Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study
PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit. We aimed to assess the safety and activity of an anti-PD-1 antibody pembrolizumab in patients with locally advanced or metastatic urothelial cancer. This study w...
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| Published in | The lancet oncology Vol. 18; no. 2; pp. 212 - 220 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
01.02.2017
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1470-2045 1474-5488 |
| DOI | 10.1016/S1470-2045(17)30007-4 |
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| Abstract | PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit. We aimed to assess the safety and activity of an anti-PD-1 antibody pembrolizumab in patients with locally advanced or metastatic urothelial cancer.
This study was part of the non-randomised, multi-cohort, open-label, phase 1b KEYNOTE-012 basket trial. We enrolled patients aged 18 years and older with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic urothelial cancer, including cancers of the renal pelvis, ureter, bladder, or urethra, from eight hospitals in the USA and Israel. Patients were required to have at least 1% PD-L1 expression detected on the tumour cells or in tumour stroma, as determined by immunohistochemistry. Patients were given 10 mg/kg intravenous pembrolizumab every 2 weeks until disease progression, unacceptable toxic effects, or the end of the study (ie, 24 months of treatment). Primary endpoints were safety and overall response (defined by Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1), as assessed by a masked, independent central review. Safety was assessed in patients who received one or more doses of pembrolizumab (all-patients-as-treated population); activity was assessed in patients who received pembrolizumab, had measurable disease at baseline, and had one or more post-baseline scans, or discontinued because of progressive disease or treatment-related adverse events (full analysis set). This study is registered with ClinicalTrials.gov, number NCT01848834, and is no longer enrolling patients; follow-up is ongoing.
Between May 14, 2013, and Dec 10, 2013, 115 patients were tissue pre-screened as part of a two-part consent process. 61 (53%) patients were PD-L1 positive, of whom 33 were enrolled in this study. All enrolled patients received at least one dose of pembrolizumab and were included in the safety analyses. 27 patients comprised the full analysis set and were deemed assessable for activity. Six patients were not assessable: three discontinued study drug because of a non-treatment-related adverse event before the first post-baseline scan, two withdrew before the first post-baseline scan, and one had no measurable disease at baseline. The most common treatment-related adverse events were fatigue (six [18%] of 33 patients) and peripheral oedema (4 [12%]). Five (15%) patients had 11 grade 3 treatment-related adverse events; no single event occurred in more than one patient. Three (9%) patients experienced five serious treatment-related adverse events. After median follow-up of 13 months (range 1–26, IQR 5–23), an overall response was achieved in seven (26% [95% CI 11–46]) of 27 assessable patients, with three (11% [2–29]) complete and four (15% [4–34]) partial responses. Of the four deaths that occurred during the study (cardiac arrest, pneumonia, sepsis, and subarachnoid haemorrhage), none were deemed treatment related.
Pembrolizumab showed anti-tumour activity and acceptable safety in patients with advanced urothelial cancer, supporting ongoing phase 2 and 3 studies of pembrolizumab in this population.
Merck & Co., Inc. |
|---|---|
| AbstractList | PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit. We aimed to assess the safety and activity of an anti-PD-1 antibody pembrolizumab in patients with locally advanced or metastatic urothelial cancer.
This study was part of the non-randomised, multi-cohort, open-label, phase 1b KEYNOTE-012 basket trial. We enrolled patients aged 18 years and older with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic urothelial cancer, including cancers of the renal pelvis, ureter, bladder, or urethra, from eight hospitals in the USA and Israel. Patients were required to have at least 1% PD-L1 expression detected on the tumour cells or in tumour stroma, as determined by immunohistochemistry. Patients were given 10 mg/kg intravenous pembrolizumab every 2 weeks until disease progression, unacceptable toxic effects, or the end of the study (ie, 24 months of treatment). Primary endpoints were safety and overall response (defined by Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1), as assessed by a masked, independent central review. Safety was assessed in patients who received one or more doses of pembrolizumab (all-patients-as-treated population); activity was assessed in patients who received pembrolizumab, had measurable disease at baseline, and had one or more post-baseline scans, or discontinued because of progressive disease or treatment-related adverse events (full analysis set). This study is registered with ClinicalTrials.gov, number NCT01848834, and is no longer enrolling patients; follow-up is ongoing.
