Randomized phase II trial of capecitabine and lapatinib with or without cixutumumab in patients with HER2+ breast cancer previously treated with trastuzumab and an anthracycline and/or a taxane: NCCTG N0733 (Alliance).

• DOI: 10.1200/jco.2014.32.15_suppl.632
• Publication Date: 2019-01-03T22:24:56Z
• Authors: Paul Haluska; Albert M. Bernath; Karla V. Ballman; Amylou C. Dueck; Hannah M. Linden; Matthew P. Goetz; Donald W. Northfelt; Xiaonan Hou; Kathleen S. Tenner; Piyawan Tienchaia...; Lynn M. Flickinger; Beiyun Chen; Helen X. Chen; Wilma L. Lingle; Christine M. Pell...; Robert W. Sponzo; Monica Madden Rei...; Edith A. Perez
• Keywords: Lapatinib; Tolerability; Clinical endpoint; Taxane

632 Background: Crosstalk between the insulin-like growth factor (IGF) and HER2 pathways in multiple preclinical models suggest a mechanism of resistance to HER2-targeted therapy. Cixutumumab (CIX, IMC-A12), an anti-IGF-1 Receptor monoclonal antibody, was investigated combination with capecitabine lapatinib (cape/lap) determine if addition IGF target agent would improve PFS compared cape/lap unselected HER2+ metastatic breast cancer (mbc) patients (pts). binding protein (IGFBP) levels may be important predicting tumor dependence on signaling are potential biomarkers. Methods: Following initial safety cohort, this open label phase II study randomized (2:1) pts CIX (Arm B) or A). Primary endpoint progression-free survival (PFS) 144 planned for hazard ratio 0.56. estimated using Kaplan-Meier Cox regression. Secondary endpoints included assessing overall treatment tolerability. Correlative studies assessments IGFBPs 1-6 Luminex multiplex assay pt serum. Results: 64 evaluable were accrued, including 8 cohort. The most common grade 3 events diarrhea, fatigue mucositis. Dose reductions cohort 6 prompted dose reduction Arm B portion. portion closed early at 56 due slow accrual. Median by A 6.0 mo vs. 4.9 (p= 0.89). (16.8 vs 14.7 mo, p=0.93), time failure (TTF) (4.6 4.4 p=0.66), duration response (4.8 6.9 p=0.26) not different arms. In B, increase IGFBP5 correlated poor (1.4 9.9 p= 0.02) high improved TTF (9.9 3.9 0.03). Conclusions: is reasonably tolerated following reduction, but does mbc. determinant benefit from targeted therapy warrants further investigation. Clinical trial information: NCT00684983.