Early switching to pembrolizumab (Pe) during first-line platinum-based chemotherapy (PCT) in patients (pts) with metastatic urothelial carcinoma (mUC).

Abstract

452 Background: With the results of the Javelin bladder 100 trial, PCT followed by ICI has become the standard of care for pts with mUC. While more than half of the pts have progressive disease (PD) by the 4th cycle of PCT, in general, most these pts will receive ICI after 4th cycle of PCT. However, for pts who have PD before 4 cycles, additional PCT will not only be effective, but will also cause side effects and worsen immune environment. However, the outcome of early switching to ICI during 1st-line PCT has not been reported. Here, we investigated whether early switching to Pe may improve prognosis. We also examined the usefulness of serum CYFRA (sCY) as a prognostic marker of 2nd-line Pe in this study. Methods: Seventy pts with mUC received PCT followed by Pe from February 2018 to July 2022 at our institution. Among them 56 pts who had received PCT 3 cycles or less because of PD or unacceptable side effects were included in this study. During PCT, computed tomography (CT) was performed at the end of each cycle and PCT was continued until PD. If PD on CT was confirmed, 2nd-line Pe was initiated. Performance status, metastasis site, neutrophil-lymphocyte ratio, hemoglobin, and serum alkaline phosphatase, C-reactive protein, total protein, albumin, corrected calcium (Ca) and sCY before Pe were examined as possible prognostic factors for overall survival (OS). OS was analyzed by Kaplan-Meier curves and log-rank test. Multivariate analysis on prognostic factors was carried out using the Cox hazards model. Results: Median age was 73 (31-86). Twenty-seven pts (49%) received gemcitabine-cisplatin and 29 (51%) received gemcitabine-carboplatin for PCT. Twelve pts (21%) received 1 cycle of PCT, 2 cycles in 26 (46%) and 3 cycles in 18 (32%). During the median follow-up period of 14.6 (6.2-44.6) months (M), 30 pts (53.5%) had died. The median OS was 15.5M and the 1-year OS rate was 60%. The median PFS was 10.2M and the 1-year PFS rate was 46%. Objective response rate was 25% and 18 pts showed stable disease (32%) and 24 pts (43%) showed PD. On univariate analysis, sCY (p=0.001) and Ca (p=0.003) were the significant factors for OS. On multivariate analysis, sCY (HR 3.2, 95%CI [1.33-7.82], p=0.009) and Ca (HR2.3, (95%CI [1.02-5.22], p=0.046) were the significant factors for OS. Conclusions: Early switching to Pe during 1st-line PCT resulted in PFS of 10.2M and OS of 15.5M, which were longer than those of the KEYNOTE-045 trial (PFS 2M, OS 10M). Early introduction of Pe may be effective in the pts with mUC who are resistant to chemotherapy. sCY and Ca were suggested to be the useful prognostic factors for OS.