Between May 14, 2013, and Dec 10, 2013, 115 patients were tissue pre-screened as part of a two-part consent process. 61 (53%) patients were PD-L1 positive, of whom 33 were enrolled in this study. All enrolled patients received at least one dose of pembrolizumab and were included in the safety analyses. 27 patients comprised the full analysis set and were deemed assessable for activity. Six patients were not assessable: three discontinued study drug because of a non-treatment-related adverse event before the first post-baseline scan, two withdrew before the first post-baseline scan, and one had no measurable disease at baseline. The most common treatment-related adverse events were fatigue (six [18%] of 33 patients) and peripheral oedema (4 [12%]). Five (15%) patients had 11 grade 3 treatment-related adverse events; no single event occurred in more than one patient. Three (9%) patients experienced five serious treatment-related adverse events. After median follow-up of 13 months (range 1–26, IQR 5–23), an overall response was achieved in seven (26% [95% CI 11–46]) of 27 assessable patients, with three (11% [2–29]) complete and four (15% [4–34]) partial responses. Of the four deaths that occurred during the study (cardiac arrest, pneumonia, sepsis, and subarachnoid haemorrhage), none were deemed treatment related.
Pembrolizumab showed anti-tumour activity and acceptable safety in patients with advanced urothelial cancer, supporting ongoing phase 2 and 3 studies of pembrolizumab in this population.
Merck & Co., Inc. PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit. We aimed to assess the safety and activity of an anti-PD-1 antibody pembrolizumab in patients with locally advanced or metastatic urothelial cancer. Methods This study was part of the non-randomised, multi-cohort, open-label, phase 1b KEYNOTE-012 basket trial. We enrolled patients aged 18 years and older with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic urothelial cancer, including cancers of the renal pelvis, ureter, bladder, or urethra, from eight hospitals in the USA and Israel. Patients were required to have at least 1% PD-L1 expression detected on the tumour cells or in tumour stroma, as determined by immunohistochemistry. Patients were given 10 mg/kg intravenous pembrolizumab every 2 weeks until disease progression, unacceptable toxic effects, or the end of the study (ie, 24 months of treatment). Primary endpoints were safety and overall response (defined by Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1), as assessed by a masked, independent central review. Safety was assessed in patients who received one or more doses of pembrolizumab (all-patients-as-treated population); activity was assessed in patients who received pembrolizumab, had measurable disease at baseline, and had one or more post-baseline scans, or discontinued because of progressive disease or treatment-related adverse events (full analysis set). This study is registered withClinicalTrials.gov, numberNCT01848834, and is no longer enrolling patients; follow-up is ongoing. Findings Between May 14, 2013, and Dec 10, 2013, 115 patients were tissue pre-screened as part of a two-part consent process. 61 (53%) patients were PD-L1 positive, of whom 33 were enrolled in this study. All enrolled patients received at least one dose of pembrolizumab and were included in the safety analyses. 27 patients comprised the full analysis set and were deemed assessable for activity. Six patients were not assessable: three discontinued study drug because of a non-treatment-related adverse event before the first post-baseline scan, two withdrew before the first post-baseline scan, and one had no measurable disease at baseline. The most common treatment-related adverse events were fatigue (six [18%] of 33 patients) and peripheral oedema (4 [12%]). Five (15%) patients had 11 grade 3 treatment-related adverse events; no single event occurred in more than one patient. Three (9%) patients experienced five serious treatment-related adverse events. After median follow-up of 13 months (range 1-26, IQR 5-23), an overall response was achieved in seven (26% [95% CI 11-46]) of 27 assessable patients, with three (11% [2-29]) complete and four (15% [4-34]) partial responses. Of the four deaths that occurred during the study (cardiac arrest, pneumonia, sepsis, and subarachnoid haemorrhage), none were deemed treatment related. Interpretation Pembrolizumab showed anti-tumour activity and acceptable safety in patients with advanced urothelial cancer, supporting ongoing phase 2 and 3 studies of pembrolizumab in this population. Funding Merck & Co., Inc. Summary Background PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit. We aimed to assess the safety and activity of an anti-PD-1 antibody pembrolizumab in patients with locally advanced or metastatic urothelial cancer. Methods This study was part of the non-randomised, multi-cohort, open-label, phase 1b KEYNOTE-012 basket trial. We enrolled patients aged 18 years and older with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic urothelial cancer, including cancers of the renal pelvis, ureter, bladder, or urethra, from eight hospitals in the USA and Israel. Patients were required to have at least 1% PD-L1 expression detected on the tumour cells or in tumour stroma, as determined by immunohistochemistry. Patients were given 10 mg/kg intravenous pembrolizumab every 2 weeks until disease progression, unacceptable toxic effects, or the end of the study (ie, 24 months of treatment). Primary endpoints were safety and overall response (defined by Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1), as assessed by a masked, independent central review. Safety was assessed in patients who received one or more doses of pembrolizumab (all-patients-as-treated population); activity was assessed in patients who received pembrolizumab, had measurable disease at baseline, and had one or more post-baseline scans, or discontinued because of progressive disease or treatment-related adverse events (full analysis set). This study is registered with ClinicalTrials.gov , number NCT01848834 , and is no longer enrolling patients; follow-up is ongoing. Findings Between May 14, 2013, and Dec 10, 2013, 115 patients were tissue pre-screened as part of a two-part consent process. 61 (53%) patients were PD-L1 positive, of whom 33 were enrolled in this study. All enrolled patients received at least one dose of pembrolizumab and were included in the safety analyses. 27 patients comprised the full analysis set and were deemed assessable for activity. Six patients were not assessable: three discontinued study drug because of a non-treatment-related adverse event before the first post-baseline scan, two withdrew before the first post-baseline scan, and one had no measurable disease at baseline. The most common treatment-related adverse events were fatigue (six [18%] of 33 patients) and peripheral oedema (4 [12%]). Five (15%) patients had 11 grade 3 treatment-related adverse events; no single event occurred in more than one patient. Three (9%) patients experienced five serious treatment-related adverse events. After median follow-up of 13 months (range 1–26, IQR 5–23), an overall response was achieved in seven (26% [95% CI 11–46]) of 27 assessable patients, with three (11% [2–29]) complete and four (15% [4–34]) partial responses. Of the four deaths that occurred during the study (cardiac arrest, pneumonia, sepsis, and subarachnoid haemorrhage), none were deemed treatment related. Interpretation Pembrolizumab showed anti-tumour activity and acceptable safety in patients with advanced urothelial cancer, supporting ongoing phase 2 and 3 studies of pembrolizumab in this population. Funding Merck & Co., Inc. Background PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit. We aimed to assess the safety and activity of an anti-PD-1 antibody pembrolizumab in patients with locally advanced or metastatic urothelial cancer. Methods This study was part of the non-randomised, multi-cohort, open-label, phase 1b KEYNOTE-012 basket trial. We enrolled patients aged 18 years and older with a histologically or cytologically confirmed diagnosis of locally advanced or metastatic urothelial cancer, including cancers of the renal pelvis, ureter, bladder, or urethra, from eight hospitals in the USA and Israel. Patients were required to have at least 1% PD-L1 expression detected on the tumour cells or in tumour stroma, as determined by immunohistochemistry. Patients were given 10 mg/kg intravenous pembrolizumab every 2 weeks until disease progression, unacceptable toxic effects, or the end of the study (ie, 24 months of treatment). Primary endpoints were safety and overall response (defined by Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1), as assessed by a masked, independent central review. Safety was assessed in patients who received one or more doses of pembrolizumab (all-patients-as-treated population); activity was assessed in patients who received pembrolizumab, had measurable disease at baseline, and had one or more post-baseline scans, or discontinued because of progressive disease or treatment-related adverse events (full analysis set). This study is registered with ClinicalTrials.gov, number NCT01848834, and is no longer enrolling patients; follow-up is ongoing. Findings Between May 14, 2013, and Dec 10, 2013, 115 patients were tissue pre-screened as part of a two-part consent process. 61 (53%) patients were PD-L1 positive, of whom 33 were enrolled in this study. All enrolled patients received at least one dose of pembrolizumab and were included in the safety analyses. 27 patients comprised the full analysis set and were deemed assessable for activity. Six patients were not assessable: three discontinued study drug because of a non-treatment-related adverse event before the first post-baseline scan, two withdrew before the first post-baseline scan, and one had no measurable disease at baseline. The most common treatment-related adverse events were fatigue (six [18%] of 33 patients) and peripheral oedema (4 [12%]). Five (15%) patients had 11 grade 3 treatment-related adverse events; no single event occurred in more than one patient. Three (9%) patients experienced five serious treatment-related adverse events. After median follow-up of 13 months (range 1-26, IQR 5-23), an overall response was achieved in seven (26% [95% CI 11-46]) of 27 assessable patients, with three (11% [2-29]) complete and four (15% [4-34]) partial responses. Of the four deaths that occurred during the study (cardiac arrest, pneumonia, sepsis, and subarachnoid haemorrhage), none were deemed treatment related. Interpretation Pembrolizumab showed anti-tumour activity and acceptable safety in patients with advanced urothelial cancer, supporting ongoing phase 2 and 3 studies of pembrolizumab in this population. Funding Merck & Co., Inc. |
| Author | Juco, Jonathan Plimack, Elizabeth R Lunceford, Jared Bellmunt, Joaquim Perini, Rodolfo F Saraf, Sanatan O'Donnell, Peter H Berger, Raanan Chow, Laura Q M Gupta, Shilpa |
| Author_xml | – sequence: 1 givenname: Elizabeth R surname: Plimack fullname: Plimack, Elizabeth R email: elizabeth.plimack@fccc.edu organization: Fox Chase Cancer Center, Philadelphia, PA, USA – sequence: 2 givenname: Joaquim surname: Bellmunt fullname: Bellmunt, Joaquim organization: Dana-Farber Cancer Institute, Boston, MA, USA – sequence: 3 givenname: Shilpa surname: Gupta fullname: Gupta, Shilpa organization: University of Minnesota, Minneapolis, MN, USA – sequence: 4 givenname: Raanan surname: Berger fullname: Berger, Raanan organization: Chaim Sheba Medical Center at Tel Hashomer, Tel-Hashomer, Ramat-Gan, Israel – sequence: 5 givenname: Laura Q M surname: Chow fullname: Chow, Laura Q M organization: University of Washington, Seattle, WA, USA – sequence: 6 givenname: Jonathan surname: Juco fullname: Juco, Jonathan organization: Merck & Co., Inc. Kenilworth, NJ, USA – sequence: 7 givenname: Jared surname: Lunceford fullname: Lunceford, Jared organization: Merck & Co., Inc. Kenilworth, NJ, USA – sequence: 8 givenname: Sanatan surname: Saraf fullname: Saraf, Sanatan organization: Merck & Co., Inc. Kenilworth, NJ, USA – sequence: 9 givenname: Rodolfo F surname: Perini fullname: Perini, Rodolfo F organization: Merck & Co., Inc. Kenilworth, NJ, USA – sequence: 10 givenname: