A multicenter real-life U.K. study of use of immunotherapeutic agents in metastatic urothelial cancer.

Abstract

504 Background: First-line chemotherapy for patients with cisplatin-ineligible metastatic urothelial carcinoma (mUC) is associated with short response duration and high toxicity. Pembrolizumab(PEM) and atezolizumab (ATZ) are associated with long-term, durable remissions as a first-line treatment of cisplatin-ineligible, PD-L1-positive patients with mUC. For patients who progressed during or after platinum-based chemotherapy, Immunotherapy also prolongs survival with less toxicity and better quality of life compared with further lines of chemotherapy. There have been no studies directly comparing the effectiveness of PEM to ATZ in mUC patients. Methods: A cohort of 112 patients from 3 UK centres were included. 62, previously untreated cisplatin ineligible mUC patients who showed PDL1 positivity were given either ATZ or PEM once every 3 weeks until progression. 49 patients who had initial platinum based chemotherapy subsequently had ATZ or PEM as second line treatment following their disease progression The primary endpoint was Overall Survival(OS) and secondary endpoints included objective rate(ORR), response duration and safety. Results: The median age was 69 ( Interquartile range 43-91) and 23% were female and 77% were male. Among, patients who received immunotherapy 1st line, 82% had baseline renal impairment(GFR < 60), and 18% had Eastern Cooperative Oncology Group performance status 2. For chemo naïve patients, median OS was 11.5 months for PEM and 5 months for ATZ respectively. ORR was 22 % for ATZ vs 50% for PEM and median duration of treatment was 4.5 and 2.5 months for PEM and ATZ respectively. When used in 2nd line median OS is 7 months for ATZ irrespective of PDL1 status and not reached for PEM yet. Grade 2 and above toxicities were reported in 18 % ATZ patients vs 10% in PEM patients, commonest were pneumonitis, tiredness, hepatitis and dermatitis. No treatment related deaths were reported. Conclusions: This study suggests that pembrolizumab has higher response rate and better survival compared to atezolizumab in cisplatin-ineligible patients with mUC and also in the 2nd line setting after disease progression following platinum based agents. Both agents were well tolerated.