Abstract CT042: Atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs placebo + plt/gem in patients (pts) with previously untreated locally advanced or metastatic urothelial carcinoma (mUC): Updated overall survival (OS) from the randomized phase III study IMvigor130
Authors: Galsky Matthew D. , Arranz José Ángel , Grande Enrique , De Santis Maria , Davis Ian D. , Kikuchi Eiji , Garcia del Muro Xavier , Park Se Hoon , De Giorgi Ugo , Alekseev Boris , Mencinger Marina , Izumi Kouji , Puente Javier , Li Jian-Ri , O'Donnell Peter H. , Shen Xiaodong , Lee Chooi , Mecke Almut , Mariathasan Sanjeev , Bamias Aristotelis 
Published: July 2021

Abstract
Background: The IMvigor130 primary analysis demonstrated a statistically significant progression-free survival (PFS) benefit and encouraging OS with atezo + plt/gem (Arm A) vs placebo + plt/gem (Arm C) as first-line mUC treatment, although interim OS results did not cross the pre-specified threshold for significance (Galsky Lancet 2020). Here we report the 2nd interim OS for Arm A vs C, including efficacy by type of chemotherapy (chemo) given.
Methods: Pts were randomized 1:1:1 to Arm A, B (atezo monotherapy) or C. Investigators pre-specified the type of chemo pts would receive if assigned to Arms A or C (gem + either cisplatin or carboplatin). Co-primary endpoints (EPs) were RECIST 1.1 PFS and OS (Arm A vs C; ITT) and OS (Arm B vs C; ITT, IC2/3) tested using a hierarchical approach. Safety and secondary efficacy EPs (objective response rate and duration of response) are reported. Exploratory OS analyses by type of chemo were pre-specified.
Results: As of data cutoff, June 14, 2020 (median follow-up, 13.3 mo), OS event rates were 67% in Arm A and 70% in Arm C. Efficacy data are shown (Table). Subsequent non-protocol immunotherapy use was 7% in Arm A vs 24% in Arm C. Of pts in the safety population (Arm A: 454; Arm C: 389), 81% and 80%, respectively, had a Gr 3/4 treatment-related AE (TRAE). No new Gr 5 TRAEs occurred since the 1st analysis (Gr 5 TRAEs: 2% in Arm A vs 1% in Arm C). Gr 3/4 AEs of special interest occurred in 9% in Arm A and 4% in Arm C.
Conclusions: OS with atezo + plt/gem vs placebo + plt/gem in this updated analysis of IMvigor130 was consistent with the 1st interim analysis (not yet statistically significant). The impact of atezo plus chemo on outcomes may differ based on the specific platinum regimen; these exploratory findings warrant further investigation. OS follow-up is ongoing. Safety profile of atezo + plt/gem was consistent with each agent.
IMvigor130 efficacy (second interim OS analysis)Arm A:Arm C:atezo + plt/gemplacebo + plt/gem(n=451)(n=400)OS HR (95% CI)aITT0.84 (0.71, 1.00); P=0.026bCisplatin (n=273)0.73 (0.54, 0.98)PD-L1 IC2/3 (n=69)c0.66 (0.32, 1.36)PD-L1 IC0/1 (n=204)c0.72 (0.52, 1.01)Carboplatin (n=578)0.91 (0.74, 1.10)PD-L1 IC2/3 (n=130)c0.80 (0.52, 1.23)PD-L1 IC0/1 (n=448)c0.94 (0.75, 1.18)Median OS (95% CI), moITT16.1 (14.2, 18.8)13.4 (11.9, 15.2)Cisplatin21.6 (17.5, 25.4)14.6 (11.7, 18.4)Carboplatin14.3 (12.0, 16.5)13.0 (10.6, 15.2)Objective response rate (95% CI), %ITT (n=844)d48 (43, 53)45 (40, 50)Cisplatin (n=271)d49 (40, 57)50 (41, 58)Carboplatin (n=573)d48 (42, 53)42 (36, 48)Complete response rate (95% CI), %ITT (n=844)d13 (10, 17)7 (5, 10)Cisplatin (n=271)d17 (11, 24)9 (5, 15)Carboplatin (n=573)d12 (9, 16)6 (4, 10)Median duration of response (95% CI), moeAll responders (n=391)9.3 (8.0, 10.7)8.2 (6.3, 8.5)Cisplatin (n=133)13.2 (10.4, 22.5)8.3 (6.3, 13.3)Carboplatin (n=258)8.1 (6.5, 10.2)7.1 (6.2, 8.5)IC, tumor-infiltrating immune cells; ITT, intention to treat.aHR for the ITT population is stratified by PD-L1 IC status (IC0 vs IC1 vs IC2/3), Bajorin risk factor score (0, 1, 2 and/or liver metastases), investigator's choice of cisplatin/gemcitabine vs carboplatin/gemcitabine and enrollment stage. HRs for subgroups are stratified by enrollment stage.bOne-sided; not statistically significant (O'Brien-Fleming stopping boundary P value 0.014).cPD-L1-expressing IC covering ≥5% (IC2/3) or &lt;5% (IC0/1) of the tumor area per VENTANA SP142 IHC assay.dFor objective response analyses, only pts with measurable disease at baseline were included (n=844 of 851). e In patients who had a response.
Citation Format: Matthew D. Galsky, José Ángel Arranz, Enrique Grande, Maria De Santis, Ian D. Davis, Eiji Kikuchi, Xavier Garcia del Muro, Se Hoon Park, Ugo De Giorgi, Boris Alekseev, Marina Mencinger, Kouji Izumi, Javier Puente, Jian-Ri Li, Peter H. O'Donnell, Xiaodong Shen, Chooi Lee, Almut Mecke, Sanjeev Mariathasan, Aristotelis Bamias. Atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs placebo + plt/gem in patients (pts) with previously untreated locally advanced or metastatic urothelial carcinoma (mUC): Updated overall survival (OS) from the randomized phase III study IMvigor130 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT042.