Neoadjuvant Combination Therapy for HER2-Positive Primary Breast Cancer
The NeoPHOEBE trial, which tested neoadjuvant buparlisib or placebo plus trastuzumab followed by buparlisib or placebo with trastuzumab and paclitaxel, was suspended early, largely because of liver toxicity. However, the investigators say the results suggest phosphatidylinositol 3-kinase (PI3K)-targeted therapy may be useful in this setting, and second-generation PIK3 inhibitors may be better tolerated. Professor Sibylle Loibl, of the German Breast Group, Neu-Isenburg, Germany, and colleagues reported their findings in the European Journal of Cancer.
Patient recruitment was stopped after 50 of the planned 256 patients were enrolled, mainly because of liver toxicity. Of the 25 patients treated with buparlisib, 21 had wild-type PIK3CA mutation and 4 had mutant PIK3CA. Before the trial was suspended there was a trend toward higher overall response and a significant decrease in Ki67 with buparlisib versus placebo in the estrogen receptor–positive subgroup.
“Analysis of biomarker data from recent trials evaluating agents targeting the PI3K/AKT/mTOR pathway and those targeting HER2 may provide insights into identifying the subset of population which would benefit from a combination of a PI3K inhibitor and a HER2-targeted agent,” suggested the investigators.