Kathleen N. Moore , Domenica Lorusso , Ana Oaknin , Amit Oza , Nicoletta Colombo , Toon Van Gorp , David M. O'Malley , Susana Banerjee , Conleth G. Murphy , Philipp Harter , Gottfried E. Konecny , Patricia Pautier , Michael Method , Yuemei Wang , Robert L. Coleman , Michael Birrer , Ursula A. Matulonis
{"title":"米韦曲单抗索拉坦星单药治疗叶酸受体α表达复发性卵巢癌的安全性和耐受性:综合安全性总结。","authors":"Kathleen N. Moore , Domenica Lorusso , Ana Oaknin , Amit Oza , Nicoletta Colombo , Toon Van Gorp , David M. O'Malley , Susana Banerjee , Conleth G. Murphy , Philipp Harter , Gottfried E. Konecny , Patricia Pautier , Michael Method , Yuemei Wang , Robert L. Coleman , Michael Birrer , Ursula A. Matulonis","doi":"10.1016/j.ygyno.2024.10.013","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Mirvetuximab soravtansine-gynx (MIRV) is a novel antibody-drug conjugate targeting folate receptor alpha (FRα), which is overexpressed in epithelial ovarian cancer (EOC), with limited expression on normal tissues. This integrated safety summary sought to characterize the safety profile of MIRV monotherapy in participants with FRα-expressing recurrent EOC.</div></div><div><h3>Methods</h3><div>Safety data were retrospectively analyzed from 4 clinical studies (phase 1 trial [<span><span>NCT01609556</span><svg><path></path></svg></span>], phase 3 FORWARD I [<span><span>NCT02631876</span><svg><path></path></svg></span>], phase 2 SORAYA [<span><span>NCT04296890</span><svg><path></path></svg></span>], phase 3 MIRASOL [<span><span>NCT04209855</span><svg><path></path></svg></span>]) that evaluated participants with FRα-expressing recurrent EOC who received ≥1 dose of MIRV 6 mg/kg adjusted ideal body weight every 3 weeks.</div></div><div><h3>Results</h3><div>In this analysis of 682 participants, 94 % had platinum-resistant ovarian cancer (PROC). Blurred vision (43 %), nausea (41 %), diarrhea (39 %), and fatigue (35 %) were the most common treatment-emergent adverse events (TEAEs) and were primarily grade 1–2 in severity. Grade ≥ 3 TEAEs occurred in 48 % of participants, with the most common being keratopathy and blurred vision (5 % each). Most TEAEs were managed with supportive care and dose modifications, and only 12 % of participants experienced a TEAE leading to discontinuation (1 % due to ocular events). No corneal ulcerations or perforations have been reported. Median time to onset of blurred vision and keratopathy was 5.9 and 6.7 weeks, respectively. Most blurred vision events and keratopathy events resolved completely (71 % and 66 %, respectively) or partially (15 % and 14 %, respectively).</div></div><div><h3>Conclusions</h3><div>As demonstrated among 682 participants, the safety profile of MIRV is well tolerated and consists primarily of low-grade gastrointestinal, fatigue, headache, peripheral neuropathy, and resolvable ocular adverse events.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety and tolerability of mirvetuximab soravtansine monotherapy for folate receptor alpha–expressing recurrent ovarian cancer: An integrated safety summary\",\"authors\":\"Kathleen N. Moore , Domenica Lorusso , Ana Oaknin , Amit Oza , Nicoletta Colombo , Toon Van Gorp , David M. O'Malley , Susana Banerjee , Conleth G. Murphy , Philipp Harter , Gottfried E. Konecny , Patricia Pautier , Michael Method , Yuemei Wang , Robert L. Coleman , Michael Birrer , Ursula A. Matulonis\",\"doi\":\"10.1016/j.ygyno.2024.10.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Mirvetuximab soravtansine-gynx (MIRV) is a novel antibody-drug conjugate targeting folate receptor alpha (FRα), which is overexpressed in epithelial ovarian cancer (EOC), with limited expression on normal tissues. This integrated safety summary sought to characterize the safety profile of MIRV monotherapy in participants with FRα-expressing recurrent EOC.</div></div><div><h3>Methods</h3><div>Safety data were retrospectively analyzed from 4 clinical studies (phase 1 trial [<span><span>NCT01609556</span><svg><path></path></svg></span>], phase 3 FORWARD I [<span><span>NCT02631876</span><svg><path></path></svg></span>], phase 2 SORAYA [<span><span>NCT04296890</span><svg><path></path></svg></span>], phase 3 MIRASOL [<span><span>NCT04209855</span><svg><path></path></svg></span>]) that evaluated participants with FRα-expressing recurrent EOC who received ≥1 dose of MIRV 6 mg/kg adjusted ideal body weight every 3 weeks.