In a study reported in Clinical Cancer Research, Groeneweg and colleagues found that dual HER2 targeting showed greater activity than a single agent in HER2-amplified uterine serious carcinoma.
In the study, ARK1, ARK2, and SPEC2 cell lines were treated with trastuzumab (Herceptin) or lapatinib (Tykerb), and mice with xenografts derived from ARK2 and SPEC2 cell lines and EnCa1 and EnCa2 primary human tumor samples were treated with vehicle, trastuzumab, lapatinib, or the combination of trastuzumab and lapatinib.
Single-agent trastuzumab produced little effect in all models. Lapatinib reduced proliferation in all cell lines and inhibited growth of HER2-amplified ARK2 and EnCa1 xenografts. Dual therapy produced significant antitumor activity in ARK2 and EnCa1 xenografts. Overall, dual therapy induced alteration of downstream MAPK and PI3K pathway mediators only in HER2-amplified models and was associated with increased apoptosis and decreased proliferation.
The investigators concluded: “Although trastuzumab alone did not impact [uterine serous carcinoma] growth, dual anti-HER2 therapy with lapatinib led to improved inhibition of tumor growth in HER2-amplified [uterine serous carcinoma] and may be a promising avenue for future investigation.” ■
Groeneweg JW, et al: Clin Cancer Res 20:1-12, 2014.