Is the occurrence of higher adverse effects associated with better oncological outcome in metastatic urothelial carcinoma patients treated with pembrolizumab?

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405 Background: Pembrolizumab is an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody and a recently approved and long-awaited drug for the treatment of metastatic urothelial carcinoma (UC). It is an immune checkpoint inhibitor, which has been shown to trigger new autoimmune disorders. We investigated the association of occurrence of adverse effects (AE) with clinical outcome in Japanese UC treated with pembrolizumab. Methods: We identified 50 cases treated with pembrolizumab for chemo-resistant UC between December 2017 and August 2018 at our 5 institutions. Pembrolizumab-induced AE were reported by using Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. We evaluated the association between pembrolizumab-induced AE and response rate as well as patient survival. Results: The median age of the patients was 73 years (range, 46-89 years). The male/female ratio was 36/14. The primary tumor location was the pelvis in 10, ureter in 10, and bladder in 30. The median course of pembrolizumab was 4 (1-11). In the 50 patients, 36 AEs were observed, 11 of which were classified as CTCAE grade 2/3 . These patients were defined as the high AE groups. No grade 4 AE was encountered. In the high AE groups the most common AE was adrenal dysfunction (n = 4). Patients with no or CTCAE grade 1 were defined as the no/low AE groups. In the 45 cases who had measurable lesions, at the point of maximum effect the sum of the target lesion longest diameter (SLD) was decreased in 17 cases (37.8%) compared to baseline. SLD decreased in 7 (70%) patients in the high AE groups, which was significantly lower than those in the no/low AE groups (10, 28.6%, p = 0.027). The disease control rate defined by RECST ver. 4.0 at best response in the high AE groups was 81.8%, which was significantly higher than that in the no/low AE groups (46.2%, p = 0.046). The 6-month progression-free survival rate and the 6-month cancer-specific survival rate for the high AE groups was not different from that for the no/low AE groups. Conclusions: In patients with metastatic UC, the occurrence of CTCAE grade 2/3 might be associated with a better clinical response to pembrolizumab treatment.