</div></div><div><h3>Results</h3><div>In this analysis of 682 participants, 94 % had platinum-resistant ovarian cancer (PROC). Blurred vision (43 %), nausea (41 %), diarrhea (39 %), and fatigue (35 %) were the most common treatment-emergent adverse events (TEAEs) and were primarily grade 1–2 in severity. Grade ≥ 3 TEAEs occurred in 48 % of participants, with the most common being keratopathy and blurred vision (5 % each). Most TEAEs were managed with supportive care and dose modifications, and only 12 % of participants experienced a TEAE leading to discontinuation (1 % due to ocular events). No corneal ulcerations or perforations have been reported. Median time to onset of blurred vision and keratopathy was 5.9 and 6.7 weeks, respectively. Most blurred vision events and keratopathy events resolved completely (71 % and 66 %, respectively) or partially (15 % and 14 %, respectively).</div></div><div><h3>Conclusions</h3><div>As demonstrated among 682 participants, the safety profile of MIRV is well tolerated and consists primarily of low-grade gastrointestinal, fatigue, headache, peripheral neuropathy, and resolvable ocular adverse events.</div></div>\",\"PeriodicalId\":12853,\"journal\":{\"name\":\"Gynecologic oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-10-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gynecologic oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0090825824011636\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gynecologic oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0090825824011636","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Safety and tolerability of mirvetuximab soravtansine monotherapy for folate receptor alpha–expressing recurrent ovarian cancer: An integrated safety summary
Objective
Mirvetuximab soravtansine-gynx (MIRV) is a novel antibody-drug conjugate targeting folate receptor alpha (FRα), which is overexpressed in epithelial ovarian cancer (EOC), with limited expression on normal tissues. This integrated safety summary sought to characterize the safety profile of MIRV monotherapy in participants with FRα-expressing recurrent EOC.
Methods
Safety data were retrospectively analyzed from 4 clinical studies (phase 1 trial [NCT01609556], phase 3 FORWARD I [NCT02631876], phase 2 SORAYA [NCT04296890], phase 3 MIRASOL [NCT04209855]) that evaluated participants with FRα-expressing recurrent EOC who received ≥1 dose of MIRV 6 mg/kg adjusted ideal body weight every 3 weeks.
Results
In this analysis of 682 participants, 94 % had platinum-resistant ovarian cancer (PROC). Blurred vision (43 %), nausea (41 %), diarrhea (39 %), and fatigue (35 %) were the most common treatment-emergent adverse events (TEAEs) and were primarily grade 1–2 in severity. Grade ≥ 3 TEAEs occurred in 48 % of participants, with the most common being keratopathy and blurred vision (5 % each). Most TEAEs were managed with supportive care and dose modifications, and only 12 % of participants experienced a TEAE leading to discontinuation (1 % due to ocular events). No corneal ulcerations or perforations have been reported. Median time to onset of blurred vision and keratopathy was 5.9 and 6.7 weeks, respectively. Most blurred vision events and keratopathy events resolved completely (71 % and 66 %, respectively) or partially (15 % and 14 %, respectively).
Conclusions
As demonstrated among 682 participants, the safety profile of MIRV is well tolerated and consists primarily of low-grade gastrointestinal, fatigue, headache, peripheral neuropathy, and resolvable ocular adverse events.
期刊介绍:
Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published.
Research Areas Include:
• Cell and molecular biology
• Chemotherapy
• Cytology
• Endocrinology
• Epidemiology
• Genetics
• Gynecologic surgery
• Immunology
• Pathology
• Radiotherapy