Sumanta Kumar Pal1, Jean Hoffman-Censits2, Hanzhe Zheng3, Constanze Kaiser3, Darren Tayama3, Joaquim Bellmunt4. 1. City of Hope Comprehensive Cancer Center, Duarte, CA, USA. Electronic address: spal@coh.org. 2. Sidney Kimmel Cancer Center at Jefferson, Philadelphia, PA, USA. 3. Genentech, Inc., South San Francisco, CA, USA. 4. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: joaquim_bellmunt@dfci.harvard.edu.
Abstract
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 atezolizumab1200mg 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 <10g/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.
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 atezolizumab1200mg 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 <10g/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.
Authors: Zhengtian Li; Lingling Jiang; Rong Zhao; Jun Huang; Wenkang Yang; Zhenpei Wen; Bo Zhang; Gang Du Journal: Medicine (Baltimore) Date: 2021-05-28 Impact factor: 1.817
Authors: Alessandro Tafuri; David D Smith; Giovanni E Cacciamani; Sarah Cole; Aliasger Shakir; Sarmad Sadeghi; Nicholas J Vogelzang; David Quinn; Parkash S Gill; Inderbir S Gill Journal: Clin Genitourin Cancer Date: 2020-01-31 Impact factor: 3.121