A phase II trial of trabectedin in triple-negative and HER2-overexpressing metastatic breast cancer

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• 作者：Joanne L. Blum ; Anthony Gonçalves ; Noa Efrat…
• 关键词：Trabectedin ; Breast cancer ; HER2 ; Triple negative
• 刊名：Breast Cancer Research and Treatment
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：155
• 期：2
• 页码：295-302
• 全文大小：516 KB
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• 作者单位：Joanne L. Blum (1)
  Anthony Gonçalves (2)
  Noa Efrat (3)
  Marc Debled (4)
  Pierfranco Conte (5) (6)
  Paul D. Richards (7)
  Donald Richards (8)
  Pilar Lardelli (9)
  Antonio Nieto (9)
  Martin Cullell-Young (9)
  Suzette Delaloge (10)
  
  1. Baylor-Charles A. Sammons Cancer Center, Texas Oncology, US Oncology, 3410 Worth St., Suite 400, Dallas, TX, 75246, USA
  2. Institut Paoli Calmettes, Marseille, France
  3. Kaplan Medical Center, Rehovot, Israel
  4. Institute Bergonie, Bordeaux, France
  5. Azienda Ospedaliero, Università di Modena, Modena, Italy
  6. Istituto Oncologico Veneto, IRCCS, Università di Padova, Padua, Italy
  7. Oncology/Hematology Associates of SW Virginia, US Oncology, Salem, VA, USA
  8. Texas Oncology - Tyler, US Oncology, Tyler, TX, USA
  9. Pharma Mar, S.A., Clinical R&D, Colmenar Viejo, Madrid, Spain
  10. Gustave Roussy Cancer Campus, Villejuif, France
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

Trabectedin is an alkylating agent that binds to the minor groove of DNA. Early studies with trabectedin suggested efficacy in triple-negative and HER2-overexpressing metastatic breast cancer (MBC). The efficacy and safety of trabectedin in pretreated patients with these tumors were evaluated in this parallel-cohort phase II trial. Patients received a 3-h infusion of trabectedin 1.3 mg/m2 intravenously every 3 weeks until progression or unmanageable/unacceptable toxicity. The primary objective was to evaluate the efficacy using the objective response rate (ORR) as per Response Evaluation Criteria In Solid Tumors (RECIST). Secondary objectives comprised time-to-event endpoints and safety assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.3.0. Patients with heavily pretreated triple-negative (n = 50) or HER2-overexpressing (n = 37) MBC were enrolled. No confirmed responses were found in triple-negative MBC patients, with median progression-free survival (PFS) of 2.2 months (95 % CI 1.3–2.7 months). Confirmed partial responses occurred in 4 of 34 evaluable HER2-overexpressing MBC patients (ORR = 12 %; 95 % CI 3–27 %) and lasted a median of 12.5 months (95 % CI, 6.2–14.7 months); median PFS was 3.8 months (95 % CI, 1.8–5.5 months). Most trabectedin-related adverse events were mild or moderate, and the most frequent were fatigue, nausea, vomiting, constipation, and anorexia. Severe neutropenia and transaminase increases were non-cumulative and transient and were mostly managed by infusion delays or dose reductions. Single-agent trabectedin is well tolerated in aggressive MBC and has moderate activity in HER2-overexpressing tumors. Further studies are warranted to evaluate trabectedin combined with HER2-targeted treatments in this subtype. Keywords Trabectedin Breast cancer HER2 Triple negative