dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Cortés Castan, Javier |
dc.contributor.author | Provencher, Louise |
dc.contributor.author | Miller, Kathy |
dc.contributor.author | Chien, A. Jo |
dc.contributor.author | Rugo, Hope |
dc.contributor.author | Wardley, Andrew |
dc.date.accessioned | 2021-06-30T12:25:24Z |
dc.date.available | 2021-06-30T12:25:24Z |
dc.date.issued | 2021-05 |
dc.identifier.citation | Wardley A, Cortes J, Provencher L, Miller K, Chien AJ, Rugo HS, et al. The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer. Breast Cancer Res Treat. 2021 May;187:155-165. |
dc.identifier.issn | 1573-7217 |
dc.identifier.uri | https://hdl.handle.net/11351/6111 |
dc.description | Androgen receptor; HER2; Metastatic breast cancer |
dc.description.abstract | Purpose
Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab.
Methods
Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 anti-HER2 regimen for advanced disease. Patients received 160 mg oral enzalutamide daily and 6 mg/kg intravenous trastuzumab every 21 days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24 weeks (CBR24); secondary end points included progression-free survival (PFS) and safety.
Results
Overall, 103 women were enrolled [median age 60 years (range 34–83)]; 62% had received ≥ 3 lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24 weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4 months (95% confidence interval 2.0–3.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade ≥ 3 reported in ≥ 3 patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs.
Conclusions
Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination. |
dc.language.iso | eng |
dc.publisher | Springer |
dc.relation.ispartofseries | Breast Cancer Research and Treatment volume;187 |
dc.rights | Attribution 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.source | Scientia |
dc.subject | Medicaments antineoplàstics - Eficàcia |
dc.subject | Mama - Càncer - Quimioteràpia |
dc.subject.mesh | Breast Neoplasms |
dc.subject.mesh | Drug Therapy, Combination |
dc.subject.mesh | Efficacy |
dc.title | The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1007/s10549-021-06109-7 |
dc.subject.decs | neoplasias de la mama |
dc.subject.decs | farmacoterapia combinada |
dc.subject.decs | eficacia |
dc.relation.publishversion | https://link.springer.com/article/10.1007/s10549-021-06109-7 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut Català de la Salut |
dc.contributor.authoraffiliation | [Wardley A] NIHR Manchester Clinical Research Facility at The Christie NHS Foundation Trust and Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine, and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. [Cortes J] Division of Breast Cancers and Gynecological Tumors, IOB Institute of Oncology, Quironsalud Group, Madrid and Barcelona, Spain. Breast Cancer & Melanoma Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Provencher L] Department of Surgery, Centre des Maladies du Sein, CHU de Québec-Université Laval, Québec, Canada. [Miller K] Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, USA. [Chien AJ, Rugo HS] UCSF Comprehensive Cancer Center, University of California, San Francisco, USA |
dc.identifier.pmid | 33591468 |
dc.identifier.wos | 000618588100002 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |