Dr. Grivas discusses real-world study of frontline avelumab maintenance in urothelial carcinoma


Avelumab is approved by the FDA as a maintenance therapy for patients with locally advanced/metastatic urothelial carcinoma that has not progressed with first-line, platinum-based chemotherapy.

In an interview at the 2023 ASCO Genitourinary (GU) Cancers Symposium, lead author Petros Grivas, MD, PhD, discussed his abstract on the PATRIOT-II real-world retrospective study of avelumab as first-line maintenance in patients with locally advanced/metastatic urothelial carcinoma.1

“Obviously, this is a retrospective study, but I think it will give us some interesting data of how the implementation of avelumab maintenance looks like in the real-world practice,” said Grivas.

“Obviously, this is a retrospective study, but I think it will give us some interesting data of how the implementation of avelumab maintenance looks like in real-world practice,” said Grivas.

The FDA approved avelumab in 2020 as maintenance therapy for patients with locally advanced/metastatic urothelial carcinoma that has not progressed with first-line, platinum-based chemotherapy, based on findings from the phase 3 JAVELIN Bladder 100 trial (NCT02603432).2

Grivas is a physician at the Seattle Cancer Care Alliance, an associate professor in the Division of Medical Oncology, University of Washington (UW) School of Medicine, clinical director of the Genitourinary Cancers Program, UW Medicine, and an associate professor in the Clinical Research Division, Fred Hutchinson Cancer Research Center, in Seattle, Washington.

Please discuss the purpose of the retrospective PATRIOT-II study.

I will start by saying that we have made huge progress in the field of metastatic urothelial cancer with the JAVELIN Bladder 100 trial (NCT02603432) showing that avelumab switch maintenance immunotherapy after response of stable disease to platinum-based chemotherapy prolongs overall survival and progression-free survival as a standard of care. In those patients, we also want to do long term follow up of that study and we had Dr. Sridhar present that data at the 2023 ASCO GU Symposium. There are also some very interesting manuscripts that are coming out soon looking at longer-term follow up, as well as the analysis of different subsets from the JAVELIN Bladder 100 trial.

In addition to that, we want to also corroborate the findings by real-world data. So in an effort to describe real-world evidence of what is happening in clinical practice, we designed the PATRIOT-II study. It was additional designed with a prospective and retrospective component. Because of accrual and budget limitations, however, we have to focus on the retrospective components.

So PATRIOT-II is a retrospective observational US-based multi-center real-world study of avelumab first-line switch maintenance therapy in patients with advanced urothelial carcinoma. And particularly at ASCO GU 2023, we had the first analysis from the study being presented. It was a subset of data in 160 patients and we focused particularly on treatment patterns with regards to the induction chemotherapy phase, until patients started avelumab maintenance therapy.

Could you expand a little bit on the design and methodology of the study?

Absolutely. So initially, as I mentioned, we tried to make it perspective and retrospective, and also collect quality of life and patient-reported outcomes data, but as I mentioned, we had to restrict it to a retrospective chart review. So we collected data from patients who received chemotherapy, and then went on to avelumab switch maintenance. Patients were accrued in 37 geographically dispersed oncology practices, both community practices and academic centers within the US. And the inclusion criteria included patients who started avelumab switch maintenance therapy in the frontline setting, and that was one of the main inclusion criteria that we used. And as I mentioned, we had collected data even before avelumab started, and that was the focus of the poster we had at ASCO GU—looking at the treatment patterns, utilization of chemotherapy, response, outcomes, toxicity with induction chemotherapy, and, of course, baseline characteristics and features of those patients will use descriptive statistics to pursue this analysis.

And so moving into some of those baseline characteristics of the patient population, what disease status and baseline characteristics were observed at platinum-based chemotherapy initiation?

So we had 160 patients enrolled and about three-quarters were men, and the median age was about 70, which is what you expect in this patient population. These are patients with locally advanced unresectable or metastatic urothelial cancer. So these are patients treated with not curative intent. Obviously, we want to be sensitive about healthcare disparities and we tried to include data from patients across different racial and ethnic groups and about three-quarters of the patients were white, and we had about 10% non-Hispanic patients. Of course, it's very important to include those populations in our studies across the border. Two-thirds of the patients were either current or former smokers.

And about half of the patients were tested for PD-L1 via various different assays. And from those who were tested for PD-L1, about 57% were PD-L1 positive. Obviously in clinical practice we are not using PDL-1, at least in my practice we do not find this useful because patients who are fit to get chemotherapy, they get platinum-based chemotherapy of cisplatin if they're fit enough or carboplatin if they are not fit for cisplatin. So, personally I do not find PD-L1testing useful; however, we want to collect the data in this particular patient population.

The ECOG performance status of patients was 0 to 1 in about three-quarters of patients. We had a significant proportion of patients with upper tract disease, although the majority had lower tract disease.

Please discuss some of the key findings.

We actually looked at which chemotherapy regimen the patient received. In terms of the chemotherapy regimens patients received, as I mentioned, either cisplatin-based chemotherapy or carboplatin. About two-thirds of the patients had received cisplatin and about one-third carboplatin.Patients received a median of 4 chemotherapy cycles with a range between 3 and 6. And the median duration of chemotherapy was 13 weeks.

Overall, 13% of patients had a complete response, 68% had a partial response, and the remaining patients had stable disease, with very few patients not having data available for best response. Obviously, this is a very selected patient population who wound up getting avelumab maintenance and so we excluded patients with progression to chemotherapy.

The median time to first imaging from starting of chemotherapy was about 10 weeks, 2 and a half months, which is usually consistent with what you see in clinical practice. About 14% were hospitalized while receiving chemotherapy, and 16% went to the emergency department. Again, these are the numbers that you would expect probably for a general population with other medical comorbidities. And some of them will compromise performance status in the frontline setting of advanced cancer, receiving induction-based chemotherapy.

Patients after the completion of chemotherapy, proceeded to avelumab first-line maintenance after a median of 4 weeks, and there was a range between 3 and 6 weeks. This was the interval between end of chemotherapy and start of avelumab maintenance. Avelumab was administered the standard dose of 800 mg every 2 weeks intravenously in the vast majority of patients.

Moving forward, what future analyses are planned for this research or inspired by this research?

So in the future, we're going to focus more on the actual outcomes with avelumab switch maintenance immunotherapy. We're going to look at progression-free survival (PFS), overall survival (OS), secondarily to response rates. In that context, obviously, PFS and OS are more meaningful in the context of maintenance therapy. Obviously, this is a retrospective study, but I think it will give us some interesting data of how the implementation of avelumab maintenance looks like in the real-world practice.

We're also going to try to evaluate the toxicity and safety profile of maintenance avelumab. We're excited about the conduction and, of course, the longer follow up of this study. And I think with longer follow-up, we're going to capture real-world data about avelumab maintenance.


1. Grivas P, Barata PC, Moon H, et al. Baseline characteristics from a retrospective, observational, US-based, multicenter, real-world (RW) study of avelumab first-line maintenance (1LM) in locally advanced/metastatic urothelial carcinoma (la/mUC) (PATRIOT-II). J Clin Oncol. 2023;41(suppl 6):465. doi:10.1200/JCO.2023.41.6_suppl.465

2. FDA approves Bavencio as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma. News release. Pfizer. June 30, 2020. Accessed February 20, 2023. https://www.pfizer.com/news/press-release/press-release-detail/fda-approves-bavencio-first-line-maintenance-treatment

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