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

• DOI: 10.1200/jco.2008.26.15_suppl.1015
• Publication Date: 2017-02-24T07:33:44Z
• Authors: J. O'Shaughnessy; K. L. Blackwell; H. Burstein; A. M. Storniolo; G. Sledge; J. Baselga; M. Koehler; S. Laabs; A. Florance; D. Roychowdhury
• Keywords: Lapatinib; Clinical endpoint; Taxane

1015 Background: Lapatinib (L) is an oral, small-molecule inhibitor of EGFR and HER2 with a mechanism action distinct from that trastuzumab (T). Preclinical data suggest synergy between L T. We studied alone in combination T pts HER2+ MBC who progressed on Methods: Eligible women had received prior anthracycline taxane therapy, measurable lesions or bone-only disease, T-containing therapy. Pts were stratified by hormone receptor status visceral/nonvisceral then randomized to receive either (1,500 mg QD) (1,000 plus (2 mg/kg weekly after 4 loading dose). If the arm, they could cross over L+T arm. The primary endpoint was PFS (investigator assessment), secondary endpoints clinical benefit rate (CBR) at 24 wks, RR, OS. Results: 296 randomized. All T; median number chemotherapy regimens 6. Combination therapy significantly improved CBR; RR OS similar both arms (Table). Both treatment generally well tolerated. Grade 1/2 diarrhea higher arm (53% vs 41%); acneiform rash more common L-alone likely due dose. Asymptomatic decline LVEF (> 20% below LLN) occurred 5% 2% 1 death cardiac toxicity Conclusions: This largest study 2 targeted agents first demonstrate phase III setting. Improved outcome achieved progressing T-based without substantial change side effect profile. role combined anti-HER2 chemotherapy, less heavily pretreated patients early stage disease ongoing ALTTO (Adjuvant and/or Treatment Optimization) study. Endpoint + Hazard/OR 95% CI P value (median, wks) * 8.4 12.0 0.77 0.6, 1.0 0.029 CBR (%) 13.2 25.2 2.1 1.1, 4.2 0.020 6.9 10.3 1.5 3.9 0.46 39 51.6 0.75 0.5, 1.1 0.106 Intent treat. Author Disclosure Employment Leadership Consultant Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline Exelixis,