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Phase Ib/II single-arm trial evaluating the combination of everolimus, lapatinib and capecitabine for the treatment of HER2-positive breast cancer with brain metastases (TRIO-US B-09).
Hurvitz, Sara; Singh, Rashi; Adams, Brad; Taguchi, Julie A; Chan, David; Dichmann, Robert A; Castrellon, Aurelio; Hu, Eddie; Berkowitz, Jonathan; Mani, Aruna; DiCarlo, Brian; Callahan, Rena; Smalberg, Ira; Wang, Xiaoyan; Meglar, Ivana; Martinez, Diego; Hobbs, Evthokia; Slamon, Dennis J.
Afiliação
  • Hurvitz S; University of California, Los Angeles, 10945 Le Conte Avenue, PVUB Suite 3360, Los Angeles, CA 90095, USA.
  • Singh R; University of California, Irvine, Irvine, CA, USA.
  • Adams B; University of California, Los Angeles, Los Angeles, CA, USA.
  • Taguchi JA; Ridley-Tree Cancer Center, Santa Barbara, CA, USA.
  • Chan D; Torrance Health Association DBA, Torrance Memorial Physician Network, Redondo Beach, CA, USA.
  • Dichmann RA; Central Coast Medical Oncology Corporation, Santa Maria, CA, USA.
  • Castrellon A; Memorial Healthcare System, Hollywood, FL, USA.
  • Hu E; University of California, Los Angeles, Los Angeles, CA, USA.
  • Berkowitz J; Central Coast Medical Oncology Corporation, Santa Maria, CA, USA.
  • Mani A; Memorial Healthcare System, Hollywood, FL, USA.
  • DiCarlo B; San Luis Obispo Oncology and Hematology Health Center, San Luis Obispo, CA, USA Coastal Integrative Cancer Care, San Luis Obispo, CA.
  • Callahan R; University of California, Los Angeles, Los Angeles, CA, USA.
  • Smalberg I; Tower Imaging Medical Group, Los Angeles, CA Tower Saint John's Imaging, Santa Monica, CA, USA.
  • Wang X; University of California, Los Angeles, Los Angeles, CA, USA.
  • Meglar I; University of California, Los Angeles, Los Angeles, CA, USA.
  • Martinez D; University of California, Los Angeles, Los Angeles, CA, USA.
  • Hobbs E; University of California, Los Angeles, Los Angeles, CA, USA.
  • Slamon DJ; University of California, Los Angeles, Los Angeles, CA, USA.
Ther Adv Med Oncol ; 10: 1758835918807339, 2018.
Article em En | MEDLINE | ID: mdl-30542377
BACKGROUND: Improving outcomes for patients with human epidermal growth factor 2-positive (HER2+) central nervous system (CNS) metastases remains an unmet clinical need. This trial evaluated a novel combination of everolimus, lapatinib and capecitabine for this disease. METHODS: Patients with trastuzumab-pretreated, HER2+ breast cancer brain metastasis without prior therapy with a mammalian target of rapamycin (mTOR) inhibitor were eligible. Patients received lapatinib and everolimus daily (continuously) and capecitabine twice daily (d1-14) in 21-d cycles. The primary endpoint was the 12-week CNS objective response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), best CNS ORR and extra-CNS ORR. RESULTS: A total of 19 participants were enrolled and treated with ⩾1 dose of the study drug. The median age was 58.5 years, the median number of therapies for metastatic breast cancer was 2.5 (0-11). Pretrial, 74% of participants had received prior lapatinib, capecitabine or both. A total of 63% had received previous CNS radiation or surgical resection and CNS radiation. The maximum tolerated doses were lapatinib at 1000 mg, everolimus at 10 mg, and capecitabine at 1000 mg/m2. Phase II proceeded with capecitabine at 750 mg/m2 due to better tolerability. The most common grade 3/4 adverse events were mucositis (16%), diarrhea, fatigue, and hypokalemia (11% each). Of 11 participants evaluable for 12-week CNS ORR, 3 (27%) had partial response and 7 (64%) had stable disease. The best CNS ORR in eligible participants was 28% (5/18). The median PFS and OS were 6.2 and 24.2 months, respectively. CONCLUSIONS: This novel triplet combination of lapatinib, everolimus, and capecitabine is well tolerated and yielded a 27% response rate in the CNS at 12 weeks in heavily pretreated participants. Larger studies are warranted to further evaluate this regimen. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01783756. Registered 05 February 2013, https://clinicaltrials.gov/ct2/show/NCT01783756.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Ther Adv Med Oncol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Ther Adv Med Oncol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos