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Published on: August 2, 2022
Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer
Nancy U Lin1, Véronique Diéras, Devchand Paul
1Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Purpose:
Brain metastases develop in one third of patients with advanced HER2+ breast cancer. Effective therapy for patients with central nervous system (CNS) progression after cranial radiation is extremely limited and represents a major clinical challenge. Lapatinib, an epidermal growth factor receptor/HER2 inhibitor, was associated with regressions of CNS lesions in a small phase 2 trial. The current study was done to further evaluate the CNS activity of lapatinib. The study was later amended to allow patients who progressed on lapatinib the option of receiving lapatinib plus capecitabine.
Experimental Design:
Eligible patients had HER2+ breast cancer, progressive brain metastases, prior trastuzumab, and cranial radiotherapy. The primary end point was CNS objective response, defined as >or=50% volumetric reduction of CNS lesion(s) in the absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease.
Results:
Two-hundred and forty-two patients entered the study. CNS objective responses to lapatinib were observed in 6% of patients. In an exploratory analysis, 21% of patients experienced a >or=20% volumetric reduction in their CNS lesions. An association was observed between volumetric reduction and improvement in progression-free survival and neurologic signs and symptoms. Of the 50 evaluable patients who entered the lapatinib plus capecitabine extension, 20% experienced a CNS objective response and 40% experienced a >or=20% volumetric reduction in their CNS lesions.
Conclusions:
This study confirms the modest CNS antitumor activity of lapatinib. Additional responses were observed with the combination of lapatinib and capecitabine. Further studies of lapatinib-based regimens for CNS metastases from HER2+ breast cancer are warranted.
Insights
Lapatinib showed modest central nervous system (CNS) antitumor activity in patients with HER2+ breast cancer brain metastases. Combining lapatinib with capecitabine demonstrated additional responses, warranting further investigation.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Brain metastases are common in advanced HER2+ breast cancer, posing a significant treatment challenge, especially after cranial radiation.
- Effective therapies for central nervous system (CNS) progression are limited, highlighting the need for novel treatment strategies.
Purpose of the Study:
- To evaluate the CNS activity of lapatinib in patients with HER2-positive breast cancer and brain metastases.
- To assess the efficacy of lapatinib monotherapy and its combination with capecitabine in patients with CNS progression.
Main Methods:
- A study involving patients with HER2+ breast cancer, progressive brain metastases, prior trastuzumab, and cranial radiotherapy.
- The primary endpoint was CNS objective response, defined by a significant volumetric reduction in CNS lesions without disease progression.
Main Results:
- Lapatinib monotherapy resulted in CNS objective responses in 6% of patients, with 21% showing a >=20% volumetric reduction.
- The combination of lapatinib plus capecitabine showed higher response rates, with 20% objective response and 40% >=20% volumetric reduction in evaluable patients.
- Volumetric reduction correlated with improved progression-free survival and neurological symptoms.
Conclusions:
- Lapatinib exhibits modest CNS antitumor activity in HER2+ breast cancer brain metastases.
- The combination of lapatinib and capecitabine offers potential for enhanced efficacy in this patient population.
- Further research into lapatinib-based regimens for CNS metastases is recommended.
