PD1/L1 inhibitors are approved by FDA as first-line therapy for patients with advanced urothelial carcinoma (aUC) who are cisplatin-ineligible with high tumor PD-L1 expression or are platinum-ineligible regardless of PD-L1 expression.
However, the outcomes when employing PD1/L1 inhibitors for platinum-ineligible patients are unclear. This retrospective analysis evaluates the clinical outcomes of first-line PD1/L1 inhibitors in patients with aUC deemed to be platinum-ineligible.
Data were retrospectively collected from 8 academic institutions. The following criteria were used to define platinum ineligibility: creatinine clearance (CrCl) < 30 mL/min; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 3; CrCl 30 to 59 mL/min and ECOG PS 2; elderly and/or comorbidities. Patient characteristics, responses and treatment-related toxicities were identified. Survival curves were estimated by the Kaplan-Meier method. A Cox regression analysis was conducted to explore the association of baseline variables with response and survival.
A total of 79 platinum-ineligible patients with aUC were eligible. Patients were treated with atezolizumab (51.9%), pembrolizumab (35.5%), nivolumab (8.9%), or durvalumab (3.8%). The objective response rate was 27.9%. The median overall survival was 45 weeks (95% confidence interval [CI], 32-80), and the median treatment failure-free survival was 16 weeks (95% CI, 9-18). Treatment-related toxicity of any grade and grade ≥ 3 was seen in 41.8% and 31.7% of patients, respectively. Anemia and liver metastasis were associated with worse survival.
The efficacy of first-line PD1/L1 inhibitors for platinum-ineligible patients with aUC in the real world appears comparable to those reported in trials of unselected cisplatin-ineligible patients, whereas grade ≥ 3 toxicities appear more common. Further validation is required including data based on PD-L1 status and other biomarkers. Platinum-ineligible patients with aUC warrant evaluation of novel, safe, and effective agents.
Clinical genitourinary cancer. 2021 Apr 20 [Epub ahead of print]
Gregory R Pond, Archana Agarwal, Moshe Ornstein, Jorge Garcia, Ruby Gupta, Petros Grivas, Alexandra Drakaki, Jae-Lyun Lee, Ravindran Kanesvaran, Giuseppe Di Lorenzo, Pasquale Verolino, Pedro Barata, Mehmet A Bilen, Syed A Hussain, Catherine Curran, Guru Sonpavde
McMaster University, Hamilton, ON, Canada., St. Vincent Hospital, Worcester, MA., Cleveland Clinic Taussig Cancer Institute, Cleveland, OH., University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA., University of California, Los Angeles, CA., Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea, Republic of (South)., National Cancer Center, Singapore., University of Naples Federico II, Napoli, Italy; University of Molise, Campobasso, Italy., Tulane University, New Orleans, LA., Emory University, Atlanta, GA., University of Sheffield, Sheffield, England, UK., Dana-Farber Cancer Institute, Boston, MA., Dana-Farber Cancer Institute, Boston, MA. Electronic address: .