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Treatment Patterns After PD1/L1 Inhibitor Discontinuation in Advanced Urothelial Carcinoma

March 19, 2021


Alicia Morgans, MD, MPH, Northwestern University Feinberg School of Medicine, Chicago, IL, discusses results from study which examined treatment patterns among patients with metastatic urothelial carcinoma previously treated with PD-1/L1 inhibitor therapy.

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


Hi, my name is Alicia Morgans, and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University in Chicago in the United States. I'm so excited to talk with you today about a recently‑presented poster at ASCO GU 2021.

This poster was entitled, "Treatment Patterns Among Patients with Advanced Urothelial Carcinoma Following Discontinuation of PD‑1 or PD‑L1 Inhibitor Therapy." The group and I put this poster together to really think about the treatment patterns of patients who have advanced metastatic or locally‑advanced urothelial carcinoma.

Unfortunately, that disease state remains incurable and tends to cause a large amount of suffering in patients as different treatments fail. There are not many lines of therapy that are actually available for patients, although there have been some newly‑approved treatments for patients with FGFR2 or 3 alterations, like erdafitinib, and enfortumab vedotin, which is a nectin‑4‑targeted antibody‑drug conjugate.

This study looked at what happened to patients who have locally‑advanced or metastatic urothelial carcinoma after they were treated with a checkpoint inhibitor to understand what kinds of treatments they received and how long they were on therapies.

In this study, we actually did retrospective chart review from 26 sites that were really geographically dispersed across the United States. This allowed us to get some more granular data than one can get from a claims‑based dataset, and it also allowed us to get patients from a broader array of ages, because it doesn't only include patients who are over 65, like the Medicare dataset.

In this particular study, we targeted to understand 300 patients to represent the locally‑advanced or metastatic or urothelial patient population. In this analysis, we tried to understand how PD‑1 and PD‑L1 inhibitors were actually used.

We found that, of the 300 patients, 66% actually received their PD‑1 or PD‑L1 inhibitor in the first‑line setting. In these patients, when we assessed them as compared to patients who received their PD‑1 or L1 in the second line, we found that patients were generally older when they received it in first line.

A greater proportion of them were actually staining positive for PD‑1 or PD‑L1 expression. In addition, they tended to have a higher ECOG performance status. In general, patients who received PD‑1 or PD‑L1 inhibitor therapy in the first line were older, had a poorer performance status, and did have a higher degree of staining for PD‑1 or PD‑L1.

Among patients who receive PD‑1 or PD‑L1 therapy in the first line, the median time on treatment was approximately 6 months. Approximately one‑third of them received subsequent therapy. Meaning, that approximately two‑thirds of patients who were treated with PD‑1 or L1 therapies did not receive a subsequent line of systemic therapy for their metastatic or locally‑advanced urothelial carcinoma.

Of those patients who received subsequent therapy, around 20% actually received another checkpoint inhibitor therapy, although there's no data to suggest that sequencing checkpoint inhibitor therapies will actually be effective.

Among patients who received PD‑1 or PD‑L1 therapy as a second‑line treatment, we found that patients had a median duration of PD‑1 or PD‑L1 therapy that was approximately 5 months. Approximately 29% of patients who received PD‑1 or L1 therapy actually received subsequent systemic therapy directed against their metastatic or locally‑advanced urothelial cancer in another line of therapy.

A majority of patients, again, were not receiving subsequent therapies. Of the patients who received subsequent therapies, again, approximately 20% actually received a subsequent PD‑1 or L1 inhibitor therapy.

Overall, approximately one‑fifth of our patients seemed to get a second PD‑1 or L1 inhibitor therapy after progression on an initial treatment. Again, there is no data to support that these treatments should be used in series, and really, there is no clear next‑line therapy that's been defined in the literature or in this study as the go‑to treatment after progression on a PD‑1 or PD‑L1 therapy.

Taxanes seemed to be used more commonly than other treatments, but there was no consensus. Ultimately, this study suggests that are a large number of patients who do not receive subsequent therapies after progression on PD‑1 or PD‑L1 therapy, leaving a large unmet need for patients to have disease control that's both effective and tolerable.

There are other therapies that have been approved, and these were approved too close to when this work was done to really evaluate their effectiveness and duration on therapy. Further work will need to define how other therapies, like erdafitinib and enfortumab vedotin, among others, will impact this treatment paradigm.

Morgans AK, Grewal SK, Hepp Z, et al. Treatment patterns among patients with advanced urothelial carcinoma following discontinuation of PD1/L1 inhibitor therapy. Presented at: the virtual 2021 ASCO Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 414.

Dr Morgans reports institutional research funding from Seattle Genetics and consultation payment from Astellas.

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