Biomarkers for immunotherapy in bladder cancer: a moving target
Abstract Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting th...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2017-11-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40425-017-0299-1 |
| _version_ | 1828492115466780672 |
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| author | David H. Aggen Charles G. Drake |
| author_facet | David H. Aggen Charles G. Drake |
| author_sort | David H. Aggen |
| collection | DOAJ |
| description | Abstract Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U.S. Food and Drug Administration (FDA). The PD-1 antibody nivolumab also demonstrated an overall survival benefit, in this case in comparison to historical controls. Similarly, antibodies targeting PD-L1 including atezolizumab, durvalumab, and avelumab have now received accelerated approval from the FDA as second line treatments for mUC, with durable response lasting more than 1 year in some patients. Some of these agents are approved in the first line setting as well - based on single-arm phase II studies atezolizumab and pembrolizumab received accelerated approval for first-line treatment of cisplatin ineligible patients. Despite these multiple approvals, the development of clinically useful biomarkers to determine the optimal treatment for patients remains somewhat elusive. In this review, we examine key clinical trial results with anti-PD1/PD-L1 antibodies and discuss progress towards developing novel biomarkers beyond PD-L1 expression. |
| first_indexed | 2024-12-11T11:14:52Z |
| format | Article |
| id | doaj.art-d6833af2c3904f7abc2104daa6822f96 |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-12-11T11:14:52Z |
| publishDate | 2017-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-d6833af2c3904f7abc2104daa6822f962022-12-22T01:09:22ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262017-11-015111310.1186/s40425-017-0299-1Biomarkers for immunotherapy in bladder cancer: a moving targetDavid H. Aggen0Charles G. Drake1New York-Presbyterian/Columbia University Medical Center, Hematology/OncologyNew York-Presbyterian/Columbia University Medical Center, Hematology/OncologyAbstract Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U.S. Food and Drug Administration (FDA). The PD-1 antibody nivolumab also demonstrated an overall survival benefit, in this case in comparison to historical controls. Similarly, antibodies targeting PD-L1 including atezolizumab, durvalumab, and avelumab have now received accelerated approval from the FDA as second line treatments for mUC, with durable response lasting more than 1 year in some patients. Some of these agents are approved in the first line setting as well - based on single-arm phase II studies atezolizumab and pembrolizumab received accelerated approval for first-line treatment of cisplatin ineligible patients. Despite these multiple approvals, the development of clinically useful biomarkers to determine the optimal treatment for patients remains somewhat elusive. In this review, we examine key clinical trial results with anti-PD1/PD-L1 antibodies and discuss progress towards developing novel biomarkers beyond PD-L1 expression.http://link.springer.com/article/10.1186/s40425-017-0299-1Bladder cancerPD-1Pd-L1ImmunotherapyAtezolizumabNivolumab |
| spellingShingle | David H. Aggen Charles G. Drake Biomarkers for immunotherapy in bladder cancer: a moving target Journal for ImmunoTherapy of Cancer Bladder cancer PD-1 Pd-L1 Immunotherapy Atezolizumab Nivolumab |
| title | Biomarkers for immunotherapy in bladder cancer: a moving target |
| title_full | Biomarkers for immunotherapy in bladder cancer: a moving target |
| title_fullStr | Biomarkers for immunotherapy in bladder cancer: a moving target |
| title_full_unstemmed | Biomarkers for immunotherapy in bladder cancer: a moving target |
| title_short | Biomarkers for immunotherapy in bladder cancer: a moving target |
| title_sort | biomarkers for immunotherapy in bladder cancer a moving target |
| topic | Bladder cancer PD-1 Pd-L1 Immunotherapy Atezolizumab Nivolumab |
| url | http://link.springer.com/article/10.1186/s40425-017-0299-1 |
| work_keys_str_mv | AT davidhaggen biomarkersforimmunotherapyinbladdercanceramovingtarget AT charlesgdrake biomarkersforimmunotherapyinbladdercanceramovingtarget |