In the phase III KEYNOTE-361 study, investigators assessed first-line treatment with pembrolizumab, with or without chemotherapy, versus chemotherapy alone in patients with advanced urothelial carcinoma (UC), regardless of PD-1 status. Presented in Poster Session B: Urothelial Carcinoma at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, lead author Rafael Morales-Barrera, MD, reported that first-line pembrolizumab monotherapy had strong associations between tumor mutational burden (TMB) and overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), whereas “a reduced association was observed between TMB and clinical outcomes with pembro + chemo.”
Notably, the study did not meet its primary endpoints of superior PFS and OS in pembrolizumab plus chemotherapy versus chemotherapy alone, which caused the analysis of pembrolizumab monotherapy versus chemotherapy to be exploratory only.
The final trial divided a total of 993 patients into three arms: pembrolizumab monotherapy (252), pembrolizumab plus chemotherapy (282), and chemotherapy alone (286). In pembrolizumab monotherapy, TMB had a significant positive correlation with ORR (p <0.001), PFS (p <0.001), and OS (p <0.007), while pembrolizumab plus chemotherapy was only associated with PFS (p = 0.007) and OS (p = 0.010). Additionally, PD-L1 was significantly positively associated with PFS in pembrolizumab alone (p = 0.006), and with ORR in pembrolizumab plus chemotherapy (p = 0.042).
Although Dr. Morales-Barrera relayed that “no consistent associations were observed between PD-L1 and clinical outcomes with pembro mono or pembro + chemo,” the significant associations between TMB and ORR, PFS, and OS with pembrolizumab monotherapy might suggest that monotherapy is the optimal treatment strategy, fully foregoing chemotherapy in patients with advanced UC.