Rethinking Initial Management of Patients With Brain Metastasis and HER2 Breast Cancer

“Treatment with lapatinib and capecitabine as initial therapy in an attempt to delay whole brain radiation (WBR) is a reasonable approach in a well-informed patient with brain metastasis and HER2+ breast cancer” said Nancy U. Lin, MD, regarding data from the LANDSCAPE trial presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) meeting.

“With an incidence of 30%-40%, central nervous system (CNS) metastases are common complications of HER2+ metastatic breast cancer, and the current standard practice is WBR. The whole brain irradiation can lead to neurological toxicity, and systemic treatments are universally held off during the time of WBR, and thus the frequently concomitant extra-CNS disease can worsen during this time," said Lin, who is an assistant professor of medicine at Harvard Medical School and holds active staff privileges at the Dana Farber Cancer Institute, Boston, Massachusetts.

As responses on CNS localization have been reported with the lapatinib + capecitabine combination after WBR, the LANDSCAPE trial evaluated this combination as first-line treatment for brain metastases in HER2+ metastatic breast cancer. "The aim to avoid or delay WBR, as well as provide an opportunity to treat both the CNS and the extra-CNS disease at the same time” said Thomas D. Bachelot, MD, PhD, the lead investigator of the LANDSCAPE trial, and an oncologist from Centre Léon Bérard, Lyon, France.

Patients in the LANDSCAPE trial were treated with 1250 mg of lapatinib/day combined with 2000 mg/m²/day of capecitabine days 1-14, every 21 days. The ASCO presentation detailed a remarkable CNS overall response rate of 67% among 43 efficacy-evaluable patients. Twenty one percent of patients had more than an 80% reduction in the size of CNS lesions, and 43% of patients also had a RECIST response in their extra-CNS disease. The median time to progression and median time to WBR were 5.5 months and 8.6 months, respectively. Additionally, the median survival had not been reached with a median follow-up of 14.1 months, with a 6-month survival of more than 90%, and 1-year survival of more than 70%.

Bachelot concluded that the combination has high activity in the initial treatment of patients with brain metastasis and HER2+ breast cancer, but needs to be further evaluated in phase III studies.

Lin said caveats of the trial were that, even though the inclusion criterion allowed patients with ECOG PS 0-2, approximately 5% of patients had an ECOG PS of 2, and thus this study was largely limited to patients with good performance status. Lin also commented that the treatment with lapatinib + capecitabine is associated with its own toxicities, including approximately 20% incidence of grade 3/4 diarrhea and another 20% incidence of grade 3/4 hand-foot syndrome. Nevertheless, Lin agreed that the combination has value in the management of patients with CNS metastasis in HER2+ breast cancer and may have the promise to reserve WBR in the future in a salvage setting.

Bachelot TD, Romieu G, Campone M, et al.LANDSCAPE: An FNCLCC phase II study with lapatinib (L) and capecitabine (C) in patients with brain metastases (BM) from HER2-positive (+) metastatic breast cancer (MBC) before whole-brain radiotherapy (WBR). J Clin Oncol. 2011. (suppl; abstr 509).