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Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Open accessAbstract
BACKGROUND: Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS: In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS: As of February 24, 2012, a total of 207 patients--75 with non-small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer--had received anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS: Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.).
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“For example, it is now evident that simply combining two “off the shelf” immune checkpoint inhibitors to enhance effector T cell function – a strategy that has worked in several other solid cancers – has minimal to no impact in a disease where a multiplicity of immune defects co-exist283,284.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [283]
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“A promising aspect is that clinical blockade of B7-H1/PD-1, the key T cell exhaustion pathway, may rescue T cell effector functions in vivo, and results in significant objective clinical responses [32,33].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [32]
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Metadata
- Authors
- Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., Pitot, H. C., Hamid, O., Bhatia, S., Martins, R., Eaton, K., Chen, S., Salay, T. M., Alaparthy, S., Grosso, J. F., Korman, A. J., Parker, S. M., Agrawal, S., Goldberg, S. M., Pardoll, D. M., Gupta, A., & Wigginton, J. M.
- Affiliations
- Johns Hopkins University (US)
- Seattle Cancer Care Alliance (US)
- The University of Texas MD Anderson Cancer Center (US)
- Baylor St. Luke's Medical Center (US)
- Winship Cancer Institute (US)
- Roswell Park Comprehensive Cancer Center (US)
- Mayo Clinic (US)
- Bristol-Myers Squibb (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2012-06-28
- Volume
- 366
- Issue
- 26
- Pages
- 2455-2465
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3563263
- OpenAlex
- W2101653483
- Cited by
- 7,945
- References
- 39
- Citations by year
- 2026: 178 · 2025: 315 · 2024: 418 · 2023: 533 · 2022: 566 · 2021: 611 · 2020: 694 · 2019: 629 · 2018: 592 · 2017: 733 · 2016: 723 · 2015: 762 · 2014: 573 · 2013: 493 · 2012: 108
- FWCI
- 306.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- National Cancer Institute (U10CA180802, P30CA015704, R01CA142779, P30CA006973)
- National Center for Research Resources (UL1RR024148)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- PD-L1 inhibitors, PD-L1 blockade, PD-1/PD-L1 axis, immune checkpoint inhibitors, advanced cancer, non-small cell lung cancer, melanoma, renal cell carcinoma, ovarian cancer, treatment safety, objective response rate, antitumor immunity
- MeSH terms
- Nivolumab, Adult, Antibodies, Monoclonal, Antineoplastic Agents, Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Dose-Response Relationship, Drug, Female, Humans, Male, Melanoma, Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms, Colorectal Neoplasms, Programmed Cell Death 1 Receptor
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