SIDEBAR: Does Lapatinib Prevent CNS Metastases in HER2-positive Breast Cancer?

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Lapatinib has shown some efficacy against existing brain metastases in patients with HER2-positive breast cancer but not in preventing them in the first place, according to Hope S. Rugo, MD, Professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center.

In a trial comparing lapatinib (Tykerb)/capecitabine (Xeloda) vs capecitabine alone, the first site of progression was less frequently the brain in the group receiving the combination, she noted.1 “But over the course of following those patients for progression, there was an identical number of brain metastases in both arms.”

And the MA.31 trial comparing trastuzumab (Herceptin) and lapatinib is tracking the incidence of brain metastases as a secondary endpoint.2 “So far, there has been absolutely no difference,” she commented.

“So at the present time, there would be no indication to use lapatinib for prevention of brain metastases, although clearly we have trials that indicate some response once you have existing brain metastases,” Dr. Rugo concluded. “We’ll get more information looking at the ALTTO trial,” which is comparing trastuzumab, sequential lapatinib, and trastuzumab, and the combination of lapatinib and trastuzumab in the adjuvant setting.3

Disclosure: Dr. Rugo has received research funding from Abraxis BioScience, Bristol-Myers Squibb, and Roche/Genentech.


1. Geyer CE, Forster J, Lindquist D, et al: Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733-2743, 2006.

2. Gelmon K, Boyle F, Kaufman B, et al: Open-label phase III randomized controlled trial comparing taxane-based chemotherapy with lapatininb or trastuzumab as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis of NCIC CTG MA.31/GSK EGF 108919. 2012 ASCO Annual Meeting. Abstract LBA671. Presented June 3, 2012.

3. ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) Study; BIG 2-06/N063D. Last updated August 23, 2012. Available at Accessed September 2, 2012.

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