METHODS: In this multicentre, phase 2, single-arm study, patients aged 18 years or older with metastatic or surgically unresectable locally advanced urothelial carcinoma, measurable disease (according to Response Evaluation Criteria In Solid Tumors v1.1), Eastern Cooperative Oncology Group performance statuses of 0 or 1, and available tumour samples for biomarker analysis received nivolumab 3 mg/kg intravenously every 2 weeks until disease progression and clinical deterioration, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was overall objective response confirmed by the blinded independent review committee in all treated patients and by tumour PD-L1 expression (≥5% and ≥1%). This trial is registered with ClinicalTrials.gov, number NCT02387996, and is completed. Follow-up is still ongoing.
FINDINGS: Between March 9, 2015, and Oct 16, 2015, 270 patients from 63 sites in 11 countries received nivolumab, and 265 were evaluated for activity. Median follow-up for overall survival was 7·00 months (IQR 2·96–8·77). Confirmed objective response was achieved in 52 (19·6%, 95% CI 15·0–24·9) of 265 patients. Confirmed objective response was achieved in 23 (28·4%, 95% CI 18·9–39·5) of the 81 patients with PD-L1 expression of 5% or greater, 29 (23·8%, 95% CI 16·5–32·3) of the 122 patients with PD-L1 expression of 1% or greater, and 23 (16·1%, 95% CI 10·5–23·1) of the 143 patients with PD-L1 expression of less than 1%. Grade 3–4 treatment-related adverse events occurred in 48 (18%) of 270 patients—most commonly grade 3 fatigue and diarrhea, which each occurred in five patients. Three deaths were attributed to treatment (pneumonitis, acute respiratory failure, and cardiovascular failure).
INTERPRETATION: Nivolumab monotherapy provided meaningful clinical benefit, irrespective of PD-L1 expression, and was associated with an acceptable safety profile in previously treated patients with metastatic or surgically unresectable urothelial carcinoma.
FUNDINGS: Bristol-Myers Squibb.
LANCET. 2017 January 25 [Epub ahead of print]
Padmanee Sharma, MD,1,2 Margitta Retz, MD,3 Arlene Siefker-Radtke, MD,1 Ari Baron, MD,4 Andrea Necchi, MD,5 Jens Bedke, MD,6 Elizabeth R Plimack, MD,7 Daniel Vaena, MD,8 Marc-Oliver Grimm, MD,9 Sergio Bracarda, MD,10 José Ángel Arranz, MD,11 Sumanta Pal, MD,12 Chikara Ohyama, MD,13 Abdel Saci, PhD,14 Xiaotao Qu, PhD,15 Alexandre Lambert, PhD,16 Suba Krishnan, MD,17 Alex Azrilevich, PharmD,17 Matthew D Galsky, MD18
1. Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas
2. Department of Immunology, MD Anderson Cancer Center, University of Texas, Houston, Texas
3. Department of Urology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
4. Department of Medicine, California Pacific Medical Center, San Francisco, California
5. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
6. Department of Urology, University of Tübingen, Tübingen, Germany
7. Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
8. Division of Hematology, Oncology, and Bone Marrow Transplantation/Department of Medicine and Urology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa
9. Department of Urology, Jena University Hospital, Jena, Germany
10. Department of Oncology and Medical Oncology Unit, Ospedale San Donato, Azienda USL Toscana Sud-Est, Istituto Toscano Tumori, Arezzo, Italy
11. Genitourinary and Gynecologic Section, Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
12. Kidney Cancer Program, City of Hope Comprehensive Cancer Center, Duarte, California
13. Department of Urology, Hirosaki University, Hirosaki, Aomori, Japan
14. Exploratory Clinical & Translational Research Department, Bristol-Myers Squibb, Princeton, New Jersey
15. Translational Bioinformatics Department, Bristol-Myers Squibb, Princeton, New Jersey
16. Biometrics Department, Bristol-Myers Squibb, Braine-l'Alleud, Belgium
17. Global Clinical Research Oncology Department, Bristol-Myers Squibb, Princeton, New Jersey
18. Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai/Tisch Cancer Institute, New York, New York
The Lancet volume18, issue 3, P312-322, March 01, 2017, DOI:https://doi.org/10.1016/S1470-2045(17)30065-7