to point out the clinical context in terms of data. I want to remind the audience of the practice‑changing results of the JAVELIN Bladder 100 trial that utilized avelumab plus best supportive care versus best supportive care alone in a randomized fashion in patients with response or stable disease to induction‑based chemotherapy.

Avelumab plus best supportive care prolonged overall survival and progression‑free survival in this switch maintenance setting resulting in a new standard of care, level one evidence of switch maintenance avelumab after response or stable disease chemotherapy, and as I mentioned, changed the NCCN guidelines, ESMO guidelines, and received FDA approval in the summer of 2020.

At the same time, we have a number of clinical trials in the front‑line setting with concurrent chemotherapy plus immunotherapy utilization, like the KEYNOTE‑361 or the IMvigor‑130, but those trials have not changed the standard of care because they have not shown significant overall survival benefit with a concurrent chemotherapy/immunotherapy combination.

Because of this factor, in the absence of significant overall survival benefit, right now, we are not using concurrent chemotherapy, immunotherapy in advanced urothelial cancer. We're using the switch maintenance approach with switch maintenance avelumab after response or stable disease to chemotherapy.

We wanted to evaluate the practice patterns of oncology providers and oncology nurses. Specifically, we conducted interviews on 18 oncology providers and 18 oncology nurses who have experience treating patients with advanced urothelial cancer. We used a semi‑structured discussion guide to explore this decision‑making process about the treatment patterns in the first‑line setting.

We asked specifically whether the providers and the nurses would use platinum‑based chemotherapy followed by switch maintenance immunotherapy as per the standard of care and level one evidence, or whether they would use concurrent chemotherapy and immunotherapy, and the reasons behind this particular practice.

Interviews were audio‑recorded and transcribed verbatim, and the transcripts were coded and analyzed using the constant comparative method to identify the key determinants in clinical considerations related to decision‑making in the front‑line setting.

Demographics and clinical screening responses of the study participants were analyzed in terms of summary statistics in a descriptive manner. All data were collected in a double‑blinded manner, and the study received an exemption from the Advarra IRB.

As I mentioned before, 18 US‑based medical oncologists and 18 oncology nurses participated in the study. Providers commonly administered cisplatin or carboplatin‑based therapy as first‑line therapy.

The participants used the so‑called Galsky criteria to evaluate whether a patient is fit enough to receive cisplatin. The Galsky criteria, to remind the audience, include performance status, kidney function, cardiac function, neuropathy, hearing loss. Those were some of the criteria we use in clinical practice.

Patients who were not considered eligible, patients who were not considered fit for platinum‑based chemotherapy, especially frail patients with medical comorbidities, received checkpoint inhibitor as single‑agent monotherapy. The FDA allows the use of pembrolizumab or atezolizumab in these patients who cannot tolerate any cisplatin or carboplatin.

The oncologists recommended four, five, or six cycles of platinum‑based chemotherapy in the front‑line setting of advanced urothelial cancer. Both oncologists and nurses groups mentioned the response to chemotherapy as being assessed after two to four cycles of platinum‑based chemotherapy.

Most participants, about 67 percent of oncologists and 71 percent of nurses, preferred the standard of care, which is platinum‑based chemotherapy followed by switch maintenance immunotherapy in patients who had several response or stable disease.

The providers cited factors like toxicity and cost, as well as efficacy, overall survival, as key determining factors of how they make clinical decisions in the front‑line setting. Providers universally did not recommend a treatment break between chemotherapy and checkpoint inhibitor in the maintenance setting because of concerns of disease progression.

We described the demographics of the participants, and also, we provided the schematic of the switch maintenance immunotherapy, which is now the standard of care.

Overall, we have some very interesting descriptive analysis and narrative of the reasons why the standard of care may or not be incorporated in the first‑line setting as well as factors, decision‑making points, that providers take into account, and became apparent that, again, efficacy, measured by overall survival, as well as toxicity side effects and cost are relevant factors in this decision‑making.

The study had limitations, a potential selection bias in regard to who was the person who answered the survey. There may be some selection or confounding bias there in terms of who answered the particular survey and who did not.

Furthermore, the findings represent the experience and perspective of a small sample size of only 36 individuals, 18 oncologists, 18 nurses, who may not necessarily be representative of the entire spectrum of the practicing oncologists and nurses in the US.

There could be a potential bias due to recollection and, as I said, recall‑time bias. However, overall, I would say the study is one of the novel studies in this field trying to identify real‑world practice patterns, assess which factors are relevant to oncology providers and nurses in making decisions in the front‑line setting, as well as barriers for the adoption of the standard of care therapy in advanced urothelial cancer with level‑one evidence as we have now the switch maintenance avelumab after response or stable disease to platinum‑based chemotherapy.

I would like to thank the team for great work in this particular study. Thank you for the invitation to present the summary of our results. We're working on a manuscript in order to be able to disseminate the data and further stimulate discussion in the community. Hopefully, in the future, similar studies to this and maybe bigger studies can further evaluate these important questions. Thank you so much for your attention. Stay safe.

Grivas P, Roach M, Pawar V, et al. A Qualitative Study Describing Oncology Practitioners' Approaches to First-Line (1L) Treatment of Metastatic Urothelial Cancer (mUC) in the United States. Presented at: the NCCN 2021 Virtual Annual Conference; March 18-20, 2021. Abstract BPI21-004.

Dr Grivas reports consulting payment from Merck, Bristol-Myers Squibb, AstraZeneca, Clovis Oncology, EMD Serono, Seattle Genetics, Foundation Medicine, Pfizer, Janssen, Genzyme, Mirati Therapeutics, Exelixis, Roche, GlaxoSmithKline, Genentech, Immunomedics, Dyania Health, Infinity Pharmaceuticals, QED Therapeutics, and 4D Pharma PLC; and research funding from Pfizer, Clovis Oncology, Bavarian Nordic, Immunomedics, Bristol-Myers Squibb, Debiopharm Group, Merck, QED Therapeutics, Kure It Cancer Research, GlaxoSmithKline, and Mirati Therapeutics.

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