Peter H surname: O'Donnell fullname: O'Donnell, Peter H organization: University of Chicago, Chicago, IL, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28081914$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1200/JCO.2008.20.5534 10.1016/S0140-6736(16)00561-4 10.1038/ni.3415 10.1158/0008-5472.1089.65.3 10.1038/nrc3239 10.1158/1078-0432.CCR-08-0731 10.1007/s00262-006-0266-z 10.1016/S0140-6736(14)60958-2 10.1016/j.cell.2016.02.065 10.1200/JCO.2016.67.9761 10.1056/NEJMoa1406498 10.1200/JCO.2005.03.6699 10.1016/S1470-2045(10)70086-3 10.1016/S1470-2045(16)30066-3 10.1146/annurev.immunol.26.021607.090331 10.1016/S1470-2045(16)00175-3 10.1200/JCO.2015.64.8931 10.1182/blood-2009-04-216671 10.1002/cncr.22588 10.1126/science.aad0095 10.1038/nature14011 10.3322/caac.21332 10.1056/NEJMoa1501824 10.1056/NEJMoa1305133 10.1126/science.aaa1348 10.1016/j.ejca.2015.06.072 10.1038/nature13954 10.1038/nature13904 |
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| References | Rizvi, Hellmann, Snyder (bib26) 2015; 348 Pardoll (bib5) 2012; 12 Tumeh, Harview, Yearly (bib18) 2014; 515 Keir, Butte, Freeman, Sharpe (bib7) 2008; 26 Sonpavde, Sternberg, Rosenberg (bib23) 2010; 11 Muro, Chung, Shankaran (bib15) 2016; 17 Boorjian, Sheinin, Crispen (bib8) 2008; 14 Chang, Pearce (bib31) 2016; 17 Siegel, Miller, Jemal (bib1) 2016; 66 Herbst, Soria, Kowanetz (bib30) 2014; 515 Robert, Ribas, Wolchok (bib13) 2014; 384 Massard, Gordon, Sharma (bib24) 2016; 34 Inman, Sebo, Frigola (bib10) 2007; 109 Snyder, Makarov, Merghoub (bib25) 2014; 371 Ribas, Wolchuck, Robert (bib12) 2015; 51 Van Allen, Miao, Schilling (bib27) 2015; 350 Nanda, Chow, Dees (bib17) 2016; 34 Seiwert, Burtness, Mehra (bib16) 2016; 17 Hugo, Zaretsky, Sun (bib28) 2016; 165 Wilcox, Feldman, Wada (bib29) 2009; 114 (bib11) 2016 Powles, Eder, Fine (bib4) 2014; 515 Rosenberg, Hoffman-Censits, Powles (bib2) 2016; 387 (bib3) 2016 Sweeney, Roth, Kabbinavar (bib21) 2006; 24 Garon, Rizvi, Hui (bib14) 2015; 372 (bib19) 2015 Hirano, Kaneko, Tamura (bib6) 2005; 65 Hamid, Robert, Daud (bib22) 2013; 369 Nakanishi, Wada, Matsumoto (bib9) 2007; 56 Bellmunt, Théodore, Demkov (bib20) 2009; 27 Massard (10.1016/S1470-2045(17)30007-4_bib24) 2016; 34 Wilcox (10.1016/S1470-2045(17)30007-4_bib29) 2009; 114 Garon (10.1016/S1470-2045(17)30007-4_bib14) 2015; 372 Sonpavde (10.1016/S1470-2045(17)30007-4_bib23) 2010; 11 Snyder (10.1016/S1470-2045(17)30007-4_bib25) 2014; 371 Chang (10.1016/S1470-2045(17)30007-4_bib31) 2016; 17 Siegel (10.1016/S1470-2045(17)30007-4_bib1) 2016; 66 Hugo (10.1016/S1470-2045(17)30007-4_bib28) 2016; 165 Tumeh (10.1016/S1470-2045(17)30007-4_bib18) 2014; 515 (10.1016/S1470-2045(17)30007-4_bib11) 2016 Hamid (10.1016/S1470-2045(17)30007-4_bib22) 2013; 369 Rizvi (10.1016/S1470-2045(17)30007-4_bib26) 2015; 348 Seiwert (10.1016/S1470-2045(17)30007-4_bib16) 2016; 17 (10.1016/S1470-2045(17)30007-4_bib3) 2016 Hirano (10.1016/S1470-2045(17)30007-4_bib6) 2005; 65 Pardoll (10.1016/S1470-2045(17)30007-4_bib5) 2012; 12 Muro (10.1016/S1470-2045(17)30007-4_bib15) 2016; 17 Boorjian (10.1016/S1470-2045(17)30007-4_bib8) 2008; 14 Bellmunt (10.1016/S1470-2045(17)30007-4_bib20) 2009; 27 Keir (10.1016/S1470-2045(17)30007-4_bib7) 2008; 26 Robert (10.1016/S1470-2045(17)30007-4_bib13) 2014; 384 Nakanishi (10.1016/S1470-2045(17)30007-4_bib9) 2007; 56 Nanda (10.1016/S1470-2045(17)30007-4_bib17) 2016; 34 Van Allen (10.1016/S1470-2045(17)30007-4_bib27) 2015; 350 Rosenberg (10.1016/S1470-2045(17)30007-4_bib2) 2016; 387 Herbst (10.1016/S1470-2045(17)30007-4_bib30) 2014; 515 Inman (10.1016/S1470-2045(17)30007-4_bib10) 2007; 109 Ribas (10.1016/S1470-2045(17)30007-4_bib12) 2015; 51 Sweeney (10.1016/S1470-2045(17)30007-4_bib21) 2006; 24 Powles (10.1016/S1470-2045(17)30007-4_bib4) 2014; 515 28117845 - Nat Rev Urol. 2017 Mar;14(3):133 28081913 - Lancet Oncol. 2017 Feb;18(2):160-161 |
| References_xml | – volume: 17 start-page: 956 year: 2016 end-page: 965 ident: bib16 article-title: Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial publication-title: Lancet Oncol – volume: 372 start-page: 2018 year: 2015 end-page: 2028 ident: bib14 article-title: Pembrolizumab for the treatment of non-small-cell lung cancer publication-title: N Engl J Med – volume: 369 start-page: 134 year: 2013 end-page: 144 ident: bib22 article-title: Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma publication-title: N Engl J Med – volume: 348 start-page: 124 year: 2015 end-page: 128 ident: bib26 article-title: Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer publication-title: Science – volume: 515 start-page: 563 year: 2014 end-page: 567 ident: bib30 article-title: Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients publication-title: Nature – year: 2016 ident: bib11 publication-title: Keytruda prescribing information. October, 2016 update – volume: 26 start-page: 677 year: 2008 end-page: 704 ident: bib7 article-title: PD-1 and its ligands in tolerance and immunity publication-title: Annu Rev Immunol – volume: 17 start-page: 717 year: 2016 end-page: 726 ident: bib15 article-title: Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial publication-title: Lancet – year: 2016 ident: bib3 publication-title: Tecentriq (atezolizumab) injection, for intravenous use. 2016 – volume: 109 start-page: 1499 year: 2007 end-page: 1505 ident: bib10 article-title: PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression publication-title: Cancer – volume: 384 start-page: 1109 year: 2014 end-page: 1117 ident: bib13 article-title: Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial publication-title: Lancet – year: 2015 ident: bib19 article-title: Dako, an agilent technologies company, announces FDA approval of new companion diagnostic for lung cancer – volume: 34 start-page: 3119 year: 2016 end-page: 3125 ident: bib24 article-title: Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer publication-title: J Clin Oncol – volume: 371 start-page: 2189 year: 2014 end-page: 2199 ident: bib25 article-title: Genetic basis for clinical response to CTLA-4 blockade in melanoma publication-title: N Engl J Med – volume: 56 start-page: 1173 year: 2007 end-page: 1182 ident: bib9 article-title: Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers publication-title: Cancer Immunol Immunother – volume: 14 start-page: 4800 year: 2008 end-page: 4808 ident: bib8 article-title: T-cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival publication-title: Clin Cancer Res – volume: 24 start-page: 3451 year: 2006 end-page: 3457 ident: bib21 article-title: Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium publication-title: J Clin Oncol – volume: 515 start-page: 558 year: 2014 end-page: 562 ident: bib4 article-title: MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer publication-title: Nature – volume: 12 start-page: 252 year: 2012 end-page: 264 ident: bib5 article-title: The blockade of immune checkpoints in cancer immunotherapy publication-title: Nat Rev Cancer – volume: 387 start-page: 1909 year: 2016 end-page: 1920 ident: bib2 article-title: Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial publication-title: Lancet – volume: 515 start-page: 568 year: 2014 end-page: 571 ident: bib18 article-title: PD-1 blockade induces responses by inhibiting adaptive immune resistance publication-title: Nature – volume: 165 start-page: 35 year: 2016 end-page: 44 ident: bib28 article-title: Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma publication-title: Cell – volume: 51 start-page: e24 year: 2015 ident: bib12 article-title: Updated clinical efficacy of the anti-PD-1 monoclonal antibody pembrolizumab in 411 paitients with melanoma publication-title: Eur J Cancer – volume: 65 start-page: 1089 year: 2005 end-page: 1096 ident: bib6 article-title: Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity publication-title: Cancer Res – volume: 350 start-page: 207 year: 2015 end-page: 211 ident: bib27 article-title: Genomic correlates of response to CTLA-4 blockade in metastatic melanoma publication-title: Science – volume: 27 start-page: 4454 year: 2009 end-page: 4461 ident: bib20 article-title: Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract publication-title: J Clin Oncol – volume: 114 start-page: 2149 year: 2009 end-page: 2158 