Antonio Giordano, Priya U Kumthekar, Qingchun Jin, Busem Binboga Kurt, Siyang Ren, Tianyu Li, Jose Pablo Leone, Elizabeth A Mittendorf, Alyssa M Pereslete, Laura Sharp, Raechel Davis, Molly DiLullo, Nabihah Tayob, Erica L Mayer, Eric P Winer, Sara M Tolaney, Nancy U Lin
{"title":"atezolizumab、pertuzumab和大剂量曲妥珠单抗治疗HER2阳性乳腺癌患者中枢神经系统转移的II期研究。","authors":"Antonio Giordano, Priya U Kumthekar, Qingchun Jin, Busem Binboga Kurt, Siyang Ren, Tianyu Li, Jose Pablo Leone, Elizabeth A Mittendorf, Alyssa M Pereslete, Laura Sharp, Raechel Davis, Molly DiLullo, Nabihah Tayob, Erica L Mayer, Eric P Winer, Sara M Tolaney, Nancy U Lin","doi":"10.1158/1078-0432.CCR-24-1161","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response.</p><p><strong>Patients and methods: </strong>This was a single-arm, multicenter, phase II trial of atezolizumab, pertuzumab, and high-dose trastuzumab for patients with HER2-positive breast cancer brain metastases. Participants received atezolizumab 1,200 mg i.v. every 3 weeks, pertuzumab (loading dosage 840 mg i.v., then 420 mg i.v. every 3 weeks), and high-dose trastuzumab (6 mg/kg i.v. weekly for 24 weeks, then 6 mg/kg i.v. every 3 weeks). The primary endpoint was CNS overall response rate per Response Assessment in Neuro-Oncology Brain Metastases criteria. Key secondary endpoints included CBR, overall survival, and safety and tolerability of the combination.</p><p><strong>Results: </strong>Among 19 enrolled participants, two had a confirmed intracranial partial response for a CNS overall response rate of 10.5% (90% confidence interval, 1.9%-29.6%). The study did not meet the prespecified efficacy threshold and was terminated early. The CBR was 42.1% at 18 weeks and 31.6% at 24 weeks. Seven patients (36.8%) required a dose delay or hold, and the most frequent any-grade adverse events were diarrhea (26.3%) and fatigue (26.3%).</p><p><strong>Conclusions: </strong>The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive breast cancer brain metastases.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":10.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528201/pdf/","citationCount":"0","resultStr":"{\"title\":\"A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer.\",\"authors\":\"Antonio Giordano, Priya U Kumthekar, Qingchun Jin, Busem Binboga Kurt, Siyang Ren, Tianyu Li, Jose Pablo Leone, Elizabeth A Mittendorf, Alyssa M Pereslete, Laura Sharp, Raechel Davis, Molly DiLullo, Nabihah Tayob, Erica L Mayer, Eric P Winer, Sara M Tolaney, Nancy U Lin\",\"doi\":\"10.1158/1078-0432.CCR-24-1161\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response.</p><p><strong>Patients and methods: </strong>This was a single-arm, multicenter, phase II trial of atezolizumab, pertuzumab, and high-dose trastuzumab for patients with HER2-positive breast cancer brain metastases. Participants received atezolizumab 1,200 mg i.v. every 3 weeks, pertuzumab (loading dosage 840 mg i.v., then 420 mg i.v. every 3 weeks), and high-dose trastuzumab (6 mg/kg i.v. weekly for 24 weeks, then 6 mg/kg i.v. every 3 weeks). The primary endpoint was CNS overall response rate per Response Assessment in Neuro-Oncology Brain Metastases criteria. Key secondary endpoints included CBR, overall survival, and safety and tolerability of the combination.</p><p><strong>Results: </strong>Among 19 enrolled participants, two had a confirmed intracranial partial response for a CNS overall response rate of 10.5% (90% confidence interval, 1.9%-29.6%). The study did not meet the prespecified efficacy threshold and was terminated early. The CBR was 42.1% at 18 weeks and 31.6% at 24 weeks. Seven patients (36.8%) required a dose delay or hold, and the most frequent any-grade adverse events were diarrhea (26.3%) and fatigue (26.3%).</p><p><strong>Conclusions: </strong>The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive breast cancer brain metastases.</p>\",\"PeriodicalId\":10279,\"journal\":{\"name\":\"Clinical Cancer Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.0000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528201/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Cancer Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1158/1078-0432.CCR-24-1161\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1078-0432.CCR-24-1161","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer.
Purpose: Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response.
Patients and methods: This was a single-arm, multicenter, phase II trial of atezolizumab, pertuzumab, and high-dose trastuzumab for patients with HER2-positive breast cancer brain metastases. Participants received atezolizumab 1,200 mg i.v. every 3 weeks, pertuzumab (loading dosage 840 mg i.v., then 420 mg i.v. every 3 weeks), and high-dose trastuzumab (6 mg/kg i.v. weekly for 24 weeks, then 6 mg/kg i.v. every 3 weeks). The primary endpoint was CNS overall response rate per Response Assessment in Neuro-Oncology Brain Metastases criteria. Key secondary endpoints included CBR, overall survival, and safety and tolerability of the combination.
Results: Among 19 enrolled participants, two had a confirmed intracranial partial response for a CNS overall response rate of 10.5% (90% confidence interval, 1.9%-29.6%). The study did not meet the prespecified efficacy threshold and was terminated early. The CBR was 42.1% at 18 weeks and 31.6% at 24 weeks. Seven patients (36.8%) required a dose delay or hold, and the most frequent any-grade adverse events were diarrhea (26.3%) and fatigue (26.3%).
Conclusions: The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive breast cancer brain metastases.
期刊介绍:
Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.