Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 1015
© 2008 American Society of Clinical Oncology

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Abstract

A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy

Baylor Sammons Cancer Center, Dallas, TX; Duke University Medical Center, Raleigh, NC; Dana-Farber Cancer Institute, Boston, MA; Indiana University Cancer Center, Indianapolis, IN; Vall d'Hebron University Hospital, Barcelona, Spain; GlaxoSmithKline, Collegeville, PA

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Background: Lapatinib (L) is an oral, small-molecule inhibitor of EGFR and HER2 with a mechanism of action distinct from that of trastuzumab (T). Preclinical data suggest synergy between L and T. We studied L alone and in combination with T in pts with HER2+ MBC who progressed on T. Methods: Eligible women had received prior anthracycline and taxane therapy, had MBC with measurable lesions or bone-only disease, and had progressed on prior T-containing therapy. Pts were stratified by hormone receptor status and visceral/nonvisceral disease, then randomized to receive either L (1,500 mg QD) or L (1,000 mg QD) plus T (2 mg/kg weekly after 4 mg/kg loading dose). If pts progressed on the L arm, they could cross over to the L+T arm. The primary endpoint was PFS (investigator assessment), and secondary endpoints were clinical benefit rate (CBR) at 24 wks, RR, and OS. Results: 296 pts were randomized. All pts had received prior T; the median number of prior chemotherapy regimens was 6. Combination therapy significantly improved PFS and CBR; RR and OS were similar in both arms (Table). Both treatment regimens were generally well tolerated. Grade 1/2 diarrhea was higher in the L+T arm (53% vs 41%); acneiform rash was more common in the L-alone arm, likely due to higher L dose. Asymptomatic decline in LVEF (> 20% and below LLN) occurred in 5% of pts in L+T arm and 2% of pts in L-alone arm. 1 death occurred due to cardiac toxicity in the L+T arm. Conclusions: This is the largest study of 2 targeted agents in HER2+ MBC and the first to demonstrate the synergy of L+T in a phase III setting. Improved clinical outcome was achieved with the combination of L+T in pts progressing on T-based therapy and without a substantial change in the side effect profile. The role of combined anti-HER2 therapy, in combination with chemotherapy, in less heavily pretreated patients with early stage disease is ongoing in the ALTTO (Adjuvant L and/or T Treatment Optimization) study.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline Exelixis, GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline

Abstract presentation from the 2008 ASCO Annual Meeting

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