Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC):...after prior platinum containing chemotherapy, or...who are considered cisplatin ineligible, and whose tumours have a PD-L1 expression ≥ 5%.

TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: Urothelial Carcinoma....for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who: are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 5% of the tumor area), as determined by an FDA-approved test.

...the NCCN Panel recommends pembrolizumab, atezolizumab, nivolumab, durvalumab, avelumab, or erdafitinib as preferred second-line systemic therapy options after platinum-based therapy. Atezolizumab and pembrolizumab are also recommended as preferred first-line therapy options for patients who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or in patients who are not eligible for any platinum containing chemotherapy regardless of PD-L1 expression for locally advanced or metastatic disease.

Atezolizumab or pembrolizumab are alternatives for patients with PD-L1 biomarker-positive tumours who are not eligible for cisplatin-based combination ChT.

Atezolizumab is recommended, within its marketing authorisation, as an option for untreated locally advanced or metastatic urothelial cancer in adults whose tumours express PD-L1 at a level of 5% or more and when cisplatin-containing chemotherapy is unsuitable.

PD-L1 IC 2/3 status is associated with longer OS in cis- but not carbo-treated pts with mUC...cis/gem induces immunogenic cell death and enhances antitumour immunity, particularly when combined with atezo.

...in pts with PD-L1-expressing immune cells on ≥5% of the tumor area (IC2/3 per VENTANA SP142 IHC assay….Pts were randomized 1:1:1 to Arm A (atezo + plt/gem [not reported here]), B or C....Exploratory subgroup analyses suggested that OS for IC2/3 pts may be higher in Arm B vs C. In ITT pts, ORR was higher in Arm C, but median DOR was longer in Arm B....benefit of atezo monotherapy as first-line treatment for PD-L1 IC2/3 cisplatin-ineligible mUC..

PD-L1 IC2/3 was associated with significantly longer OS for atezo mono vs placebo + PBC and a combination of PD-L1 IC2/3, and high TMB (> 10 muts/Mb) identified a pt subset (≈ 14% of BEP) with particularly favorable outcomes with atezo mono vs placebo + PBC; similar results for PD-L1 and TMB were not seen with atezo + PBC vs placebo + PBC.

...Representative formalin-fixed paraffin embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor PD L1 expression prior to study enrollment...

The phase Ib/II MORPHEUS-UC trial (NCT03869190) is evaluating atezolizumab plus magrolimab, niraparib, or tocilizumab in platinum-refractory locally advanced or metastatic (mUC)....Trends were observed for shrinkage of PD-L1+ tumors (atezolizumab, atezolizumab plus magrolimab, atezolizumab plus tocilizumab)…

PD-L1 positive pts had superior OS (logrank p=0.06) and RFS (p=0.10) relative to PD-L1 negative pts.

Patients with metastatic urinary tract carcinoma received atezolizumab 1,200 mg every 3 weeks until disease progression...Patients with PD-L1 expression on ≥5% of tumor-infiltrating immune cells tended to have better outcomes than those with <5% PD-L1 expression...

Patients were given 1200 mg intravenous atezolizumab every 21 days until progression…119 received one or more doses of atezolizumab. At 17·2 months' median follow-up, the objective response rate was 23% (95% CI 16 to 31), the complete response rate was 9% (n=11), and 19 of 27 responses were ongoing...Responses occurred across all PD-L1 and poor prognostic factor subgroups...Atezolizumab showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated metastatic urothelial cancer.