ASCO GU 2021: Treatment Patterns Among Patients with Advanced Urothelial Carcinoma Following Discontinuation of PD1/L1 Inhibitor Therapy

( Platinum-based cytotoxic chemotherapy has been the standard of care for patients with advanced urothelial carcinoma based on improved survival compared to placebo. However, objective response rates are at best 50% and median overall survival is relatively poor at less than 18 months. This has driven the rationale for additional approaches. In first-line (1L) therapy for patients who are not cisplatin-eligible and as maintenance or second-line therapy (2L) for patients receiving first-line chemotherapy, immune checkpoint therapy has become the standard of care. However, treatment for patients who have previously received programmed death 1/ligand 1 inhibitor (PD-1/L1i) therapy. 

In a poster presentation at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Morgans and colleagues presented the results of a retrospective chart review aimed at characterizing the clinical characteristics and treatments among patients with locally advanced and metastatic urothelial carcinoma following discontinuation of first-line or second-line PD-1/L1i therapy.

To do so, these authors performed a retrospective chart review at 26 geographically diverse clinical sites in the US to identify adult patients (aged 18 years and older) with histologically or cytologically confirmed urothelial carcinoma who had either radiographic evidence of metastasis or locally advanced disease. To be eligible for inclusion, patients must have had initiated and subsequently discontinued PD-1/L1i therapy as 1L or 2L treatment between May 15, 2016 and July 31, 2018, with follow-up through October 31, 2019. 

Dr. Morgans and colleagues identified 300 patients of whom 198 (66%) received PD-1/L1i therapy as 1L and 102 (34%) as 2L therapy. As expected based on the patient population, these patients were predominately older (mean age at diagnosis 69 years, SD 8.7 years), male (66.0%) and White (74.7%). Similarly, comorbidity rates were relatively high: 39.7% hypertension, 23.7% coronary artery disease, 17.7% pulmonary disease, and 9.3% renal disease. 

At the time of starting IO therapy, more patients who received IO therapy in the first-line setting (37%) had poor performance status (ECOG 2 or greater) as compared to those who received IO therapy in the second-line setting (23%). 

Following discontinuation of PD-1/L1i therapy, 68 patients (34%) received subsequent therapy in 2L and 30 patients (29%) in third-line (3L). The most common subsequent therapies in 2L were gemcitabine monotherapy (24%), gemcitabine plus cisplatin or carboplatin (22%), additional PD-1/L1i therapy (22%), and taxane monotherapy (19%). The most common subsequent therapies received in 3L were taxane monotherapy (50%), pemetrexed (17%), and additional PD-1/L1i therapy (16%). Approximately 1 in 5 patients switched from one PD-1/L1i therapy to another PD-1/L1i therapy.

The authors conclude that, in real-world practice at 26 sites, the majority of patients who discontinued PD-1/L1i therapy for advanced urothelial carcinoma did not receive further subsequent therapy. There was no standardized approach to subsequent therapy and differing IO approaches were relatively commonly employed. 

Presented by: Alicia K. Morgans, MD, MPH is an Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, @WallisCJD on Twitter during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021

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