{"id":91107,"date":"2023-10-30T17:17:47","date_gmt":"2023-10-30T17:17:47","guid":{"rendered":"https:\/\/touchoncology.com\/?post_type=media_gallery&p=91107"},"modified":"2023-11-01T09:43:13","modified_gmt":"2023-11-01T09:43:13","slug":"__trashed","status":"publish","type":"media_gallery","link":"https:\/\/touchoncology.com\/breast-cancer\/conference-hub\/__trashed\/","title":{"rendered":"Trastuzumab duocarmazine in HER2+ metastatic breast cancer – TULIP trial results: Philippe Aftimos, ESMO 2023"},"content":{"rendered":"

The final results of the phase 3, TULIP trial (<\/span>NCT03262935<\/span><\/a>), which compared trastuzumab duocarmazine (T-Duo) with physician’s choice of therapy in previously treated HER2-positive metastatic breast cancer, were presented at ESMO 2023.\u00a0<\/span><\/p>\n

Dr. Philippe Aftimos<\/strong>, the study investigator from the Institute Jules Bordet in Belgium, presented the results at the conference and then discussed them with us at touchONCOLOGY.<\/span><\/p>\n

Questions<\/b><\/p>\n

    \n
  1. What are the current unmet needs in the treatment of HER2-positive metastatic breast cancer (MBC)? (0.20)<\/span><\/li>\n
  2. What is trastuzumab duocarmazine (T-Duo) and what is its mechanism of action? (1:33)<\/span><\/li>\n
  3. What were the aims, design, and eligibility criteria of the TULIP study? (1:58)<\/span><\/li>\n
  4. What were the study findings in terms of the primary and secondary endpoints? (2:53)<\/span><\/li>\n
  5. What were the study findings in terms of safety? (3:48)<\/span><\/li>\n
  6. Are there any questions that remain unanswered and what will be the next steps in the clinical development of T-Duo? (4:36)<\/span><\/li>\n<\/ol>\n

    Disclosures:<\/strong> Philippe Aftimos has acted as a consultant for Amcure, Amgen, Boehringer Ingelheim, Daiichi Sankyo, Deloitte, Eli Lilly,Gilead, Incyte, Macrogenics, Menarini,Novartis, Synthon and Radius, and recieved grant\/research support from Roche.<\/span><\/p>\n

    Support:<\/strong> Interview and filming supported by Touch Medical Media Ltd. Interview conducted by Gina Furnival<\/span><\/p>\n

    Filmed in coverage of the ESMO 2023<\/i><\/b><\/p>\n

    Click here for more content on<\/span><\/i> breast cancer<\/span><\/i><\/a> & for further <\/i>ESMO 2023 highlights<\/a> visit here<\/span><\/i>.<\/i><\/b><\/p>\n

    Transcript<\/strong><\/p>\n

    I am Phillip Aftimos. I’m a medical oncologist working in breast oncology and precision medicine and I’m also the Head of the Clinical Trials unit in a comprehensive cancer center in Brussels called Institute Jules Bordet, affiliated with the Universt\u00e9 Libre de Brussels.<\/p>\n

    Q1. What are the current unmet needs in the treatment of HER2-positive metastatic breast cancer (MBC)? (0.20)<\/strong><\/p>\n

