TY - JOUR
T1 - Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma
T2 - Outcomes by Prior Number of Regimens
AU - Perez-Gracia, Jose Luis
AU - Loriot, Yohann
AU - Rosenberg, Jonathan E.
AU - Powles, Thomas
AU - Necchi, Andrea
AU - Hussain, Syed A.
AU - Morales-Barrera, Rafael
AU - Retz, Margitta M.
AU - Niegisch, Günter
AU - Durán, Ignacio
AU - Théodore, Christine
AU - Grande, Enrique
AU - Shen, Xiaodong
AU - Wang, Jingjing
AU - Nelson, Betty
AU - Derleth, Christina L.
AU - van der Heijden, Michiel S.
N1 - Publisher Copyright:
© 2017
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Background: Patients with metastatic urothelial carcinoma (mUC) who progress after platinum-based chemotherapy have had few treatment options and uniformly poor outcomes. Atezolizumab (anti-programmed death-ligand 1) was approved in the USA for cisplatin-ineligible and platinum-treated mUC based on IMvigor210, a phase 2, single-arm, two-cohort study. Objective: To evaluate the efficacy and safety of atezolizumab by the number of prior lines of systemic therapy in patients with pretreated mUC. Design, setting, and participants: IMvigor210 enrolled 315 patients with mUC with progression during or following platinum-based therapy at 70 international sites between May 2014 and November 2014. Key inclusion criteria included age ≥18 yr, creatinine clearance ≥30 ml/min, and Eastern Cooperative Oncology Group performance status 0–1, with no limit on prior lines of treatment. Intervention: Patients in this cohort received atezolizumab 1200 mg intravenously every 3 wk until loss of clinical benefit. Outcome measurements and statistical analysis: Centrally assessed Response Evaluation Criteria In Solid Tumors v1.1 objective response rate (ORR), median duration of response, overall survival (OS), and adverse events were evaluated by prior treatment. Potential differences between subgroups were evaluated using log-rank (for OS) and chi-square (for ORR and adverse events frequencies) testing. Results and limitations: Three hundred and ten patients were efficacy and safety evaluable (median follow-up, 21 mo). Objective responses and prolonged OS occurred across all prespecified subgroups; median duration of response was not reached in most subgroups. In patients without prior systemic mUC therapy (first-line subgroup), ORR was 25% (95% confidence interval: 14–38), and median OS was 9.6 mo (95% confidence interval: 5.9–15.8). No significant differences in efficacy or toxicity by therapy line were observed. Conclusions: Atezolizumab demonstrated comparable efficacy and safety in previously treated patients with mUC across all lines of therapy evaluated. Patient summary: We investigated effects of previous treatment in patients with metastatic urothelial carcinoma that progressed after platinum-based therapy. Atezolizumab was active and tolerable no matter how many treatment regimens patients had received. ClinicalTrials.gov, NCT02108652. Outcomes by prior regimens were examined in a phase 2 atezolizumab study in platinum-treated urothelial carcinoma. Atezolizumab demonstrated comparable efficacy and safety in previously treated patients with metastatic urothelial carcinoma across all lines of therapy evaluated.
AB - Background: Patients with metastatic urothelial carcinoma (mUC) who progress after platinum-based chemotherapy have had few treatment options and uniformly poor outcomes. Atezolizumab (anti-programmed death-ligand 1) was approved in the USA for cisplatin-ineligible and platinum-treated mUC based on IMvigor210, a phase 2, single-arm, two-cohort study. Objective: To evaluate the efficacy and safety of atezolizumab by the number of prior lines of systemic therapy in patients with pretreated mUC. Design, setting, and participants: IMvigor210 enrolled 315 patients with mUC with progression during or following platinum-based therapy at 70 international sites between May 2014 and November 2014. Key inclusion criteria included age ≥18 yr, creatinine clearance ≥30 ml/min, and Eastern Cooperative Oncology Group performance status 0–1, with no limit on prior lines of treatment. Intervention: Patients in this cohort received atezolizumab 1200 mg intravenously every 3 wk until loss of clinical benefit. Outcome measurements and statistical analysis: Centrally assessed Response Evaluation Criteria In Solid Tumors v1.1 objective response rate (ORR), median duration of response, overall survival (OS), and adverse events were evaluated by prior treatment. Potential differences between subgroups were evaluated using log-rank (for OS) and chi-square (for ORR and adverse events frequencies) testing. Results and limitations: Three hundred and ten patients were efficacy and safety evaluable (median follow-up, 21 mo). Objective responses and prolonged OS occurred across all prespecified subgroups; median duration of response was not reached in most subgroups. In patients without prior systemic mUC therapy (first-line subgroup), ORR was 25% (95% confidence interval: 14–38), and median OS was 9.6 mo (95% confidence interval: 5.9–15.8). No significant differences in efficacy or toxicity by therapy line were observed. Conclusions: Atezolizumab demonstrated comparable efficacy and safety in previously treated patients with mUC across all lines of therapy evaluated. Patient summary: We investigated effects of previous treatment in patients with metastatic urothelial carcinoma that progressed after platinum-based therapy. Atezolizumab was active and tolerable no matter how many treatment regimens patients had received. ClinicalTrials.gov, NCT02108652. Outcomes by prior regimens were examined in a phase 2 atezolizumab study in platinum-treated urothelial carcinoma. Atezolizumab demonstrated comparable efficacy and safety in previously treated patients with metastatic urothelial carcinoma across all lines of therapy evaluated.
KW - Atezolizumab
KW - Immunotherapy
KW - Number of prior regimens
KW - Previous platinum-based chemotherapy
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85038904617&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2017.11.023
DO - 10.1016/j.eururo.2017.11.023
M3 - Article
C2 - 29273410
AN - SCOPUS:85038904617
SN - 0302-2838
VL - 73
SP - 462
EP - 468
JO - European Urology
JF - European Urology
IS - 3
ER -