Cutaneous metastases in breast cancer are a common and very morbid development in women with metastatic breast cancer (MBC). Skin metastases have been estimated to develop in 24% of patients with MBC, maybe even higher if Her2 overexpressing. It has been hypothesized that skin may represent a sanctuary site, like CNS, for Her2+ patients (pts). Case reports of patients developing skin only progression on anti-Her-2 antibody therapy have been reported.
This phase 1 study of ONT-380, a potent, oral selective small molecule inhibitor of HER2, dosed in 2 cohorts of 350mg PO BID (8 pts) and 300mg PO BID (52 pts) given with either C (1000mg/m2 PO BID 14 days of 21-day-cycle) or T (8mg/kg IV load; then 6mg/kg IV once every 21 days) or the triplet was conducted in women with Her2+ MBC previously treated with trastuzumab and T-DM1. Prior lapatinib, neratinib, and pertuzumab were allowed. Tumor response was assessed by RECIST 1.1. Sixty patients were treated on study and 27 received the triplet of ONT-380 with C and T. Eight patients had skin noted as a site of disease.
Skin was a measurable site of disease in 6 women and non-measurable site in 2 women. In all 8 women there were clinical responses in the skin with ONT-380 and C (2 pts), ONT-380 with T (1 pt) or ONT-380 with C plus T (5 pts). Two women had complete response of their skin disease, 3 had partial response (PR) and 3 had regressions that did not meet criteria for PR. All but one woman had prior lapatinib therapy and all but one woman had prior radiation to the skin and chest wall. Median time on therapy was 8.5 cycles (5-13 range). One patient is still on study.
We report on 8 patients with significant response in skin as a disease site while on ONT-380 with either C or T or the combination. ONT-380 shows evidence of efficacy in cutaneous metastases, a common and difficult site of disease to control for women with Her2+ MBC.
Clinical trial identification
Legal entity responsible for the study
L.N. Walker: I am an employee of Oncothyreon, Inc.
S.L. Moulder: My only disclosures are to be a non-compensated advisor to Oncothyreon and to have received funding to support the clinical trial including effort as PI.
All other authors have declared no conflicts of interest.