Safety and efficacy of durvalumab (MEDI4736), an anti–programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer
Open accessAbstract
PURPOSE: To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). METHODS: A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1-positive as ≥ 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1. RESULTS: A total of 61 patients (40 PD-L1-positive, 21 PD-L1-negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1-positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1-negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks). CONCLUSION: Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, many of whom were heavily pretreated.
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Durvalumab was approved by the FDA in May 2017 for the treatment of patients with urothelial carcinoma (metastatic or locally advanced) who progressed during or after platinum-based chemotherapy, including those who had disease progression within one year of treatment with a platinum-based regimen in the neoadjuvant or adjuvant setting followed by surgical resection.
“Durvalumab was also approved by the FDA in May 2017 for the treatment of patients with urothelial carcinoma (metastatic or locally advanced) who progressed during or after platinum-based chemotherapy, including those who had disease progression within one year of treatment with a platinum-based regimen in the neoadjuvant or adjuvant setting followed by surgical resection [70].”
From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [70]
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Cites
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1992) · Springer series in statistics · doi:10.1007/978-1-4612-4380-9_25 · Cited by 45,232 · see citing works
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1958) · Journal of the American Statistical Association · doi:10.1080/01621459.1958.10501452 · Cited by 39,158 · see citing works
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534 · see citing works
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,314 · see citing works
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838 · see citing works
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335 · see citing works
PD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378 · see citing works
Rosenberg, J. E., Hoffman-Censits, J., Powles, T., van der Heijden, M. S., Balar, A. V., Necchi, A., Dawson, N., O'Donnell, P. H., Balmanoukian, A., Loriot, Y., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00561-4 · Cited by 3,669 · see citing works
Self-citationImmune Checkpoint Blockade in Cancer Therapy
Postow, M. A., Callahan, M. K., & Wolchok, J. D. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.4358 · Cited by 2,736 · see citing works
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer
Powles, T. B., Eder, J. P., Fine, G. D., Braiteh, F. S., Loriot, Y., Cruz, C., Joaquim Bellmunt, B., Burris, H. A., Petrylak, D. P., Teng, S.-L. M., et al. (2014) · Nature · doi:10.1038/nature13904 · Cited by 2,383 · see citing works
The PD‐1 pathway in tolerance and autoimmunity
Francisco, L. M., Sage, P. T., & Sharpe, A. H. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00923.x · Cited by 2,300 · see citing works
von der Maase, H., Hansen, S. W., Roberts, J. T., Dogliotti, L., Oliver, R. T. D., Moore, M. J., Bodrogi, I., Albers, P., Knuth, A. K., Lippert, C. M., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.17.3068 · Cited by 2,283 · see citing works
von der Maase, H., Sengeløv, L., Roberts, J. T., Ricci, S., Dogliotti, L., Oliver, R. T. D., Moore, M. J., Zimmermann, A. H., & Arning, M. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.07.757 · Cited by 1,850 · see citing works
Inhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608 · see citing works
Rizvi, N. A., Mazières, J., Planchard, D., Stinchcombe, T. E., Dy, G. K., Antonia, S. J., Horn, L., Lena, H., Minenza, E., Mennecier, B., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70054-9 · Cited by 1,415 · see citing works
Self-citationHamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K., Minato, N., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611533104 · Cited by 1,378 · see citing works
Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology
von Mehren, M., Kane, J. M., Agulnik, M., Bui, M. M., Carr, J. R., Choy, E., Connelly, M., Dry, S., Ganjoo, K. N., González, R., et al. (2022) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2022.0035 · Cited by 1,190 · see citing works
Joaquim Bellmunt, B., Théodore, C., Demkov, T., Komyakov, B. K., Sengeløv, L., Daugaard, G., Caty, A., Carles, J., Jagiełło-Gruszfeld, A., Karyakin, O., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.5534 · Cited by 766 · see citing works
Toxicities of Immunotherapy for the Practitioner
Weber, J. S., Yang, J. C., Atkins, M. B., & Disis, M. L. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.60.0379 · Cited by 652 · see citing works
Sternberg, C. N., de Mulder, P., Schornagel, J. H., et al. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.08.032 · Cited by 542 · see citing works
Plimack, E. R., Dunbrack, R. L., Brennan, T. A., Andrake, M., Zhou, Y., Serebriiskii, I. G., Slifker, M. J., Alpaugh, K. R., Dulaimi, E., Palma, N. A., et al. (2015) · European Urology · doi:10.1016/j.eururo.2015.07.009 · Cited by 521 · see citing works
Smoking cessation, version 1.2016, NCCN clinical practice guidelines in oncology
Shields, P. G., Herbst, R. S., Arenberg, D., Benowitz, N. L., Bierut, L., Luckart, J. B., Cinciripini, P., Collins, B., David, S., Davis, J., et al. (2016) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2016.0152 · Cited by 146 · see citing works
A phase 1 study of MEDI4736, an anti–PD-L1 antibody, in patients with advanced solid tumors.
