Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer
Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival ben...
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| Veröffentlicht in: | Journal of clinical oncology 2023-09, Vol.41 (25), p.4107-4117 |
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| creator | O'Donnell, Peter H Milowsky, Matthew I Petrylak, Daniel P Hoimes, Christopher J Flaig, Thomas W Mar, Nataliya Moon, Helen H Friedlander, Terence W McKay, Rana R Bilen, Mehmet A Srinivas, Sandy Burgess, Earle F Ramamurthy, Chethan George, Saby Geynisman, Daniel M Bracarda, Sergio Borchiellini, Delphine Geoffrois, Lionnel Maroto Rey, Jose Pablo Ferrario, Christiano Carret, Anne-Sophie Yu, Yao Guseva, Maria Homet Moreno, Blanca Rosenberg, Jonathan E |
| description | Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.
In Cohort K of the EV-103 phase Ib/II study, cisplatin-ineligible patients with previously untreated la/mUC were randomly assigned 1:1 to receive EV as monotherapy or in combination with Pembro. The primary end point was confirmed objective response rate (cORR) per blinded independent central review. Secondary end points included duration of response (DOR) and safety. There were no formal statistical comparisons between treatment arms.
The cORR was 64.5% (95% CI, 52.7 to 75.1) and 45.2% (95% CI, 33.5 to 57.3) for patients treated with EV + Pembro (N = 76) and EV monotherapy (N = 73), respectively. The median DOR was not reached for the combination and was 13.2 months for monotherapy; 65.4% and 56.3% of patients who responded to the combination and monotherapy, respectively, maintained a response at 12 months. The most common grade 3 or higher treatment-related adverse events (TRAEs) in patients treated with the combination were maculopapular rash (17.1%), fatigue (9.2%), and neutropenia (9.2%). EV TRAEs of special interest (any grade) in the combination arm included skin reactions (67.1%) and peripheral neuropathy (60.5%).
EV + Pembro showed a high cORR with durable responses as 1L treatment in cisplatin-ineligible patients with la/mUC. Patients who received EV monotherapy had a response and safety profile consistent with previous studies. Adverse events for EV + Pembro were manageable, with no new safety signals observed. |
| doi_str_mv | 10.1200/JCO.22.02887 |
| format | Article |
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In Cohort K of the EV-103 phase Ib/II study, cisplatin-ineligible patients with previously untreated la/mUC were randomly assigned 1:1 to receive EV as monotherapy or in combination with Pembro. The primary end point was confirmed objective response rate (cORR) per blinded independent central review. Secondary end points included duration of response (DOR) and safety. There were no formal statistical comparisons between treatment arms.
The cORR was 64.5% (95% CI, 52.7 to 75.1) and 45.2% (95% CI, 33.5 to 57.3) for patients treated with EV + Pembro (N = 76) and EV monotherapy (N = 73), respectively. The median DOR was not reached for the combination and was 13.2 months for monotherapy; 65.4% and 56.3% of patients who responded to the combination and monotherapy, respectively, maintained a response at 12 months. The most common grade 3 or higher treatment-related adverse events (TRAEs) in patients treated with the combination were maculopapular rash (17.1%), fatigue (9.2%), and neutropenia (9.2%). EV TRAEs of special interest (any grade) in the combination arm included skin reactions (67.1%) and peripheral neuropathy (60.5%).