ident: bib29 article-title: B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders publication-title: Blood – volume: 66 start-page: 7 year: 2016 end-page: 30 ident: bib1 article-title: Cancer statistics, 2016 publication-title: CA Cancer J Clin – volume: 11 start-page: 861 year: 2010 end-page: 870 ident: bib23 article-title: Second-line systemic therapy and emerging drugs for metastatic transitional-cell carcinoma of the urothelium publication-title: Lancet Oncol – volume: 34 start-page: 2460 year: 2016 end-page: 2467 ident: bib17 article-title: Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study publication-title: J Clin Oncol – volume: 17 start-page: 364 year: 2016 end-page: 368 ident: bib31 article-title: Emerging concepts of T cell metabolism as a target of immunotherapy publication-title: Nat Immunol – volume: 27 start-page: 4454 year: 2009 ident: 10.1016/S1470-2045(17)30007-4_bib20 article-title: Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract publication-title: J Clin Oncol doi: 10.1200/JCO.2008.20.5534 – volume: 387 start-page: 1909 year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib2 article-title: Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial publication-title: Lancet doi: 10.1016/S0140-6736(16)00561-4 – volume: 17 start-page: 364 year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib31 article-title: Emerging concepts of T cell metabolism as a target of immunotherapy publication-title: Nat Immunol doi: 10.1038/ni.3415 – volume: 65 start-page: 1089 year: 2005 ident: 10.1016/S1470-2045(17)30007-4_bib6 article-title: Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity publication-title: Cancer Res doi: 10.1158/0008-5472.1089.65.3 – volume: 12 start-page: 252 year: 2012 ident: 10.1016/S1470-2045(17)30007-4_bib5 article-title: The blockade of immune checkpoints in cancer immunotherapy publication-title: Nat Rev Cancer doi: 10.1038/nrc3239 – volume: 14 start-page: 4800 year: 2008 ident: 10.1016/S1470-2045(17)30007-4_bib8 article-title: T-cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-08-0731 – volume: 56 start-page: 1173 year: 2007 ident: 10.1016/S1470-2045(17)30007-4_bib9 article-title: Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers publication-title: Cancer Immunol Immunother doi: 10.1007/s00262-006-0266-z – volume: 384 start-page: 1109 year: 2014 ident: 10.1016/S1470-2045(17)30007-4_bib13 article-title: Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial publication-title: Lancet doi: 10.1016/S0140-6736(14)60958-2 – volume: 165 start-page: 35 year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib28 article-title: Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma publication-title: Cell doi: 10.1016/j.cell.2016.02.065 – volume: 34 start-page: 3119 year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib24 article-title: Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2016.67.9761 – volume: 371 start-page: 2189 year: 2014 ident: 10.1016/S1470-2045(17)30007-4_bib25 article-title: Genetic basis for clinical response to CTLA-4 blockade in melanoma publication-title: N Engl J Med doi: 10.1056/NEJMoa1406498 – volume: 24 start-page: 3451 year: 2006 ident: 10.1016/S1470-2045(17)30007-4_bib21 article-title: Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium publication-title: J Clin Oncol doi: 10.1200/JCO.2005.03.6699 – volume: 11 start-page: 861 year: 2010 ident: 10.1016/S1470-2045(17)30007-4_bib23 article-title: Second-line systemic therapy and emerging drugs for metastatic transitional-cell carcinoma of the urothelium publication-title: Lancet Oncol doi: 10.1016/S1470-2045(10)70086-3 – volume: 17 start-page: 956 year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib16 article-title: Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial publication-title: Lancet Oncol doi: 10.1016/S1470-2045(16)30066-3 – volume: 26 start-page: 677 year: 2008 ident: 10.1016/S1470-2045(17)30007-4_bib7 article-title: PD-1 and its ligands in tolerance and immunity publication-title: Annu Rev Immunol doi: 10.1146/annurev.immunol.26.021607.090331 – volume: 17 start-page: 717 