    HER2-positive\u00a0 metastatic\u00a0 breast\u00a0 cancer\u00a0 has\u00a0 seen\u00a0 a\u00a0 lot\u00a0 of\u00a0 advances\u00a0 in\u00a0 the\u00a0 last\u00a0 few\u00a0 years.\u00a0 So\u00a0 just\u00a0 to\u00a0 set\u00a0 the\u00a0 scene,\u00a0 HER2-positive\u00a0 breast\u00a0 cancer\u00a0 is\u00a0 20\u00a0 percent\u00a0 of\u00a0 full\u00a0 breast\u00a0 cancers.\u00a0 This\u00a0 was\u00a0 a\u00a0 very\u00a0 tough\u00a0 cancer\u00a0 to\u00a0 treat\u00a0 because\u00a0 of\u00a0 aggressivity,\u00a0 but\u00a0 we\u00a0 started\u00a0 therapies\u00a0 that\u00a0 are\u00a0 aimed\u00a0 at\u00a0 the\u00a0 HER2\u00a0 overexpression\u00a0 and\u00a0 the\u00a0 HER2\u00a0 amplification,\u00a0 and\u00a0 we\u00a0 improved\u00a0 a\u00a0 lot,\u00a0 and\u00a0 actually,\u00a0 the\u00a0 overall\u00a0 survival\u00a0 of\u00a0 patients\u00a0 has\u00a0 improved\u00a0 a\u00a0 lot.\u00a0 There\u00a0 are\u00a0 still\u00a0 some\u00a0 unmet\u00a0 needs.\u00a0 There\u00a0 is\u00a0 now\u00a0 an\u00a0 antibody-drug\u00a0 conjugate\u00a0 called\u00a0 trastuzumab\u00a0 deruxtecan,\u00a0 which\u00a0 is\u00a0 highly\u00a0 potent\u00a0 and\u00a0 approved\u00a0 in\u00a0 the\u00a0 metastatic\u00a0 setting.\u00a0 However,\u00a0 however,\u00a0 we\u00a0 have\u00a0 very\u00a0 little\u00a0 data\u00a0 on\u00a0 treatment\u00a0 after\u00a0 trastuzumab\u00a0 deruxtecan\u00a0 when\u00a0 patients\u00a0 have\u00a0 disease\u00a0 progression.\u00a0 And\u00a0 another\u00a0 area\u00a0 of\u00a0 unmet\u00a0 need,\u00a0 are\u00a0 the\u00a0 central\u00a0 nervous\u00a0 system\u00a0 metastasis.\u00a0 We\u00a0 know\u00a0 that\u00a0 this\u00a0 type\u00a0 of\u00a0 disease\u00a0 has\u00a0 a\u00a0 propensity\u00a0 to\u00a0 go\u00a0 into\u00a0 the\u00a0 brain\u00a0 and\u00a0 the\u00a0 meninges,\u00a0 and,\u00a0 the\u00a0 last\u00a0 few\u00a0 years\u00a0 I\u00a0 have\u00a0 seen\u00a0 some\u00a0 drugs\u00a0 whose\u00a0 activity\u00a0 there,\u00a0 such\u00a0 as\u00a0 tucatinib,\u00a0 but\u00a0 this\u00a0 is\u00a0 still\u00a0 I\u00a0 believe\u00a0 an\u00a0 area\u00a0 of\u00a0 need.<\/p>\n

    Q2. What is trastuzumab duocarmazine (T-Duo) and what is its mechanism of action? (1:33)<\/strong><\/p>\n

    It’s\u00a0 actually\u00a0 a\u00a0 third\u00a0 generation,\u00a0 antibody\u00a0 drug-conjugate\u00a0 targeting\u00a0 the\u00a0 HER2\u00a0 receptor.\u00a0 It\u00a0 has\u00a0 a\u00a0 cleavable\u00a0 linker\u00a0 and\u00a0 the\u00a0 payload\u00a0 is\u00a0 duocarmycin,\u00a0 which\u00a0 is\u00a0 a\u00a0 minor\u00a0 group\u00a0 binder\u00a0 activating\u00a0 agent\u00a0 with\u00a0 a\u00a0 drug-antibody\u00a0 ratio\u00a0 between\u00a0 2.4\u00a0 and\u00a0 2.8.<\/p>\n

    Q3. What were the aims, design, and eligibility criteria of the TULIP study? (1:58)<\/strong><\/p>\n

    This\u00a0 is\u00a0 a\u00a0 phase\u00a0 3\u00a0 study,\u00a0 that\u00a0 randomized\u00a0 patients\u00a0 2:1\u00a0 to\u00a0 T-Duo\u00a0 versus\u00a0 treatment\u00a0 of\u00a0 physician’s\u00a0 choice,\u00a0 which\u00a0 was\u00a0 chemotherapy\u00a0 in\u00a0 combination\u00a0 with\u00a0 an\u00a0 anti-HER2\u00a0 therapy.\u00a0 So\u00a0 this\u00a0 could\u00a0 have\u00a0 been\u00a0 eribulin\u00a0 plus\u00a0 trastuzumab,\u00a0 capecitabine\u00a0 plus\u00a0 trastuzumab,\u00a0 lapatinib\u00a0 plus\u00a0 capecitabine,\u00a0 vinorelbine\u00a0 plus\u00a0 trastuzumab.<\/p>\n

    So\u00a0 patients,<\/span>\u00a0 should\u00a0 have\u00a0 had\u00a0 advanced\u00a0 breast\u00a0 cancer\u00a0 that\u00a0 was\u00a0 HER2-positive.\u00a0 This\u00a0 could\u00a0 have\u00a0 been\u00a0 metastatic\u00a0 breast\u00a0 cancer\u00a0 or\u00a0 locally\u00a0 advanced,\u00a0 not\u00a0 amenable\u00a0 to\u00a0 surgical\u00a0 resection.\u00a0 Four\u00a0 hundred\u00a0 and\u00a0 thirty\u00a0 seven\u00a0 patients\u00a0 were\u00a0 randomized,\u00a0 and,\u00a0 they\u00a0 should\u00a0 have\u00a0 received\u00a0 two\u00a0 prior\u00a0 lines\u00a0 of\u00a0 therapy\u00a0 for\u00a0 metastatic\u00a0 disease,\u00a0 or\u00a0 should\u00a0 have\u00a0 received,\u00a0 TDM1.<\/p>\n

    Patients\u00a0 with<\/span>\u00a0 stable\u00a0 brain\u00a0 metastases\u00a0 were\u00a0 allowed\u00a0 in\u00a0 the\u00a0 study.<\/p>\n

    Q4. What were the study findings in terms of the primary and secondary endpoints? (2:53)<\/strong><\/p>\n

    The\u00a0 primary\u00a0 endpoint\u00a0 was\u00a0 presented\u00a0 at\u00a0 ESMO\u00a0 2021,\u00a0 so\u00a0 this\u00a0 was\u00a0 centrally\u00a0 assessed\u00a0 progression\u00a0 free\u00a0 survival\u00a0 and\u00a0 there\u00a0 the\u00a0 study\u00a0 met\u00a0 its\u00a0 objective,\u00a0 with\u00a0 a\u00a0 PFS\u00a0 of\u00a0 7\u00a0 months\u00a0 for\u00a0 the\u00a0 investigational\u00a0 arm\u00a0 of\u00a0 T-Duo\u00a0 versus\u00a0 4.9\u00a0 months\u00a0 in\u00a0 the\u00a0 treatment\u00a0 of\u00a0 physician’s\u00a0 choice\u00a0 and\u00a0 the\u00a0 hazard\u00a0 ratio\u00a0 was\u00a0 0.36.<\/p>\n

    Together\u00a0 endpoints<\/span>\u00a0 included\u00a0 investigator\u00a0 assessed\u00a0 PFS,\u00a0 overall\u00a0 survival\u00a0 response\u00a0 rate,\u00a0 adverse\u00a0 events\u00a0 and\u00a0 the\u00a0 quality\u00a0 of\u00a0 life.\u00a0 For\u00a0 the\u00a0 secondary\u00a0 endpoint,\u00a0 there\u00a0 was\u00a0 no\u00a0 improvement,\u00a0 statistically\u00a0 significant\u00a0 improvement\u00a0 in\u00a0 overall\u00a0 survival.\u00a0 Numerically\u00a0 there\u00a0 was\u00a0 an\u00a0 improvement\u00a0 with\u00a0 T-Duo\u00a0 from\u00a0 21\u00a0 months\u00a0 versus\u00a0 19.5\u00a0 months,\u00a0 but\u00a0 again,\u00a0 as\u00a0 I\u00a0 said,\u00a0 this\u00a0 was\u00a0 not\u00a0 statistically\u00a0 significant.<\/p>\n

    Q5. What were the study findings in terms of safety? (3:48)<\/strong><\/p>\n

    T-Duo,\u00a0 like\u00a0 other\u00a0 antibody-drug\u00a0 conjugates,\u00a0 actually,\u00a0 has,\u00a0 mainly\u00a0 ophthalmological\u00a0 adverse\u00a0 events.\u00a0 So\u00a0 either\u00a0 keratitis\u00a0 or\u00a0 conjunctivitis.\u00a0 So\u00a0 those\u00a0 were\u00a0 the\u00a0 most\u00a0 prevalent\u00a0 adverse\u00a0 events\u00a0 in\u00a0 the\u00a0 investigational\u00a0 arm.\u00a0 So\u00a0 it\u00a0 was\u00a0 as\u00a0 high\u00a0 as\u00a0 78\u00a0 percent,\u00a0 including\u00a0 28\u00a0 percent\u00a0 that\u00a0 were\u00a0 Grade\u00a0 3,\u00a0 and\u00a0 about\u00a0 21\u00a0 percent\u00a0 of\u00a0 patients\u00a0 had\u00a0 treatment\u00a0 discontinuation,\u00a0 and\u00a0 about\u00a0 23\u00a0 percent\u00a0 had\u00a0 dose\u00a0 modifications.<\/p>\n

    Like,\u00a0 also,<\/span>\u00a0 like\u00a0 other\u00a0 antibody-drug\u00a0 conjugates,\u00a0 there\u00a0 was\u00a0 some\u00a0 interstitial\u00a0 lung\u00a0 disease\u00a0 (ILD).\u00a0 So\u00a0 the\u00a0 rate,\u00a0 the\u00a0 prevalence\u00a0 was\u00a0 7.6\u00a0 percent.<\/p>\n

    Grade\u00a0 3<\/span>\u00a0 was\u00a0 2.4\u00a0 percent,\u00a0 and,\u00a0 about\u00a0 5\u00a0 percent\u00a0 of\u00a0 patients\u00a0 discontinued\u00a0 because\u00a0 of\u00a0 ILD.<\/p>\n

    Q6. Are there any questions that remain unanswered and what will be the next steps in the clinical development of T-Duo? (4:36)<\/strong><\/p>\n

    Well\u00a0 I\u00a0 believe\u00a0 the\u00a0 study,\u00a0 was\u00a0 performed,\u00a0 whilst\u00a0 trastuzumab\u00a0 deruxtecan\u00a0 was\u00a0 not\u00a0 yet\u00a0 the\u00a0 standard\u00a0 of\u00a0 care.<\/p>\n

    So\u00a0 we\u00a0 still,\u00a0 we\u00a0 still\u00a0 have\u00a0 the\u00a0 question\u00a0 of\u00a0 what\u00a0 to\u00a0 do\u00a0 post-trastuzumab\u00a0 deruxtecan\u00a0 currently.\u00a0 Approved\u00a0 as\u00a0 early\u00a0 as\u00a0 the\u00a0 second-line\u00a0 or\u00a0 even\u00a0 first-line\u00a0 in\u00a0 patients\u00a0 that\u00a0 relapse\u00a0 quickly\u00a0 after\u00a0 trastuzumab\u00a0 and\u00a0 pertuzumab.<\/p>\n

    For\u00a0 me,<\/span>\u00a0 the\u00a0 logical\u00a0 step\u00a0 would\u00a0 be\u00a0 to\u00a0 evaluate\u00a0 efficacy\u00a0 post\u00a0 T-DXd\u00a0 but\u00a0 also,\u00a0 do\u00a0 a\u00a0 larger\u00a0 study\u00a0 in\u00a0 the\u00a0 HER2-low\u00a0 subset\u00a0 because\u00a0 this\u00a0 is\u00a0 also\u00a0 now\u00a0 an\u00a0 area\u00a0 of\u00a0 investigational\u00a0 anti-HER2\u00a0 therapies,\u00a0 but\u00a0 you\u00a0 also\u00a0 have\u00a0 an\u00a0 approved\u00a0 drug\u00a0 that\u00a0 is,\u00a0 again\u00a0 trastuzumab\u00a0 deruxtecan.<\/p>\n

    Subtitles and transcript are autogenerated.<\/em><\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"

    The final results of the phase 3, TULIP trial (NCT03262935), which compared trastuzumab duocarmazine (T-Duo) with physician’s choice of therapy in previously treated HER2-positive metastatic breast cancer, were presented at ESMO 2023.\u00a0 Dr. Philippe Aftimos, the study investigator from the Institute Jules Bordet in Belgium, presented the results at the conference and then discussed them […]<\/p>\n","protected":false},"featured_media":91122,"template":"","class_list":["post-91107","media_gallery","type-media_gallery","status-publish","has-post-thumbnail","hentry","vocabulary_1-breast-cancer","video_categories-esmo-highlights"],"acf":[],"_links":{"self":[{"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/media_gallery\/91107","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/media_gallery"}],"about":[{"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/types\/media_gallery"}],"version-history":[{"count":13,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/media_gallery\/91107\/revisions"}],"predecessor-version":[{"id":123407,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/media_gallery\/91107\/revisions\/123407"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/media\/91122"}],"wp:attachment":[{"href":"https:\/\/touchoncology.com\/wp-json\/wp\/v2\/media?parent=91107"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}