Everolimus/Lapatinib/Capecitabine Is Effective and Safe for HER2+ Breast Cancer With Brain Metastases
TAKE-HOME MESSAGE
- Results of this study demonstrate the tolerability of the combination of everolimus, lapatinib, and capecitabine in heavily pretreated patients with HER2-positive disease and brain metastasis.
- Given the promising response rate (27% at 12 weeks), additional larger studies are warranted.
summary
This abstract is available on the publisher's site.
Access this abstract nowThis study evaluated the response of 19 patients pretreated with trastuzumab with HER2-positive breast cancer brain metastasis to at least 1 dose of the novel combination of everolimus, lapatinib, and capecitabine. The maximum tolerated doses were 1000 mg lapatinib, 10 mg everolimus, and 1000 mg/m2 capecitabine. The phase II trial continued with 750 mg/m2 capecitabine given better tolerability. Frequently reported grade 3/4 adverse events included mucositis, diarrhea, fatigue, and hypokalemia. Of 11 patients evaluable for the 12-week CNS objective response rate, 3 had achieved partial responses and 7 had stable disease. Median progression-free and overall survival were 6.2 months and 24.2 months, respectively.
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Additional Info
Disclosure statements are available on the authors' profiles:
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)
Ther Adv Med Oncol 2018 Dec 01;[EPub Ahead of Print], S Hurvitz, R Singh, B Adams, JA Taguchi, D Chan, RA Dichmann, A Castrellon, E Hu, J Berkowitz, A Mani, B DiCarlo, R Callahan, I Smalberg, X Wang, I Meglar, D Martinez, E Hobbs, DJ SlamonFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
These results sound promising; however, we need bigger numbers to have a better understanding of the adverse effects and the impact that the combination may have on CNS disease. Brain metastasis is one of the most frightening types of metastatic disease for women with stage IV breast cancer. The location and number of metastatic lesions in the brain may need to be factored into the selection process. We never want to give false hope to a patient who has extensive disease.
The development of HER2-targeted therapies has improved outcomes substantially. Unfortunately, the efficacy of many of these agents for the treatment of brain metastases is limited, and this remains an area of unmet need. In the current study, the addition of everolimus to capecitabine and lapatinib was investigated in patients who had HER2-positive metastatic breast cancer with progressive brain metastases. Patients were heavily pretreated, and many of them had already received lapatinib and capecitabine, but none had received prior everolimus. Although a very small study, the response rate of 27% was notable and the therapy was reasonably well-tolerated.
This is an area of active investigation, with many other studies ongoing. For example, we are awaiting the results of the NALA trial, which is a randomized phase III study comparing capecitabine plus neratinib with capecitabine plus lapatinib. Tucatinib has also shown promise in this area, demonstrating a 42% CNS response rate in a small phase I study in which it was administered with capecitabine and trastuzumab. The combination is being further investigated in the HER2CLIMB study in which patients are eligible with no, stable, or active brain metastases. Hopefully these studies will improve outcomes for this subset of breast cancer patients who are in desperate need.