Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: A single-arm, multicentre, phase 2 trial Journal Article
| Authors: | Balar, A. V.; Galsky, M. D.; Rosenberg, J. E.; Powles, T.; Petrylak, D. P.; Bellmunt, J.; Loriot, Y.; Necchi, A.; Hoffman-Censits, J.; Perez-Gracia, J. L.; Dawson, N. A.; van der Heijden, M. S.; Dreicer, R.; Srinivas, S.; Retz, M. M.; Joseph, R. W.; Drakaki, A.; Vaishampayan, U. N.; Sridhar, S. S.; Quinn, D. I.; Durán, I.; Shaffer, D. R.; Eigl, B. J.; Grivas, P. D.; Yu, E. Y.; Li, S.; Kadel, E. E. 3rd; Boyd, Z.; Bourgon, R.; Hegde, P. S.; Mariathasan, S.; Thåström, A.; Abidoye, O. O.; Fine, G. D.; Bajorin, D. F.; for the IMvigor210 Study Group |
| Article Title: | Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: A single-arm, multicentre, phase 2 trial |
| Abstract: | Background First-line chemotherapy for patients with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma is associated with short response duration, poor survival, and high toxicity. This study assessed atezolizumab (anti-programmed death-ligand 1 [PD-L1]) as treatment for metastatic urothelial cancer in cisplatin-ineligible patients. Methods For this single-arm, multicentre, phase 2 study, in 47 academic medical centres and community oncology practices in seven countries in North America and Europe, we recruited previously untreated patients with locally advanced or metastatic urothelial cancer who were cisplatin ineligible. Patients were given 1200 mg intravenous atezolizumab every 21 days until progression. The primary endpoint was independently confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 (central review), assessed in prespecified subgroups based on PD-L1 expression and in all patients. All participants who received one or more doses of atezolizumab were included in the primary and safety analyses. This study was registered with ClinicalTrials.gov, number NCT02108652. Findings Between June 9, 2014, and March 30, 2015, we enrolled 123 patients, of whom 119 received one or more doses of atezolizumab. At 17·2 months' median follow-up, the objective response rate was 23% (95% CI 16 to 31), the complete response rate was 9% (n=11), and 19 of 27 responses were ongoing. Median response duration was not reached. Responses occurred across all PD-L1 and poor prognostic factor subgroups. Median progression-free survival was 2·7 months (2·1 to 4·2). Median overall survival was 15·9 months (10·4 to not estimable). Tumour mutation load was associated with response. Treatment-related adverse events that occurred in 10% or more of patients were fatigue (36 [30%] patients), diarrhoea (14 [12%] patients), and pruritus (13 [11%] patients). One treatment-related death (sepsis) occurred. Nine (8%) patients had an adverse event leading to treatment discontinuation. Immune-mediated events occurred in 14 (12%) patients. Interpretation Atezolizumab showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated metastatic urothelial cancer. Funding F Hoffmann-La Roche, Genentech. © 2017 Elsevier Ltd |
| Keywords: | adult; cancer survival; treatment response; aged; primary tumor; major clinical study; fatigue; cisplatin; advanced cancer; cancer combination chemotherapy; diarrhea; drug safety; drug withdrawal; hypophosphatemia; treatment duration; gemcitabine; cancer adjuvant therapy; cancer patient; follow up; carboplatin; cancer immunotherapy; progression free survival; phase 2 clinical trial; anemia; nausea; thrombocytopenia; vomiting; kidney failure; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; asthenia; backache; chill; dyspnea; fever; pruritus; rash; europe; alanine aminotransferase; aspartate aminotransferase; bilirubin; drug fatality; hypotension; maculopapular rash; multicenter study; acne; xerostomia; sepsis; colitis; liver disease; flu like syndrome; dermatitis; headache; hypothyroidism; corticosteroid; autoimmune disease; portal vein thrombosis; muscle spasm; transitional cell carcinoma; bilirubin blood level; immunopathology; lymphocyte count; north america; multiple organ failure; decreased appetite; hypersensitivity; corticosteroid therapy; cancer prognosis; response evaluation criteria in solid tumors; infusion related reaction; very elderly; human; male; female; priority journal; article; atezolizumab; mutational load |
| Journal Title: | Lancet |
| Volume: | 389 |
| Issue: | 10064 |
| ISSN: | 0140-6736 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2017-01-07 |
| Start Page: | 67 |
| End Page: | 76 |
| Language: | English |
| DOI: | 10.1016/s0140-6736(16)32455-2 |
| PROVIDER: | scopus |
| PUBMED: | 27939400 |
| PMCID: | PMC5568632 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 February 2017 -- Source: Scopus |
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