EV + Pembro showed a high cORR with durable responses as 1L treatment in cisplatin-ineligible patients with la/mUC. Patients who received EV monotherapy had a response and safety profile consistent with previous studies. Adverse events for EV + Pembro were manageable, with no new safety signals observed.</description><identifier>ISSN: 0732-183X</identifier><identifier>ISSN: 1527-7755</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/JCO.22.02887</identifier><identifier>PMID: 37369081</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health</publisher><subject>Antibodies, Monoclonal, Humanized - therapeutic use ; Carcinoma, Transitional Cell ; Cisplatin - adverse effects ; Humans ; ORIGINAL REPORTS</subject><ispartof>Journal of clinical oncology, 2023-09, Vol.41 (25), p.4107-4117</ispartof><rights>2023 by American Society of Clinical Oncology 2023 American Society of Clinical Oncology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-4d4ac45d7c4bcb0b4f0dc637d58e3c579120dcabc16395a2f1a65530eaa57083</citedby><cites>FETCH-LOGICAL-c385t-4d4ac45d7c4bcb0b4f0dc637d58e3c579120dcabc16395a2f1a65530eaa57083</cites><orcidid>0000-0003-4003-1103 ; 0000-0002-1423-5295 ; 0000-0003-4293-4680 ; 0000-0002-0444-5870 ; 0000-0001-6145-9040 ; 0000-0001-6165-5797 ; 0000-0002-0703-2959 ; 0000-0003-2637-4249 ; 0000-0002-0581-7963 ; 0000-0003-2650-0049 ; 0000-0003-2485-6201 ; 0000-0001-6723-6948 ; 0000-0003-3935-9638 ; 0000-0002-8965-8129 ; 0000-0002-3630-4941 ; 0000-0001-8980-2410</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3716,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37369081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>O'Donnell, Peter H</creatorcontrib><creatorcontrib>Milowsky, Matthew I</creatorcontrib><creatorcontrib>Petrylak, Daniel P</creatorcontrib><creatorcontrib>Hoimes, Christopher J</creatorcontrib><creatorcontrib>Flaig, Thomas W</creatorcontrib><creatorcontrib>Mar, Nataliya</creatorcontrib><creatorcontrib>Moon, Helen H</creatorcontrib><creatorcontrib>Friedlander, Terence W</creatorcontrib><creatorcontrib>McKay, Rana R</creatorcontrib><creatorcontrib>Bilen, Mehmet A</creatorcontrib><creatorcontrib>Srinivas, Sandy</creatorcontrib><creatorcontrib>Burgess, Earle F</creatorcontrib><creatorcontrib>Ramamurthy, Chethan</creatorcontrib><creatorcontrib>George, Saby</creatorcontrib><creatorcontrib>Geynisman, Daniel M</creatorcontrib><creatorcontrib>Bracarda, Sergio</creatorcontrib><creatorcontrib>Borchiellini, Delphine</creatorcontrib><creatorcontrib>Geoffrois, Lionnel</creatorcontrib><creatorcontrib>Maroto Rey, Jose Pablo</creatorcontrib><creatorcontrib>Ferrario, Christiano</creatorcontrib><creatorcontrib>Carret, Anne-Sophie</creatorcontrib><creatorcontrib>Yu, Yao</creatorcontrib><creatorcontrib>Guseva, Maria</creatorcontrib><creatorcontrib>Homet Moreno, Blanca</creatorcontrib><creatorcontrib>Rosenberg, Jonathan E</creatorcontrib><title>Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><description>Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.
In Cohort K of the EV-103 phase Ib/II study, cisplatin-ineligible patients with previously untreated la/mUC were randomly assigned 1:1 to receive EV as monotherapy or in combination with Pembro. The primary end point was confirmed objective response rate (cORR) per blinded independent central review. Secondary end points included duration of response (DOR) and safety. There were no formal statistical comparisons between treatment arms.
The cORR was 64.5% (95% CI, 52.7 to 75.1) and 45.2% (95% CI, 33.5 to 57.3) for patients treated with EV + Pembro (N = 76) and EV monotherapy (N = 73), respectively. The median DOR was not reached for the combination and was 13.2 months for monotherapy; 65.4% and 56.3% of patients who responded to the combination and monotherapy, respectively, maintained a response at 12 months. The most common grade 3 or higher treatment-related adverse events (TRAEs) in patients treated with the combination were maculopapular rash (17.1%), fatigue (9.2%), and neutropenia (9.2%). EV TRAEs of special interest (any grade) in the combination arm included skin reactions (67.1%) and peripheral neuropathy (60.5%).
EV + Pembro showed a high cORR with durable responses as 1L treatment in cisplatin-ineligible patients with la/mUC. Patients who received EV monotherapy had a response and safety profile consistent with previous studies. Adverse events for EV + Pembro were manageable, with no new safety signals observed.</description><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Carcinoma, Transitional Cell</subject><subject>Cisplatin - adverse effects</subject><subject>Humans</subject><subject>ORIGINAL REPORTS</subject><issn>0732-183X</issn><issn>1527-7755</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU9v1DAQxS0EokvhxhnlyIEs_hPH3hOqogJFi7qHFrhZE9vpGjnx1nZWKp-FD4u7Wyo4jfTmN2_seQi9JnhJKMbvv3SXS0qXmEopnqAF4VTUQnD-FC2wYLQmkv04QS9S-okxaSTjz9EJE6xdYUkW6Pf5NISY5xH66ps1Ibup-u7ytgrxUMOcq40d-xi8-3WgCtC5tPNQ0Ppist7duN7balMEO-V0HN9Eu3dhTv6uup5ytJCtqdZBgy_KmdnDpItQlny1GVIus7q6jiFvix_4qrvvx5fo2QA-2VcP9RRdfTy_6j7X68tPF93ZutZM8lw3pgHdcCN00-se982AjW6ZMFxaprlYlTsZDb0mLVtxoAOBlnOGLQAXWLJT9OFou5v70RpdfhHBq110I8Q7FcCp_zuT26qbsFcES05ZK4rD2weHGG5nm7IaXdLWe5hsOYKikuFWUNbQgr47ojqGlKIdHvcQrO4DVSVQRak6BFrwN_--7RH-myD7A3cxoJ4</recordid><startdate>20230901</startdate><enddate>20230901</enddate><creator>O'Donnell, Peter H</creator><creator>Milowsky, Matthew I</creator><creator>Petrylak, Daniel P</creator><creator>Hoimes, Christopher J</creator><creator>Flaig, Thomas W</creator><creator>Mar, Nataliya</creator><creator>Moon, Helen H</creator><creator>Friedlander, Terence W</creator><creator>McKay, Rana R</creator><creator>Bilen, Mehmet A</creator><creator>Srinivas, Sandy</creator><creator>Burgess, Earle F</creator><creator>Ramamurthy, Chethan</creator><creator>George, Saby</creator><creator>Geynisman, Daniel M</creator><creator>Bracarda, Sergio</creator><creator>Borchiellini, Delphine</creator><creator>Geoffrois, Lionnel</creator><creator>Maroto Rey, Jose Pablo</creator><creator>Ferrario, Christiano</creator><creator>Carret, Anne-Sophie</creator><creator>Yu, Yao</creator><creator>Guseva, Maria</creator><creator>Homet Moreno, Blanca</creator><creator>Rosenberg, Jonathan E</creator><general>Wolters Kluwer Health</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4003-1103</orcidid><orcidid>https://orcid.org/0000-0002-1423-5295</orcidid><orcidid>https://orcid.org/0000-0003-4293-4680</orcidid><orcidid>https://orcid.org/0000-0002-0444-5870</orcidid><orcidid>https://orcid.org/0000-0001-6145-9040</orcidid><orcidid>https://orcid.org/0000-0001-6165-5797</orcidid><orcidid>https://orcid.org/0000-0002-0703-2959</orcidid><orcidid>https://orcid.org/0000-0003-2637-4249</orcidid><orcidid>https://orcid.org/0000-0002-0581-7963</orcidid><orcidid>https://orcid.org/0000-0003-2650-0049</orcidid><orcidid>https://orcid.org/0000-0003-2485-6201</orcidid><orcidid>https://orcid.org/0000-0001-6723-6948</orcidid><orcidid>https://orcid.org/0000-0003-3935-9638</orcidid><orcidid>https://orcid.org/0000-0002-8965-8129</orcidid><orcidid>https://orcid.org/0000-0002-3630-4941</orcidid><orcidid>https://orcid.org/0000-0001-8980-2410</orcidid></search><sort><creationdate>20230901</creationdate><title>Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer</title><author>O'Donnell, Peter H ; 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Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.
