Atezolizumab (atezo) vs. chemotherapy (chemo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): Immune biomarkers, tumor mutational burden (TMB), and clinical outcomes from the phase III IMvigor211 study.

Abstract

409 Background: IMvigor211 is a global study of atezo vs chemo in platinum-treated mUC. The study did not meet its primary endpoint of overall survival (OS) in programmed death-ligand 1 (PD-L1)–selected patients (pts),1 but exploratory analyses showed improved OS for atezo in the intent-to-treat (ITT) population. Here we compare clinical outcomes in ITT and prespecified PD-L1 subgroups with those in subgroups defined by immune transcriptional gene expression (tGE) signatures and TMB. Methods: Pts with ≤ 2 prior lines of therapy for mUC who progressed during or following platinum treatment were randomized 1:1 to atezo or chemo (vinflunine, paclitaxel or docetaxel, per physician). The primary endpoint was OS, hierarchically compared between treatment arms in PD-L1–selected and ITT pts. Planned exploratory biomarker analyses included tGE (RNA-seq) and TMB (FoundationOne). Results: The ITT population included 931 pts (atezo arm, 467; chemo arm, 464), and biomarker-evaluable subgroups were representative of the ITT population. PD-L1 expression positively correlated with tGE (R = 0.61) but not TMB (R = 0.13). OS and hazard ratios (HRs) are listed in the Table. Conclusions: In this randomized Phase III study, we show that high PD-L1 and high tGE are associated with improved outcomes with both chemo and atezo. In contrast, higher TMB predicted OS in favor of atezo; however, clinical benefit with atezo was also seen in the ITT population. Clinical trial information: NCT02302807. [Table: see text]