Introduction and Objectives: First-line (1L) treatment (tx) for mUC includes cisplatin (cis)- or carboplatin (carbo)-based chemotherapy or checkpoint inhibitors, depending on patient (pt)- and tumour-specific factors. IMvigor130 is a Phase 3, global, randomised, study of atezo (anti–PD-L1) alone or +PBC vs placebo+PBC in untreated mUC.

Materials and Methods: 1213 PBC-eligible mUC pts were enrolled. Randomisation was 1:1:1 to Arm A (atezo+PBC [gemcitabine (gem) + either cis or carbo]), Arm B (atezo) or Arm C (placebo+PBC). Gem 1000 mg/m2 IV was given on D1 and 8, carbo AUC 4.5 IV or cis 70 mg/m2 IV on D1 and atezo/placebo or atezo 1200 mg IV on D1 of each 3-wk tx cycle. Tumours were assessed at baseline and every 9 wk until INV-assessed PD per RECIST 1.1 or other events. Coprimary endpoints are INV-assessed PFS and OS (Arm A vs C) and OS (Arm B vs C, hierarchical approach) per RECIST 1.1. 

Results: Median final PFS was 8.2 vs 6.3 mo in Arm A vs C (HR, 0.82 [95% CI: 0.70-0.96]; P=0.007). The comparison of OS did not cross the prespecified interim efficacy boundary, with a median of 16.0 mo in Arm A and 13.4 mo in Arm C (HR, 0.83 [95% CI: 0.69-1.00]; P=0.027; Table). The median OS for Arm B vs C ITT pts was 15.7 vs 13.1 mo, respectively (HR, 1.02 [95% CI: 0.83-1.24]), and not estimable vs 17.8 mo, respectively (HR, 0.68 [95% CI: 0.43-1.08]), for Arm B vs C PD-L1 IC2/3 pts. ORRs were 47%, 23% and 44% and CR rates were 13%, 6% and 7% for Arms A, B and C, respectively. Tx withdrawal due to AEs occurred in 34%, 6% and 34% of pts in Arms A, B and C, respectively.

Conclusions: Atezo+PBC prolonged PFS vs PBC alone in untreated 1L mUC pts. The combination safety profile was consistent with that of atezo and PBC alone.

Table: Formally Tested Coprimary Endpoints
	Median PFS (95% CI), mo	
	        - Arm A Atezo+PBC (n=447): 8.2 (6.5-8.3)
		- Arm C Placebo+PBC (n=397): 6.3 (6.2-7.0)
	                 - HR (95% CI): 0.82 (0.70-0.96); P value: 0.007
	Median OS (95% CI), mo
		- Arm A Atezo+PBC (n=447): 16.0 (13.9-18.9)
		- Arm C Placebo+PBC (n=397): 13.4 (12.0-15.2)
	                 - HR (95% CI): 0.83 (0.69-1.00); P value: 0.027

Median follow-up = 11.8 mo; Data cutoff: 31 May 2019.
Stratification factors: tumour-infiltrating immune cell (IC) PD-L1 status (IC0 vs IC1 vs IC2/3), Bajorin risk factors/liver mets (0 vs 1 vs 2 or pts with liver mets), investigator-specified PBC (gem+carbo vs gem+cis).
PFS and OS for Arm A vs C were formally tested with type I error control for multiple comparisons with a prespecified interim efficacy boundary 
P value of 0.007; Arm B vs C in ITT and PD-L1 IC2/3 pts were not formally tested.
P values are 1-sided.

A Phase 3 study of atezolizumab (atezo) as monotherapy or combined with platinum-based chemotherapy (PBC) vs placebo + PBC in previously untreated locally advanced or metastatic urothelial carcinoma (mUC): IMvigor130