PURPOSE Immune checkpoint inhibitors combined with platinum-based chemotherapy is standard in patients with advanced/metastatic urothelial carcinoma (mUC). Cisplatin has immunomodulatory benefits compared with carboplatin. This study aims to assess the safety and efficacy of atezolizumab and a split-dose cisplatin regimen in patients ineligible for full doses of cisplatin. PATIENTS/METHODS The phase II single-arm SOGUG-AUREA clinical trial recruited treatment-naïve patients with mUC ineligible for full dose of cisplatin because of elderly, poor performance status, or impaired renal function. Patients received cisplatin (35 mg/m 2 ) and gemcitabine (1,000 mg/m 2 ) on days 1 and 8, up to six cycles, in combination with atezolizumab 1,200 mg intravenously once every 3 weeks until progression, unacceptable toxicity, or absence of clinical benefit. The primary end point was objective response (OR). Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. A Fleming's two-stage design was used with a total enrollment of 66 patients required (null and alternative hypothesis: OR, 30% v 50%; α = .05; β = 80%). RESULTS Between January 2021 and March 2022, 66 patients were included. The OR was 48.5% (95% CI, 36 to 61), with seven (10.61%) patients experiencing complete response. The median DoR was 9.2 months (95% CI, 5.5 to 16.8+). After a median follow-up of 11.6 months (range, 0.6-35.3), median PFS was 6.9 months (95% CI, 6.7 to 9.4), with 12-month PFS rate of 31.0% (95% CI, 21.4 to 44.8). The median OS was 12.9 months (95% CI, 10.2 to 20.2), with a 24-month OS rate of 30.1% (95% CI, 20.6 to 44.0). Most frequent grade 3 to 4 toxicities were neutropenia (31.8%), anemia (25.8%), and thrombocytopenia (19.7%). CONCLUSION Atezolizumab plus split doses of cisplatin and gemcitabine showed durable responses and promising OR in patients with mUC. Safety profile was consistent with previous experience.
Velasco et al. (Tue,) studied this question.