Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial
Summary Background Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously...
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| Veröffentlicht in: | The Lancet (British edition) 2017-08, Vol.390 (10094), p.555-566 |
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| creator | Prince, H Miles, Prof Kim, Youn H, Prof Horwitz, Steven M, MD Dummer, Reinhard, Prof Scarisbrick, Julia, MD Quaglino, Pietro, Prof Zinzani, Pier Luigi, Prof Wolter, Pascal, MD Sanches, Jose A, PhD Ortiz-Romero, Pablo L, Prof Akilov, Oleg E, MD Geskin, Larisa, MD Trotman, Judith, MD Taylor, Kerry, MBBS Dalle, Stephane, Prof Weichenthal, Michael, Prof Walewski, Jan, Prof Fisher, David, MD Dréno, Brigitte, Prof Stadler, Rudolf, Prof Feldman, Tatyana, MD Kuzel, Timothy M, Prof Wang, Yinghui, MS Palanca-Wessels, Maria Corinna, MD Zagadailov, Erin, PharmD Trepicchio, William L, PhD Zhang, Wenwen, PhD Lin, Hui-Min, PhD Liu, Yi, PhD Huebner, Dirk, MD Little, Meredith, MPH Whittaker, Sean, Prof Duvic, Madeleine, Prof |
| description | Summary Background Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. Methods In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5–50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov , number NCT01578499. Findings Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4–26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1–58·4; p |
| doi_str_mv | 10.1016/S0140-6736(17)31266-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1908428722</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0140673617312667</els_id><sourcerecordid>1925901912</sourcerecordid><originalsourceid>FETCH-LOGICAL-c500t-3d67b00ba8387406e42e950a81611a4b27ee4b9ca0bdef09290f15c0a9aa0b43</originalsourceid><addsrcrecordid>eNqFkc-O0zAQxiMEYrsLjwCyxIGu1MA4ceKEA6tS_koVHOgBcbEcZ6p6SexgOxV9Hx4Up10WaS-cbNm_-Wa--ZLkCYUXFGj58itQBmnJ83JO-WVOs7JM-b1kRhlnacH4t_vJ7BY5S869vwYAVkLxMDnLqhKA5tks-f3GoQnjL93LhuyxtUEbYh0ZdgevlZbmuSdqZ7VCEj9Wb3NIB-t10HskagzSoB092aQKu450h37Y2V6S-XK9Wn7-vrx8RaSJhQGdkUFbI7sFsQOatJMNxruTprW99tguYkvpkeQL0o9diA1NcEiC07J7lDzYys7j45vzItm8f7dZfUzXXz58Wi3XqSoAQpq3JW8AGlnlFWdQIsuwLkBWtKRUsibjiKyplYSmxS3UWQ1bWiiQtYxPLL9I5ifZwdmfI_og4mSTsZNLQWuoWFbxLIvoszvotR2jx26isqIGWtOJKk6UctZ7h1sxuLhodxAUxJSiOKYopogE5eKYouCx7umN-tj02N5W_Y0tAlcnAOM29hqd8EqjUdhqhyqI1ur_tnh9R0F12mglux94QP_PjfCZgJPIpEH5UYHnfwD7n8Dp</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1925901912</pqid></control><display><type>article</type><title>Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial</title><source>Elsevier ScienceDirect Journals Complete</source><creator>Prince, H Miles, Prof ; Kim, Youn H, Prof ; Horwitz, Steven M, MD ; Dummer, Reinhard, Prof ; Scarisbrick, Julia, MD ; Quaglino, Pietro, Prof ; Zinzani, Pier Luigi, Prof ; Wolter, Pascal, MD ; Sanches, Jose A, PhD ; Ortiz-Romero, Pablo L, Prof ; Akilov, Oleg E, MD ; Geskin, Larisa, MD ; Trotman, Judith, MD ; Taylor, Kerry, MBBS ; Dalle, Stephane, Prof ; Weichenthal, Michael, Prof ; Walewski, Jan, Prof ; Fisher, David, MD ; Dréno, Brigitte, Prof ; Stadler, Rudolf, Prof ; Feldman, Tatyana, MD ; Kuzel, Timothy M, Prof ; Wang, Yinghui, MS ; Palanca-Wessels, Maria Corinna, MD ; Zagadailov, Erin, PharmD ; Trepicchio, William L, PhD ; Zhang, Wenwen, PhD ; Lin, Hui-Min, PhD ; Liu, Yi, PhD ; Huebner, Dirk, MD ; Little, Meredith, MPH ; Whittaker, Sean, Prof ; Duvic, Madeleine, Prof</creator><creatorcontrib>Prince, H Miles, Prof ; Kim, Youn H, Prof ; Horwitz, Steven M, MD ; Dummer, Reinhard, Prof ; Scarisbrick, Julia, MD ; Quaglino, Pietro, Prof ; Zinzani, Pier Luigi, Prof ; Wolter, Pascal, MD ; Sanches, Jose A, PhD ; Ortiz-Romero, Pablo L, Prof ; Akilov, Oleg E, MD ; Geskin, Larisa, MD ; Trotman, Judith, MD ; Taylor, Kerry, MBBS ; Dalle, Stephane, Prof ; Weichenthal, Michael, Prof ; Walewski, Jan, Prof ; Fisher, David, MD ; Dréno, Brigitte, Prof ; Stadler, Rudolf, Prof ; Feldman, Tatyana, MD ; Kuzel, Timothy M, Prof ; Wang, Yinghui, MS ; Palanca-Wessels, Maria Corinna, MD ; Zagadailov, Erin, PharmD ; Trepicchio, William L, PhD ; Zhang, Wenwen, PhD ; Lin, Hui-Min, PhD ; Liu, Yi, PhD ; Huebner, Dirk, MD ; Little, Meredith, MPH ; Whittaker, Sean, Prof ; Duvic, Madeleine, Prof ; ALCANZA study group</creatorcontrib><description>Summary Background Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. Methods In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5–50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov , number NCT01578499. Findings Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4–26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1–58·4; p<0·0001). Grade 3–4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. Interpretation Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Funding Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(17)31266-7</identifier><identifier>PMID: 28600132</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anaplastic large-cell lymphoma ; Cancer therapies ; CD30 antigen ; Chemotherapy ; Clinical trials ; Evidence-based medicine ; Fungal infections ; Genetics ; Immunotherapy ; Internal Medicine ; Lymphocytes ; Lymphocytes T ; Lymphoma ; Methotrexate ; Monoclonal antibodies ; Mycosis ; Mycosis fungoides ; Patients ; Peripheral neuropathy ; Pharmaceutical industry ; Pharmaceuticals ; Quality of life ; Skin ; T-cell lymphoma ; Targeted cancer therapy</subject><ispartof>The Lancet (British edition), 2017-08, Vol.390 (10094), p.555-566</ispartof><rights>Elsevier Ltd</rights><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Aug 5, 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-3d67b00ba8387406e42e950a81611a4b27ee4b9ca0bdef09290f15c0a9aa0b43</citedby><cites>FETCH-LOGICAL-c500t-3d67b00ba8387406e42e950a81611a4b27ee4b9ca0bdef09290f15c0a9aa0b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0140673617312667$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28600132$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Prince, H Miles, Prof</creatorcontrib><creatorcontrib>Kim, Youn H, Prof</creatorcontrib><creatorcontrib>Horwitz, Steven M, MD</creatorcontrib><creatorcontrib>Dummer, Reinhard, Prof</creatorcontrib><creatorcontrib>Scarisbrick, Julia, MD</creatorcontrib><creatorcontrib>Quaglino, Pietro, Prof</creatorcontrib><creatorcontrib>Zinzani, Pier Luigi, Prof</creatorcontrib><creatorcontrib>Wolter, Pascal, MD</creatorcontrib><creatorcontrib>Sanches, Jose A, PhD</creatorcontrib><creatorcontrib>Ortiz-Romero, Pablo L, Prof</creatorcontrib><creatorcontrib>Akilov, Oleg E, MD</creatorcontrib><creatorcontrib>Geskin, Larisa, MD</creatorcontrib><creatorcontrib>Trotman, Judith, MD</creatorcontrib><creatorcontrib>Taylor, Kerry, MBBS</creatorcontrib><creatorcontrib>Dalle, Stephane, Prof</creatorcontrib><creatorcontrib>Weichenthal, Michael, Prof</creatorcontrib><creatorcontrib>Walewski, Jan, Prof</creatorcontrib><creatorcontrib>Fisher, David, MD</creatorcontrib><creatorcontrib>Dréno, Brigitte, Prof</creatorcontrib><creatorcontrib>Stadler, Rudolf, Prof</creatorcontrib><creatorcontrib>Feldman, Tatyana, MD</creatorcontrib><creatorcontrib>Kuzel, Timothy M, Prof</creatorcontrib><creatorcontrib>Wang, Yinghui, MS</creatorcontrib><creatorcontrib>Palanca-Wessels, Maria Corinna, MD</creatorcontrib><creatorcontrib>Zagadailov, Erin, PharmD</creatorcontrib><creatorcontrib>Trepicchio, William L, PhD</creatorcontrib><creatorcontrib>Zhang, Wenwen, PhD</creatorcontrib><creatorcontrib>Lin, Hui-Min, PhD</creatorcontrib><creatorcontrib>Liu, Yi, PhD</creatorcontrib><creatorcontrib>Huebner, Dirk, MD</creatorcontrib><creatorcontrib>Little, Meredith, MPH</creatorcontrib><creatorcontrib>Whittaker, Sean, Prof</creatorcontrib><creatorcontrib>Duvic, Madeleine, Prof</creatorcontrib><creatorcontrib>ALCANZA