Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Clinical Experience from an Expanded Access Study in the United States

Background: Atezolizumab (anti–programmed death-ligand 1) was approved in the USA, Europe, and elsewhere for treatment-naive and platinum-treated locally advanced/metastatic urothelial carcinoma (mUC). Objective: To report efficacy and safety from an atezolizumab expanded access study. Design, setting, and participants: This single-arm, open-label study enrolled 218 patients at 36 US sites. Key eligibility criteria included progression during/following ≥1 platinum-based chemotherapy for mUC or in perioperative setting (progression within 12 mo) and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Intervention: Patients received atezolizumab1200 mg intravenously every 3 wk until loss of clinical benefit, unacceptable toxicity, consent withdrawal, decision to discontinue, death, atezolizumab commercial availability, or study closure. Outcome measurements and statistical analysis: Key end points reported herein included Response Evaluation Criteria in Solid Tumors v1.1 objective response rate and duration, disease control rate (DCR; response or stable disease), and safety. Results and limitations: All patients received prior systemic therapy (68% mUC; 27% adjuvant; and 26% neoadjuvant). At baseline, 57% of 214 treated patients had ECOG PS ≥1, 19% had hemoglobin <10 g/dl, and 25% had liver metastases. Median treatment duration was 9 wk (interquartile range [IQR], 6–12 wk). Median follow-up duration was 2.3 mo (IQR, 1.6–3.4 mo) overall and 2.7 mo (IQR, 2.0–3.5 mo) in patients not known to have died. Seventeen of 114 evaluable patients (15%) had objective responses (16 ongoing at study termination). DCR was 49%. Treatment-related adverse events (mostly fatigue) occurred in 98 of 214 treated patients. Conclusions: The benefit/risk profile of atezolizumab was consistent with that observed in previous studies, despite pretreatment and poor prognostic factors. These results suggest a potential role for atezolizumab in a broader patient range than typically eligible for phase 1–3 studies. Patient summary: In this expanded access study, atezolizumab was active and tolerable in a range of patients with platinum-treated metastatic urothelial carcinoma. In an expanded access study in platinum-treated advanced urothelial carcinoma, the benefit/risk profile of atezolizumab was consistent with previous trials despite a broader patient range than may be typical for phase 1–3 studies.