FROM THE LITERATURE

Dual TKIs and HER-2 Negative Breast Cancer

Lapatinib(Tykerb^®/Tyverb^®), a dual tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER-2/ErbB2), is effective against HER-2 positive locally advanced or metastatic breast cancer (MBC). But what about lapatinib activity in HER-2 negative and HER-2–uncharacterized (untested) MBC? A phase III randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for MBC evaluated the efficacy of lapatinib in HER-2 negative MBC. A preplanned retrospective evaluation of HER-2 status was performed. The primary endpoint was time to progression (TTP); secondary endpoints were ORR, clinical benefit rate (CBR), event-free survival (EFS), and OS. Results: In the ITT population (N=579) there were no significant differences in TTP, EFS, or OS between treatment arms. In 86 HER-2 (+) patients (15%), the paclitaxel-lapatanib arm resulted in statistically significant improvement in TTP, EFP, ORR, and CBR compared with paclitaxel-placebo. No differences between treatment groups were observed for any endpoint in HER-2 negative patients. Conclusion: Patients with HER-2 negative or HER-2 untested MBC did not benefit from the addition of lapatinib to paclitaxel, but the first-line therapy with paclitaxel-lapatinib significantly improved clinical outcomes in HER-2 positive patients. Phase II and III studies of lapatinib plus taxanes are ongoing in patients with HER-2 positive MBC.

JCO Early Release, published online ahead of print on October 27, 2008.

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