First-line PD(L)1 inhibitors for platinum-ineligible advanced urothelial carcinoma (aUC).
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e16024 Background: FDA modified the label for 1st-line pembrolizumab or atezolizumab to PD-L1 high cisplatin-ineligible or platinum-ineligible aUC patients (pts) regardless of PD-L1 expression. However, the outcomes when using PD-(L)1 inhibitors for platinum-ineligible pts are unclear. We hypothesized that treatment response and outcomes are comparable to data reported in trials in the 1st line setting of aUC, and conducted a retrospective study to test this hypothesis using data outside the clinical trial setting. Methods: We collected data from 8 institutions for aUC pts with locally advanced unresectable or metastatic UC. The following criteria were used to define pts platinum-ineligible while comorbidities, age and physician discretion were also allowed: Cr Cl < 30 ml/min, ECOG PS 3, Cr Cl 30-59 ml/min and ECOG PS 2. Demographic & clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. A Cox regression analysis was used to explore associations of baseline variables with response and outcomes. Results: Data were available for 79 pts. Pts received atezolizumab [n = 41], pembrolizumab [n = 28], nivolumab [n = 7] or durvalumab [n = 3]. Median age was 74 years (45-93). Reasons for platinum-ineligibility were: Cr Cl < 30 ml/min (n = 26), ECOG PS 3 (n = 8), ECOG-PS 2 and Cr Cl < 30-59ml/min (n = 14), elderly/co-morbidities (n = 17), and ‘unavailable’ (n = 14). Median OS was 45 weeks (CI 32-80) and ORR was 27.9%: Complete response in 4 pts [5.1%], partial response in 18 pts [22.8%], stable disease in 19 pts [24.1%], progressive disease in 34 pts [43 %]; data for 4 pts [5.1%] was unavailable for best response. Toxicity of any grade and Grade ≥3 was seen in 41.8% and 31.7% of pts, respectively. Hemoglobin (HR = 0.78, 95% CI 0.68 - 0.90, P = 0.001) and liver metastasis (HR = 1.13, 95% CI 0.51 - 2.53, P = 0.036) correlated with OS. Conclusions: The efficacy and toxicities of 1st-line PD-(L)1 inhibitors for platinum-ineligible pts outside clinical trials appear comparable to those reported in trials for unselected cisplatin-ineligible pts. Further validation is required including data based on PD-L1 status and other biomarkers. Platinum-ineligible pts with aUC warrant evaluation of novel safe and effective agents.
