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Post hoc analysis of the efficacy of pembrolizumab retreatment after progression of advanced urothelial carcinoma (UC) in KEYNOTE-045 and KEYNOTE-052.

512 Background: Pembrolizumab (pembro) has shown efficacy in advanced/unresectable and metastatic UC (mUC). There is interest in determining whether pts should be treated subsequently with checkpoint inhibitors such as anti–PD-1 therapy if mUC responds then later progresses. Pembro retreatment after disease progression has shown efficacy in melanoma and NSCLC. This post hoc exploratory analysis investigated the efficacy of pembro retreatment for pts with advanced UC or mUC enrolled in KEYNOTE-045 and KEYNOTE-052 with a best overall response (BOR) of SD or better and whose disease progressed after discontinuation or completion of 2 y of therapy. Methods: The phase 3 KEYNOTE-045 trial (NCT02256436) was designed to compare the efficacy and safety of pembro vs chemotherapy (chemo) in pts with mUC that recurred/progressed on platinum containing chemo; ≤2 prior lines of systemic chemo for mUC were permitted. The phase 2 KEYNOTE-052 trial (NCT02335424) was designed to evaluate the efficacy and safety of first-line pembro in cisplatin-ineligible pts with advanced UC. In both studies, pembro was administered for up to 2 y; pts were eligible for retreatment if they stopped pembro after CR or had a BOR of CR, PR, or SD and completed 2 y of treatment. Pts must have investigator-confirmed radiographic PD after therapy cessation, have ECOG PS score 0-1, and not have received anticancer treatment after the last pembro dose. BOR to retreatment is reported. Results: At data cutoff for KEYNOTE-045 (Oct 1, 2020), 11 pts were retreated: 5 (45%) achieved objective response to retreatment (3 CR; 2 PR; Table) and 6 had SD, for a disease control rate (DCR; CR+PR+SD) of 100%. Median treatment-free interval was 7.7 mo (IQR, 3.6-16.5); median duration of retreatment was 11.4 mo (IQR, 7.6-12.0). Seven pts (64%) were alive at cutoff. At data cutoff for KEYNOTE-052 (Sep 26, 2020), 10 pts were retreated; 5 (50%) had objective response to retreatment (1 CR; 4 PR) and 4 had SD, for a DCR of 90%. Retreatment BOR was PD for 1 pt (10%). Median treatment-free interval was 13.0 mo (9.2-16.6); median duration of retreatment was 6.0 mo (IQR, 4.9-9.2). Four pts (40%) were alive at cutoff. Conclusions: Although the number of pts who received retreatment was small, objective responses were observed. The findings are generally consistent with observations from retreatment in other tumor types (e.g., melanoma). Clinical trial information: NCT02256436 and NCT02335424. [Table: see text]