104 230

Cited 1071 times in

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer

DC Field Value Language
dc.contributor.author손주혁-
dc.date.accessioned2022-09-06T06:41:49Z-
dc.date.available2022-09-06T06:41:49Z-
dc.date.issued2020-02-
dc.identifier.issn0028-4793-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/190269-
dc.description.abstractIn this single-group, phase 2 study, the use of trastuzumab deruxtecan resulted in a response in 60% of women with HER2-positive advanced breast cancer who had received a median of six previous lines of therapy. The drug was associated with myelosuppression and gastrointestinal toxicity; interstitial lung disease was reported in 13.6% of the patients. Background Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. In a phase 1 dose-finding study, a majority of the patients with advanced HER2-positive breast cancer had a response to trastuzumab deruxtecan (median response duration, 20.7 months). The efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine requires confirmation. Methods In this two-part, open-label, single-group, multicenter, phase 2 study, we evaluated trastuzumab deruxtecan in adults with pathologically documented HER2-positive metastatic breast cancer who had received previous treatment with trastuzumab emtansine. In the first part of the study, we evaluated three different doses of trastuzumab deruxtecan to establish a recommended dose; in the second part, we evaluated the efficacy and safety of the recommended dose. The primary end point was the objective response, according to independent central review. Key secondary end points were the disease-control rate, clinical-benefit rate, duration of response and progression-free survival, and safety. Results Overall, 184 patients who had undergone a median of six previous treatments received the recommended dose of trastuzumab deruxtecan (5.4 mg per kilogram of body weight). In the intention-to-treat analysis, a response to therapy was reported in 112 patients (60.9%; 95% confidence interval [CI], 53.4 to 68.0). The median duration of follow-up was 11.1 months (range, 0.7 to 19.9). The median response duration was 14.8 months (95% CI, 13.8 to 16.9), and the median duration of progression-free survival was 16.4 months (95% CI, 12.7 to not reached). During the study, the most common adverse events of grade 3 or higher were a decreased neutrophil count (in 20.7% of the patients), anemia (in 8.7%), and nausea (in 7.6%). On independent adjudication, the trial drug was associated with interstitial lung disease in 13.6% of the patients (grade 1 or 2, 10.9%; grade 3 or 4, 0.5%; and grade 5, 2.2%). Conclusions Trastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer. In addition to nausea and myelosuppression, interstitial lung disease was observed in a subgroup of patients and requires attention to pulmonary symptoms and careful monitoring. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast01 ClinicalTrials.gov number, .)-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherMassachusetts Medical Society-
dc.relation.isPartOfNEW ENGLAND JOURNAL OF MEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAdult-
dc.subject.MESHAged-
dc.subject.MESHAged, 80 and over-
dc.subject.MESHAntibodies, Monoclonal, Humanized / administration & dosage*-
dc.subject.MESHAntibodies, Monoclonal, Humanized / adverse effects-
dc.subject.MESHAntineoplastic Combined Chemotherapy Protocols / adverse effects-
dc.subject.MESHAntineoplastic Combined Chemotherapy Protocols / therapeutic use*-
dc.subject.MESHBreast Neoplasms / drug therapy*-
dc.subject.MESHBreast Neoplasms / mortality-
dc.subject.MESHBreast Neoplasms / pathology-
dc.subject.MESHCamptothecin / administration & dosage-
dc.subject.MESHCamptothecin / adverse effects-
dc.subject.MESHCamptothecin / analogs & derivatives*-
dc.subject.MESHConsolidation Chemotherapy-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHImmunoconjugates / administration & dosage*-
dc.subject.MESHImmunoconjugates / adverse effects-
dc.subject.MESHIntention to Treat Analysis-
dc.subject.MESHKaplan-Meier Estimate-
dc.subject.MESHLung Diseases, Interstitial / chemically induced*-
dc.subject.MESHMiddle Aged-
dc.subject.MESHProgression-Free Survival-
dc.subject.MESHReceptor, ErbB-2 / analysis-
dc.subject.MESHReceptor, ErbB-2 / antagonists & inhibitors*-
dc.subject.MESHTrastuzumab-
dc.titleTrastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorShanu Modi-
dc.contributor.googleauthorCristina Saura-
dc.contributor.googleauthorToshinari Yamashita-
dc.contributor.googleauthorYeon Hee Park-
dc.contributor.googleauthorSung-Bae Kim-
dc.contributor.googleauthorKenji Tamura-
dc.contributor.googleauthorFabrice Andre-
dc.contributor.googleauthorHiroji Iwata-
dc.contributor.googleauthorYoshinori Ito-
dc.contributor.googleauthorJunji Tsurutani-
dc.contributor.googleauthorJoohyuk Sohn-
dc.contributor.googleauthorNeelima Denduluri-
dc.contributor.googleauthorChristophe Perrin-
dc.contributor.googleauthorKenjiro Aogi-
dc.contributor.googleauthorEriko Tokunaga-
dc.contributor.googleauthorSeock-Ah Im-
dc.contributor.googleauthorKeun Seok Lee-
dc.contributor.googleauthorSara A Hurvitz-
dc.contributor.googleauthorJavier Cortes-
dc.contributor.googleauthorCaleb Lee-
dc.contributor.googleauthorShuquan Chen-
dc.contributor.googleauthorLin Zhang-
dc.contributor.googleauthorJavad Shahidi-
dc.contributor.googleauthorAntoine Yver-
dc.contributor.googleauthorIan Krop-
dc.identifier.doi10.1056/NEJMoa1914510-
dc.contributor.localIdA01995-
dc.relation.journalcodeJ02371-
dc.identifier.eissn1533-4406-
dc.identifier.pmid31825192-
dc.contributor.alternativeNameSohn, Joo Hyuk-
dc.contributor.affiliatedAuthor손주혁-
dc.citation.volume382-
dc.citation.number7-
dc.citation.startPage610-
dc.citation.endPage621-
dc.identifier.bibliographicCitationNEW ENGLAND JOURNAL OF MEDICINE, Vol.382(7) : 610-621, 2020-02-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.