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)-Reference-Cited by-同舟云学术

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)

Published:2018-01 Issue: Volume:10 Page:175883591880733
ISSN:1758-8359
Container-title:Therapeutic Advances in Medical Oncology
language:en
Short-container-title:Ther Adv Med Oncol

Author:

Hurvitz Sara¹,Singh Rashi²,Adams Brad³,Taguchi Julie A.⁴,Chan David⁵,Dichmann Robert A.⁶,Castrellon Aurelio⁷⁸,Hu Eddie³,Berkowitz Jonathan⁶,Mani Aruna⁷⁸,DiCarlo Brian⁹,Callahan Rena³,Smalberg Ira¹⁰,Wang Xiaoyan³,Meglar Ivana³,Martinez Diego³¹¹,Hobbs Evthokia³¹²,Slamon Dennis J.³

Affiliation:

1. University of California, Los Angeles, 10945 Le Conte Avenue, PVUB Suite 3360, Los Angeles, CA 90095, USA

2. University of California, Irvine, Irvine, CA, USA

3. University of California, Los Angeles, Los Angeles, CA, USA

4. Ridley-Tree Cancer Center, Santa Barbara, CA, USA

5. Torrance Health Association DBA, Torrance Memorial Physician Network, Redondo Beach, CA, USA

6. Central Coast Medical Oncology Corporation, Santa Maria, CA, USA

7. Memorial Healthcare System, Hollywood, FL, USA

8. Current address: Genentech, San Francisco, CA, USA

9. San Luis Obispo Oncology and Hematology Health Center, San Luis Obispo, CA, USA Coastal Integrative Cancer Care, San Luis Obispo, CA

10. Tower Imaging Medical Group, Los Angeles, CA Tower Saint John’s Imaging, Santa Monica, CA, USA

11. Current address: Science 37, Los Angeles, CA, USA

12. Current address: Oregon Health and Science University (OHSU), Portland, OR, USA

Abstract

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

Funder

GlaxoSmithKline

National Cancer Institute/National Institute of Health

Novartis Pharmaceuticals Corporation

Publisher

SAGE Publications

Subject

Oncology

Link

http://journals.sagepub.com/doi/pdf/10.1177/1758835918807339

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