study group</creatorcontrib><title>Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Summary Background Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. Methods In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5–50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov , number NCT01578499. Findings Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4–26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1–58·4; p<0·0001). Grade 3–4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. Interpretation Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Funding Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.</description><subject>Anaplastic large-cell lymphoma</subject><subject>Cancer therapies</subject><subject>CD30 antigen</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Evidence-based medicine</subject><subject>Fungal infections</subject><subject>Genetics</subject><subject>Immunotherapy</subject><subject>Internal Medicine</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Methotrexate</subject><subject>Monoclonal antibodies</subject><subject>Mycosis</subject><subject>Mycosis fungoides</subject><subject>Patients</subject><subject>Peripheral neuropathy</subject><subject>Pharmaceutical industry</subject><subject>Pharmaceuticals</subject><subject>Quality of life</subject><subject>Skin</subject><subject>T-cell lymphoma</subject><subject>Targeted cancer 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vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial</title><author>Prince, H Miles, Prof ; Kim, Youn H, Prof ; Horwitz, Steven M, MD ; Dummer, Reinhard, Prof ; Scarisbrick, Julia, MD ; Quaglino, Pietro, Prof ; Zinzani, Pier Luigi, Prof ; Wolter, Pascal, MD ; Sanches, Jose A, PhD ; Ortiz-Romero, Pablo L, Prof ; Akilov, Oleg E, MD ; Geskin, Larisa, MD ; Trotman, Judith, MD ; Taylor, Kerry, MBBS ; Dalle, Stephane, Prof ; Weichenthal, Michael, Prof ; Walewski, Jan, Prof ; Fisher, David, MD ; Dréno, Brigitte, Prof ; Stadler, Rudolf, Prof ; Feldman, Tatyana, MD ; Kuzel, Timothy M, Prof ; Wang, Yinghui, MS ; Palanca-Wessels, Maria Corinna, MD ; Zagadailov, Erin, PharmD ; Trepicchio, William L, PhD ; Zhang, Wenwen, PhD ; Lin, Hui-Min, PhD ; Liu, Yi, PhD ; Huebner, Dirk, MD ; Little, Meredith, MPH ; Whittaker, Sean, Prof ; Duvic, Madeleine, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-3d67b00ba8387406e42e950a81611a4b27ee4b9ca0bdef09290f15c0a9aa0b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Anaplastic large-cell lymphoma</topic><topic>Cancer therapies</topic><topic>CD30 antigen</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Evidence-based medicine</topic><topic>Fungal infections</topic><topic>Genetics</topic><topic>Immunotherapy</topic><topic>Internal Medicine</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Methotrexate</topic><topic>Monoclonal antibodies</topic><topic>Mycosis</topic><topic>Mycosis fungoides</topic><topic>Patients</topic><topic>Peripheral neuropathy</topic><topic>Pharmaceutical industry</topic><topic>Pharmaceuticals</topic><topic>Quality of life</topic><topic>Skin</topic><topic>T-cell lymphoma</topic><topic>Targeted cancer therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Prince, H Miles, Prof</creatorcontrib><creatorcontrib>Kim, Youn H, Prof</creatorcontrib><creatorcontrib>Horwitz, Steven M, MD</creatorcontrib><creatorcontrib>Dummer, Reinhard, Prof</creatorcontrib><creatorcontrib>Scarisbrick, Julia, MD</creatorcontrib><creatorcontrib>Quaglino, Pietro, Prof</creatorcontrib><creatorcontrib>Zinzani, Pier Luigi, Prof</creatorcontrib><creatorcontrib>Wolter, Pascal, MD</creatorcontrib><creatorcontrib>Sanches, Jose A, PhD</creatorcontrib><creatorcontrib>Ortiz-Romero, Pablo L, Prof</creatorcontrib><creatorcontrib>Akilov, Oleg E, MD</creatorcontrib><creatorcontrib>Geskin, Larisa, MD</creatorcontrib><creatorcontrib>Trotman, Judith, MD</creatorcontrib><creatorcontrib>Taylor, Kerry, MBBS</creatorcontrib><creatorcontrib>Dalle, Stephane, Prof</creatorcontrib><creatorcontrib>Weichenthal, Michael, Prof</creatorcontrib><creatorcontrib>Walewski, Jan, Prof</creatorcontrib><creatorcontrib>Fisher, David, MD</creatorcontrib><creatorcontrib>Dréno, Brigitte, Prof</creatorcontrib><creatorcontrib>Stadler, Rudolf, Prof</creatorcontrib><creatorcontrib>Feldman, Tatyana, MD</creatorcontrib><creatorcontrib>Kuzel, Timothy M, Prof</creatorcontrib><creatorcontrib>Wang, Yinghui, MS</creatorcontrib><creatorcontrib>Palanca-Wessels, Maria Corinna, MD</creatorcontrib><creatorcontrib>Zagadailov, Erin, PharmD</creatorcontrib><creatorcontrib>Trepicchio, William L, PhD</creatorcontrib><creatorcontrib>Zhang, Wenwen, PhD</creatorcontrib><creatorcontrib>Lin, Hui-Min, PhD</creatorcontrib><creatorcontrib>Liu, Yi, PhD</creatorcontrib><creatorcontrib>Huebner, Dirk, MD</creatorcontrib><creatorcontrib>Little, Meredith, MPH</creatorcontrib><creatorcontrib>Whittaker, Sean, Prof</creatorcontrib><creatorcontrib>Duvic, Madeleine, Prof</creatorcontrib><creatorcontrib>ALCANZA study 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Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Prince, H Miles, Prof</au><au>Kim, Youn H, Prof</au><au>Horwitz, Steven M, MD</au><au>Dummer, Reinhard, Prof</au><au>Scarisbrick, Julia, MD</au><au>Quaglino, Pietro, Prof</au><au>Zinzani, Pier Luigi, Prof</au><au>Wolter, Pascal, MD</au><au>Sanches, Jose A, PhD</au><au>Ortiz-Romero, Pablo L, Prof</au><au>Akilov, Oleg E, MD</au><au>Geskin, Larisa, MD</au><au>Trotman, Judith, MD</au><au>Taylor, Kerry, MBBS</au><au>Dalle, Stephane, Prof</au><au>Weichenthal, Michael, Prof</au><au>Walewski, Jan, Prof</au><au>Fisher, David, MD</au><au>Dréno, Brigitte, Prof</au><au>Stadler, Rudolf, Prof</au><au>Feldman, Tatyana, MD</au><au>Kuzel, Timothy M, Prof</au><au>Wang, Yinghui, MS</au><au>Palanca-Wessels, Maria Corinna, MD</au><au>Zagadailov, Erin, PharmD</au><au>Trepicchio, William L, PhD</au><au>Zhang, Wenwen, PhD</au><au>Lin, Hui-Min, PhD</au><au>Liu, Yi, PhD</au><au>Huebner, Dirk, MD</au><au>Little, Meredith, MPH</au><au>Whittaker, Sean, Prof</au><au>Duvic, Madeleine, Prof</au><aucorp>ALCANZA study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2017-08-05</date><risdate>2017</risdate><volume>390</volume><issue>10094</issue><spage>555</spage><epage>566</epage><pages>555-566</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><abstract>Summary Background Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. Methods In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5–50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov , number NCT01578499. Findings Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4–26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1–58·4; p<0·0001). Grade 3–4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. Interpretation Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Funding Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28600132</pmid><doi>10.1016/S0140-6736(17)31266-7</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2017-08, Vol.390 (10094), p.555-566 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1908428722 |
| source | Elsevier ScienceDirect Journals Complete |
| subjects | Anaplastic large-cell lymphoma Cancer therapies CD30 antigen Chemotherapy Clinical trials Evidence-based medicine Fungal infections Genetics Immunotherapy Internal Medicine Lymphocytes Lymphocytes T Lymphoma Methotrexate Monoclonal antibodies Mycosis Mycosis fungoides Patients Peripheral neuropathy Pharmaceutical industry Pharmaceuticals Quality of life Skin T-cell lymphoma Targeted cancer therapy |
| title | Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial |
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