Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study
| Autor: | Yohann Loriot, Nicholas J. Vogelzang, Constanze Kaiser, Rafael Morales-Barrera, Thomas Powles, Joseph Kim, Daniel P. Petrylak, Howard A. Burris, Marcella Fassò, Beiying Ding, Carol O'Hear, Joaquim Bellmunt, Fadi Braiteh |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research medicine.medical_specialty Metastatic Urothelial Carcinoma Time Factors Drug-Related Side Effects and Adverse Reactions Population Antibodies Monoclonal Humanized Cohort Studies 03 medical and health sciences 0302 clinical medicine Atezolizumab Internal medicine Carcinoma medicine Humans Neoplasm Metastasis education Adverse effect Survival analysis Original Investigation Aged Aged 80 and over education.field_of_study Carcinoma Transitional Cell Dose-Response Relationship Drug business.industry Antibodies Monoclonal Middle Aged medicine.disease Survival Analysis 030104 developmental biology Oncology Urinary Bladder Neoplasms Response Evaluation Criteria in Solid Tumors 030220 oncology & carcinogenesis Female Urothelium business Cohort study Follow-Up Studies |
| Popis: | Importance Atezolizumab (anti–programmed death ligand 1) has demonstrated safety and activity in advanced and metastatic urothelial carcinoma, but its long-term clinical profile remains unknown. Objective To report long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma. Design, Setting, and Participants Patients were enrolled in an expansion cohort of an ongoing, open-label, phase 1 study. Median follow-up was 37.8 months (range, >0.7 to 44.4 months). Enrollment occurred between March 2013 and August 2015 at US and European academic medical centers. Eligible patients had measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Eastern Cooperative Oncology Group performance status 0 to 1, and a representative tumor sample. Programmed death ligand 1 expression on immune cells was assessed (VENTANA SP142 assay). Interventions Atezolizumab was given intravenously every 3 weeks until unacceptable toxic effects, protocol nonadherence, or loss of clinical benefit. Main Outcomes and Measures Primary outcome was safety. Secondary outcomes included objective response rate, duration of response, and progression-free survival. Response and overall survival were assessed in key baseline subgroups. Results Ninety-five patients were evaluable (72 [76%] male; median age, 66 years [range, 36-89 years]). Forty-five (47%) received atezolizumab as third-line therapy or greater. Nine patients (9%) had a grade 3 to 4 treatment-related adverse event, mostly within the first treatment year; no serious related adverse events were observed thereafter. One patient (1%) discontinued treatment due to a related event. No treatment-related deaths occurred. Responses occurred in 26% (95% CI, 18%-36%) of patients. Median duration of response was 22.1 months (range, 2.8 to >41.0 months), and median progression-free survival was 2.7 months (95% CI, 1.4-4.3 months). Median overall survival was 10.1 months (95% CI, 7.3-17.0 months); 3-year OS rate was 27% (95% CI, 17%-36%). Response occurred in 40% (95% CI, 26%-55%; n = 40) and 11% (95% CI, 4%-25%; n = 44) of patients with programmed death ligand 1 expression of at least 5% tumor-infiltrating immune cells (IC2/3) or less than 5% (IC0/1), respectively. Median overall survival in patients with IC2/3 and IC0/1 was 14.6 months (95% CI, 9.0 months to not estimable) and 7.6 months (95% CI, 4.7 to 13.9 months), respectively. Conclusions and Relevance Atezolizumab remained well tolerated and provided durable clinical benefit to a heavily pretreated metastatic urothelial carcinoma population in this long-term study. Trial Registration clinicaltrials.gov Identifier:NCT01375842 |
| Databáze: | OpenAIRE |
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