Lutzky, J., Antonia, S. J., Blake-Haskins, A., Li, X., Robbins, P. B., Shalabi, A. M., Vasselli, J., Ibrahim, R. A., Khleif, S. N., & Segal, N. H. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.3001 · Cited by 105 · see citing works
Self-citationNew Strategies in Bladder Cancer: A Second Coming for Immunotherapy
Ghasemzadeh, A., Bivalacqua, T. J., Hahn, N. M., & Drake, C. G. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1135 · Cited by 93 · see citing works
Current Perspectives in Immunotherapy for Non-Small Cell Lung Cancer
Garon, E. B. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.09.019 · Cited by 57 · see citing works
Segal, N. H., Hamid, O., Hwu, W., Massard, C., Butler, M. O., Antonia, S. J., Blake-Haskins, A., Robbins, P. B., Li, X., Vasselli, J., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu342.11 · Cited by 56 · see citing works
Self-citationFury, M. G., Ou, S. I., Balmanoukian, A. S., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu340.3 · Cited by 31 · see citing works
Rebelatto, M. C., Mistry, A., Sabalos, C., Walker, J., Midha, A., Steele, K. E., Robbins, P. B., Li, X., Shi, L., Blake-Haskins, J. A., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.8033 · Cited by 29 · see citing works
Self-citationThe development of immunotherapy in urothelial bladder cancer
Powles, T. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.51 · Cited by 9 · see citing works
Immunotherapy for Non-Small-Cell Lung Cancer: The Past 10 Years
Vansteenkiste, J., Craps, J., Brucker, N. D., & Wauters, I. (2015) · Future Oncology · doi:10.2217/fon.15.116 · Cited by 7 · see citing works
Immunotherapy for Bladder Cancer: Changing the Landscape
Malik, L. (2014) · Cancer and Clinical Oncology · doi:10.5539/cco.v3n2p36 · Cited by 3 · see citing works
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Bellmunt, J., de Wit, R., Vaughn, D. J., Fradet, Y., Lee, J.-L., Fong, L., Vogelzang, N. J., Climent, M. A., Petrylak, D. P., Choueiri, T. K., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1613683 · Cited by 3,395 · see citing works
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Hegde, P. S., & Chen, D. S. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.011 · Cited by 2,238 · see citing works
Powles, T., Durán, I., van der Heijden, M. S., Loriot, Y., Vogelzang, N. J., De Giorgi, U., Oudard, S., Retz, M. M., Castellano, D., Bamias, A., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(17)33297-x · Cited by 1,408 · see citing works
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Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini-Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022) · Current Oncology · doi:10.3390/curroncol29050247 · Cited by 1,353 · see citing works
Powles, T., O'Donnell, P. H., Massard, C., Arkenau, H.-T., Friedlander, T. W., Hoimes, C. J., Lee, J. L., Ong, M., Sridhar, S. S., Vogelzang, N. J., et al. (2017) · JAMA Oncology · doi:10.1001/jamaoncol.2017.2411 · Cited by 869 · see citing works
Self-citationApolo, A. B., Infante, J. R., Balmanoukian, A., Patel, M. R., Wang, D., Kelly, K., Mega, A. E., Britten, C. D., Ravaud, A., Mita, A. C., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.6795 · Cited by 585 · see citing works
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Abdel-Wahab, N., Shah, M., Lopez-Olivo, M. A., & Suarez-Almazor, M. E. (2018) · Annals of Internal Medicine · doi:10.7326/m17-2073 · Cited by 487 · see citing works
Strauss, J., Heery, C. R., Schlom, J., Madan, R. A., Cao, L., Kang, Z., Lamping, E., Marté, J. L., Donahue, R. N., Grenga, I., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2653 · Cited by 406 · see citing works
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Constantinidou, A., Alifieris, C., & Trafalis, D. T. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.09.008 · Cited by 342 · see citing works
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Abdel-Wahab, N., Safa, H., Abudayyeh, A., Johnson, D. H., Trinh, V. A., Zobniw, C. M., Lin, H., Wong, M. K., Abdelrahim, M., Gaber, A. O., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0585-1 · Cited by 294 · see citing works
Karachaliou, N., Gonzalez-Cao, M., Crespo, G., Drozdowskyj, A., Aldeguer, E., Gimenez-Capitan, A., Teixido, C., Molina-Vila, M. A., Viteri, S., De Los Llanos Gil, M., et al. (2018) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834017749748 · Cited by 285 · see citing works
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- Authors
- Massard, C., Gordon, M. S., Sharma, S., Rafii, S., Wainberg, Z. A., Luke, J., Curiel, T. J., Colon-Otero, G., Hamid, O., Sanborn, R. E., O’Donnell, P. H., Drakaki, A., Tan, W., Kurland, J. F., Rebelatto, M. C., Jin, X., Blake-Haskins, J. A., Gupta, A., & Segal, N. H.
- Affiliations
- University of California, Los Angeles (US)
- Christophe Massard, Institut Gustave Roussy Cancer Centre, Villejuif, France; Michael S. Gordon, Pinnacle Oncology Hematology, Scottsdale, AZ; Sunil Sharma, Huntsman Cancer Institute, Salt Lake City, UT; Saeed Rafii, Sarah Cannon Research Institute, London, UK; Zev A. Wainberg and Alexandra Drakaki, University of California, Los Angeles; and Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles, CA; Jason Luke and Peter H. O’Donnell, University of Chicago Comprehensive Cancer Center, Chicago...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2016-09-10
- Volume
- 34
- Issue
- 26
- Pages
- 3119-3125
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC5569690
- OpenAlex
- W2414977199
- Cited by
- 840
- References
- 33
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 33 · 2023: 52 · 2022: 77 · 2021: 100 · 2020: 113 · 2019: 110 · 2018: 152 · 2017: 148 · 2016: 23 · 2013: 1
- FWCI
- 77.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- durvalumab, bladder urothelial carcinoma, PD-L1 expression, immune checkpoint inhibitors, objective response rate, treatment safety, adverse events, metastatic solid tumors, predictive biomarkers, immune checkpoint blockade, acute kidney injury, fatigue, diarrhea, duration of response, treatment-related adverse events
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Biopsy, Urinary Bladder Neoplasms, Female, Humans, Immunohistochemistry, Male, Middle Aged, Time Factors, Treatment Outcome, Urothelium, B7-H1 Antigen
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