Pembrolizumab Efficacy in Platinum-Ineligible Urothelial Carcinoma

The initial treatment of choice for advanced urothelial carcinoma in the United States for patients who are not eligible for platinum-based therapy is pembrolizumab monotherapy. The absence of a universally accepted criterion for platinum ineligibility necessitates clinical discretion when making treatment determinations. It is pertinent to ascertain whether the effectiveness of Pembrolizumab in treating UC exhibits variability depending on the criteria employed to define ineligibility for platinum. This retrospective analysis combined patients who received pembrolizumab monotherapy from the KEYNOTE-052 (N=370; NCT02335424) and LEAP-011 (N=242; NCT03898180) studies. These patients were identified as potentially ineligible for platinum-based therapy based on criteria established through a comprehensive review of published literature. The literature has identified certain candidate criteria that render an individual ineligible for platinum. These include an ECOG PS of 2, renal dysfunction with a GFR of less than 60 mL/min, the presence of visceral disease, and an age of 80 years or older. For this analysis, subgroups of patients exhibiting various combinations of the following criteria were selected: Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 (with or without age greater than or equal to 80 years, renal dysfunction, or visceral disease); age greater than or equal to 80 years with renal dysfunction; or visceral disease (with or without age greater than or equal to 80 years or renal dysfunction). The efficacy endpoints comprised overall response rate (ORR) and overall survival (OS).

The cut-off dates for the databases were September 26, 2020, for KEYNOTE-052 and July 26, 2021, for LEAP-011. The median follow-up duration was 56.3 months (51.2-65.3) for KEYNOTE-052 and 7.0 months (0.2-25.0) for LEAP-011. The primary analyses indicate that the overall response rate (ORR) with a 95% confidence interval (CI) was 28.9% (24.3-33.8) in KEYNOTE-052 and 28.9% (23.3-35.1) in the pembrolizumab monotherapy arm of LEAP-011. The median OS with a 95% CI was 11.3 (9.7-13.1) and 12.9 (9.8-17.8) months, respectively. The observed response rate (ORR) was 23.5% to 33.3%, while the median OS ranged from 9.0 to 10.6 months across the subgroups. In this exploratory analysis conducted post hoc, it was observed that patients with UC responded to pembro monotherapy irrespective of the criteria employed to determine platinum ineligibility. The median OS demonstrated a uniform pattern across subgroups and was comparable to that of the entire patient cohort.

Source:https://oncologypro.esmo.org/meeting-resources/esmo-congress/post-hoc-analysis-of-pembrolizumab-efficacy-in-potentially-platinum-ineligible-patients-with-urothelial-carcinoma-enrolled-in-keynote-052-and-leap-011

Clinical Trail:https://clinicaltrials.gov/ct2/show/NCT03898180

Y. Loriot, T. Csoszi, N. Matsubara, S.J. Shin, S.H. Park, V. Atduev, M. Gumus, B.B. Karaca, P. Grivas, R. De Wit, A.O. Siefker-Radtke, D.E. Castellano Gauna, P.H. O’Donnell, T.B. Powles, J. Vuky, Y. Zhao, K. O’hara, S. Franco, B. Homet Moreno, J. Zolnierek/Post hoc analysis of pembrolizumab efficacy in potentially platinum ineligible patients with urothelial carcinoma enrolled in KEYNOTE-052 and LEAP-011/Annals of Oncology (2022) 33 (suppl_7): S785-S807. 10.1016/annonc/annonc1080