year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib15 article-title: Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial publication-title: Lancet doi: 10.1016/S1470-2045(16)00175-3 – volume: 34 start-page: 2460 year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib17 article-title: Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study publication-title: J Clin Oncol doi: 10.1200/JCO.2015.64.8931 – volume: 114 start-page: 2149 year: 2009 ident: 10.1016/S1470-2045(17)30007-4_bib29 article-title: B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders publication-title: Blood doi: 10.1182/blood-2009-04-216671 – volume: 109 start-page: 1499 year: 2007 ident: 10.1016/S1470-2045(17)30007-4_bib10 article-title: PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression publication-title: Cancer doi: 10.1002/cncr.22588 – volume: 350 start-page: 207 year: 2015 ident: 10.1016/S1470-2045(17)30007-4_bib27 article-title: Genomic correlates of response to CTLA-4 blockade in metastatic melanoma publication-title: Science doi: 10.1126/science.aad0095 – volume: 515 start-page: 563 year: 2014 ident: 10.1016/S1470-2045(17)30007-4_bib30 article-title: Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients publication-title: Nature doi: 10.1038/nature14011 – volume: 66 start-page: 7 year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib1 article-title: Cancer statistics, 2016 publication-title: CA Cancer J Clin doi: 10.3322/caac.21332 – volume: 372 start-page: 2018 year: 2015 ident: 10.1016/S1470-2045(17)30007-4_bib14 article-title: Pembrolizumab for the treatment of non-small-cell lung cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa1501824 – volume: 369 start-page: 134 year: 2013 ident: 10.1016/S1470-2045(17)30007-4_bib22 article-title: Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma publication-title: N Engl J Med doi: 10.1056/NEJMoa1305133 – volume: 348 start-page: 124 year: 2015 ident: 10.1016/S1470-2045(17)30007-4_bib26 article-title: Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer publication-title: Science doi: 10.1126/science.aaa1348 – volume: 51 start-page: e24 year: 2015 ident: 10.1016/S1470-2045(17)30007-4_bib12 article-title: Updated clinical efficacy of the anti-PD-1 monoclonal antibody pembrolizumab in 411 paitients with melanoma publication-title: Eur J Cancer doi: 10.1016/j.ejca.2015.06.072 – volume: 515 start-page: 568 year: 2014 ident: 10.1016/S1470-2045(17)30007-4_bib18 article-title: PD-1 blockade induces responses by inhibiting adaptive immune resistance publication-title: Nature doi: 10.1038/nature13954 – volume: 515 start-page: 558 year: 2014 ident: 10.1016/S1470-2045(17)30007-4_bib4 article-title: MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer publication-title: Nature doi: 10.1038/nature13904 – year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib3 – year: 2016 ident: 10.1016/S1470-2045(17)30007-4_bib11 – reference: 28117845 - Nat Rev Urol. 2017 Mar;14(3):133 – reference: 28081913 - Lancet Oncol. 2017 Feb;18(2):160-161 |
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| Snippet | PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit. We aimed to assess... Summary Background PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit.... Background PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit. We aimed... |
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| SubjectTerms | Adult Aged Aged, 80 and over Antibodies, Monoclonal, Humanized - therapeutic use Antineoplastic Agents - therapeutic use Breast cancer Cancer therapies Chemotherapy Female Follow-Up Studies Gastric cancer Head & neck cancer Hematology, Oncology and Palliative Medicine Hepatitis Humans Ligands Male Metastasis Middle Aged Neoplasm Metastasis Neoplasm Recurrence, Local - drug therapy Neoplasm Recurrence, Local - pathology Neoplasm Staging Oncology Pharmaceutical industry Prognosis Response rates Safety Studies Survival Rate Tumors Urologic Neoplasms - drug therapy Urologic Neoplasms - pathology |
| Title | Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study |
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