Characterization of outcomes in patients with advanced genitourinary malignancies treated with immune checkpoint inhibitors

• Published in: Urologic oncology 2021-07, Vol.39 (7), p.437.e1-437.e9
• Main Authors: Ma, Vincent T., Su, Christopher T., Hu, Miriam, Taylor, Jeremy M.G., Daignault-Newton, Stephanie, Kellezi, Olesia, Dahl, Megan N., Shah, Miloni A., Erickson, Stephanie, Lora, Jessica, Hamasha, Reema, Ali, Alicia, Yancey, Sabrina, Kiros, Leah, Balicki, Hannah M., Winfield, Daniel C., Green, Michael D., Alva, Ajjai S.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Cohort Studies; Female; Genitourinary malignancy; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immune-related adverse events; Liver metastases; Male; Middle Aged; Neoplasm Staging; Progression-Free Survival; Renal cell carcinoma; Retrospective Studies; Treatment Outcome; Urogenital Neoplasms - drug therapy; Urogenital Neoplasms - pathology; Urothelial carcinoma
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2021.01.006

•Among various sites of metastases, liver metastases portend a worse survival outcome for genitourinary (GU) malignancy patients treated with immune checkpoint inhibitor (ICI) therapy.•Patients who experienced increased frequency and higher grade immune-related adverse events are associated with better ICI treatment response.•Pre-existing immune-mediated allergies may be associated with better ICI treatment response rates, but this finding warrants a larger cohort assessment.•Comorbidity indices do not appear to be reliable markers for survival in GU malignancy patients treated with ICI. Several immune checkpoint inhibitors (ICIs) are FDA approved for treatment of genitourinary (GU) malignancies. We aim to determine demographic and clinicopathologic characteristics that significantly affect clinical outcomes in patients with advanced stage GU malignancies treated with ICIs. We performed a single-center, consecutive, retrospective cohort analysis on patients with metastatic or unresectable GU malignancies who were treated with ICIs at the University of Michigan. Immune-related adverse events (irAEs), putative immune-mediated allergies, and overall response rates (ORR) were assessed. Comorbidity index scores were calculated. Survival analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS), stratifying and controlling for a variety of clinicopathologic baseline factors including site of metastases. A total of 160 patients were identified with advanced renal cell carcinoma (RCC) or urothelial carcinoma. Median PFS and OS were 5.0 and 23.6 months for RCC, and 2.8 and 9.6 months for urothelial carcinoma, respectively. Patients who experienced increased frequency and higher grade irAEs had better ICI treatment response (P < 0.0001). Presence of liver metastases was associated with poor response to ICI therapy (P = 0.001). Multivariable modeling demonstrates that patients with urothelial carcinoma and liver metastases had statistically worse PFS and OS compared to patients with RCC or other sites of metastases, respectively. Greater frequency and higher grades of irAEs are associated with better treatment response in patients with RCC and urothelial malignancy receiving ICI therapy. The presence of liver metastases denotes a negative predictive marker for immunotherapy efficacy. Immune checkpoint inhibitors (ICI) are increasingly used to treat genitourinary (GU) malignancies. However, clinical data regarding patients with advan