Trastuzumab Remains ‘Standard of Care’ For HER2-Positive Metastatic Breast Cancer

Lapatinib–capecitabine fails to show greater efficacy than trastuzumab–capecitabine for the treatment of metastatic breast cancer

medwireNews: Trastuzumab -based chemotherapy should remain the standard of care for patients with HER2-positive, metastatic breast cancer (MBC), the CEREBEL investigators recommend.

Although lapatinib is thought to have some central nervous system (CNS) activity, unlike trastuzumab which is unable to cross the blood–brain barrier, the phase III trial failed to show a significant benefit for lapatinib–capecitabine over trastuzumab–capecitabine for women with pretreated HER2-positive MBC with regard to the primary endpoint, risk of CNS metastases as the first site of relapse.

CNS metastases were the first site of progression in 5% of the 250 patients in the modified intention-to-treat population who were randomly assigned to receive trastuzumab–capecitabine and 3% of the 251 patients given lapatinib–capectiabine, a nonsignificant difference.

Furthermore, analysis of secondary endpoints showed that the trastuzumab–capecitabine group had significantly better progression-free survival (median 8.1 vs 6.6 months; hazard ratio [HR]=1.30) and a trend towards better overall survival (median 27.3 vs 22.7 months; HR=1.34).

“CEREBEL confirms the use of lapatinib-capecitabine only after disease progression on a trastuzumab-based regimen for MBC”, say Xavier Pivot, from Centre Hospitalier Universitaire in Besançon, France, and co-authors.

“As the hierarchy of treatments for patients with HER2-positive MBC evolves, the availability of pertuzumab and trastuzumab emtansine will presumably modify the therapy for earlier lines of MBC. Thus, lapatinib-capecitabine may be used in the third-line setting”, they write in the Journal of Clinical Oncology.

The researchers note, however, that the study was significantly underpowered for the primary endpoint because CNS metastases occurred at a lower rate than expected, most likely because magnetic resonance imaging screening led to patients with asymptomatic CNS metastases being excluded from the study at baseline.

“These results suggest that patients in prospective randomized trials testing new agents with a well-known inability to cross the blood–brain barrier should undergo systematic baseline evaluation before enrollment to avoid possible bias in results”, the researchers suggest.

They continue: “[W]e acknowledge that routine screening for asymptomatic CNS lesions is controversial without knowledge of the proportion of patients who would eventually develop symptoms or would derive benefit from early intervention.

“In this context, a follow-up of patients from CEREBEL in whom asymptomatic CNS metastases were detected would provide valuable data regarding outcome of these patients.”


Pivot X, Manikhas A, Żurawski B,et al. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol 2015; Published online before print 20 January. doi: 10.1200/JCO.2014.57.1794

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