A Phase II Evaluation of Afatinib

Primary objective

1. To assess the activity of afatinib in patients with persistent or recurrent USC overexpressing HER2/neu with the frequency of patients who survive progression-free for at least 6 months after initiating therapy. b.

Secondary objectives

1. To assess objective response rate (ORR) and durable disease control rate (DDCR),
2. To assess overall survival (OS)
3. To assess the safety profile of afatinib in USC patients

Exploratory/correlative objectives

1. To systematically evaluate HER2/neu expression/amplification using standardized scoring criteria for both breast and gastric cancer and correlate clinical response in EC patients with HER2/neu scoring results.
2. To correlate ORR, PFS, and OS with the presence/absence of PIK3CA (phosphatidyl inositol 3-kinase catalytic subunit) and FBXW7 (F-box/WD repeat-containing protein) mutations by standard Sanger sequencing, and presence/absence of Cyclin E2 overexpression by IHC in endometrial cancer patients overexpressing HER2/neu treated with Afatinib

To study:

1. HER2/neu extracellular domain (ECD) circulating levels in the plasma of USC patients overexpressing HER2/neu before, and during Afatinib treatment to elucidate whether changes in HER2/neu ECD would predict response to Afatinib and
2. To determine peripheral blood natural killer (NK) cell numbers and activity in HER2/neu+ USC patients before, and during Afatinib treatment to assess the possible therapeutic contributions of immune mechanisms of action of Afatinib.