In Cohort K of the EV-103 phase Ib/II study, cisplatin-ineligible patients with previously untreated la/mUC were randomly assigned 1:1 to receive EV as monotherapy or in combination with Pembro. The primary end point was confirmed objective response rate (cORR) per blinded independent central review. Secondary end points included duration of response (DOR) and safety. There were no formal statistical comparisons between treatment arms.
The cORR was 64.5% (95% CI, 52.7 to 75.1) and 45.2% (95% CI, 33.5 to 57.3) for patients treated with EV + Pembro (N = 76) and EV monotherapy (N = 73), respectively. The median DOR was not reached for the combination and was 13.2 months for monotherapy; 65.4% and 56.3% of patients who responded to the combination and monotherapy, respectively, maintained a response at 12 months. The most common grade 3 or higher treatment-related adverse events (TRAEs) in patients treated with the combination were maculopapular rash (17.1%), fatigue (9.2%), and neutropenia (9.2%). EV TRAEs of special interest (any grade) in the combination arm included skin reactions (67.1%) and peripheral neuropathy (60.5%).
EV + Pembro showed a high cORR with durable responses as 1L treatment in cisplatin-ineligible patients with la/mUC. Patients who received EV monotherapy had a response and safety profile consistent with previous studies. Adverse events for EV + Pembro were manageable, with no new safety signals observed.</abstract><cop>United States</cop><pub>Wolters Kluwer Health</pub><pmid>37369081</pmid><doi>10.1200/JCO.22.02887</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-4003-1103</orcidid><orcidid>https://orcid.org/0000-0002-1423-5295</orcidid><orcidid>https://orcid.org/0000-0003-4293-4680</orcidid><orcidid>https://orcid.org/0000-0002-0444-5870</orcidid><orcidid>https://orcid.org/0000-0001-6145-9040</orcidid><orcidid>https://orcid.org/0000-0001-6165-5797</orcidid><orcidid>https://orcid.org/0000-0002-0703-2959</orcidid><orcidid>https://orcid.org/0000-0003-2637-4249</orcidid><orcidid>https://orcid.org/0000-0002-0581-7963</orcidid><orcidid>https://orcid.org/0000-0003-2650-0049</orcidid><orcidid>https://orcid.org/0000-0003-2485-6201</orcidid><orcidid>https://orcid.org/0000-0001-6723-6948</orcidid><orcidid>https://orcid.org/0000-0003-3935-9638</orcidid><orcidid>https://orcid.org/0000-0002-8965-8129</orcidid><orcidid>https://orcid.org/0000-0002-3630-4941</orcidid><orcidid>https://orcid.org/0000-0001-8980-2410</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0732-183X |
| ispartof | Journal of clinical oncology, 2023-09, Vol.41 (25), p.4107-4117 |
| issn | 0732-183X 1527-7755 1527-7755 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10852367 |
| source | MEDLINE; American Society of Clinical Oncology Online Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Antibodies, Monoclonal, Humanized - therapeutic use Carcinoma, Transitional Cell Cisplatin - adverse effects Humans ORIGINAL REPORTS |
| title | Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T11%3A17%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Enfortumab%20Vedotin%20With%20or%20Without%20Pembrolizumab%20in%20Cisplatin-Ineligible%20Patients%20With%20Previously%20Untreated%20Locally%20Advanced%20or%20Metastatic%20Urothelial%20Cancer&rft.jtitle=Journal%20of%20clinical%20oncology&rft.au=O'Donnell,%20Peter%20H&rft.date=2023-09-01&rft.volume=41&rft.issue=25&rft.spage=4107&rft.epage=4117&rft.pages=4107-4117&rft.issn=0732-183X&rft.eissn=1527-7755&rft_id=info:doi/10.1200/JCO.22.02887&rft_dat=%3Cproquest_pubme%3E2830672342%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2830672342&rft_id=info:pmid/37369081&rfr_iscdi=true |