IMvigor210, Atezo in cis-ineligble

Background

Multicenter single-arm phase 2 trial (cohort 1); N=119 previously untreated cisplatin-ineligible patients with inoperable locally advanced or metastatic urothelial carcinoma (bladder, ureter, renal pelvis, urethra).

Interventions and follow up

Treatment: Atezolizumab 1200 mg IV q3wk until unacceptable toxicity or radiographic progression
Primary endpoint: Objective response rate (ORR)
Secondary: DOR, PFS, OS
mFollow up: 17.2 mo (5.8 yr in long-term update)

Results

ORR (all): 23%; by PD-L1 <1% vs 1–5% vs ≥5%: 21% vs 21% vs 28%.
CR: 10.1%.
mPFS (all): 2.7 mo; PD-L1 <1% vs 1–5% vs ≥5%: 2.6 vs 2.1 vs 4.1 mo.
mOS (all): 15.9 mo; PD-L1 <5% vs ≥5%: 12.3 vs 19.1 mo.
mDOR: NR at 17.2 mo (19/27 responses ongoing); 59.1 mo in long-term update.
Long-term update: mOS 16.3 mo; 24mo OS 41.1%; 60mo OS 21.6%.

Adverse events

Treatment-related G3–4: 16% of patients.
Grade 5 (treatment-related): 1 (sepsis).
Discontinuation (AE-related): 8% (9 patients).

Conclusions

First-line atezolizumab produced a 23% ORR (10% CR) with durable responses in cisplatin-ineligible advanced urothelial carcinoma, with a trend toward better response in PD-L1 ≥5%.

Key Limitations

Single-arm, no comparator; modest ORR; PD-L1 not predictive of benefit in first line; subsequent confirmatory data led to restriction of frontline single-agent checkpoint inhibitor use; the bladder indication was voluntarily withdrawn in the US in 2021.

Clinical Context

FDA granted accelerated approval for first-line atezolizumab in cisplatin-ineligible urothelial carcinoma (2017), later restricted to PD-L1-high; the bladder indication was voluntarily withdrawn in the US (2021) after failed confirmatory data. First-line standard is now enfortumab vedotin + pembrolizumab; ESMO/ASCO favor that combination over single-agent checkpoint inhibitor.

References