ASCO GU 2018: Atezolizumab vs. Chemotherapy in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma - Outcomes from the Phase III IMvigor211 Study

San Francisco, CA ( IMvigor211 is a global study of atezolizumab vs chemotherapy in platinum-treated metastatic urothelial carcinoma (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. In this study the authors compared clinical outcomes in ITT and pre-specified PD-L1 subgroups with those in subgroups defined by immune transcriptional gene expression (tGE) signatures and tumor mutational burden (TMB).


This was a randomized phase 3 study, where 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 overall survival (OS), hierarchically compared between treatment arms in PD-L1–selected and ITT pts. Planned exploratory biomarker analyses included tGE (RNA-seq) and TMB (FoundationOne).


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).


In this randomized Phase III study, it was demonstrated 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


Presented by: Thomas Powles, MD Barts Cancer Institute, Queen MARY University of London, UK

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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