Inclusion Criteria:

- Pathologically or cytologically MSKCC confirmed esophagogastric cancer.

- HER2 overexpression and/or amplification as determined by immunohistochemistry (3+)
or FISH (≥2.0)

- Previously received trastuzumab as part of a regimen in the perioperative or
metastatic setting with evidence of progression. Washout period for trastuzumab of 14
days.

- May have previously received lapatinib as part of a regimen in the perioperative or
metastatic setting with evidence of progression of disease. Washout period for
lapatinib of 14 days.

- Completion of previous chemotherapy regimen ≥2 weeks prior to the start of study
treatment.

Other chemotherapy regimens may have been administered between the time of progression on
prior trastuzumab containing regimen and protocol therapy. No restriction on prior
chemotherapy regimens for advanced stage disease.

- At least one measurable metastatic lesion according to RECIST 1.1 criteria. Ascites,
pleural effusions, and bone metastases are not considered measurable. Minimum
indicator lesion size = 10 mm by helical CT or = 20 mm by conventional techniques.
Pathological nodes must be = 15 mm by the short axis to be considered measurable.

- Patients aged 18 years or older, as no dosing or adverse event data are currently
available on the use of afatinib in patients <18 years of age, children are excluded
from this study.

- Life expectancy of at least three (3) months.

- Karnofsky performance status ≥60%

- All patients with disease technically amenable to biopsy will be asked to undergo a
biopsy. Patient must agree to allow 2 biopsies of any malignant lesion that can be
accessed by endoscopy or with the aid or radiology (i.e. CT guided).

- Patients who have previously provided samples at any time after trastuzumab
resistance will be exempt from biopsy at the start of therapy.

- Consent to preservation of frozen and fixed samples of tumor cores for evaluation

- Able to swallow and retain oral medication.

- Negative serum HCG pregnancy test for premenopausal women of reproductive capacity
and for women less than 12 months after menopause.

- Willingness to use birth control while on study.

- Asymptomatic, central nervous system metastases are permitted.

Exclusion Criteria:

- Patients receiving any concurrent anticancer therapy or investigational agents with
the intention of treating esophagogastric cancer.

- Patients who are unwilling to consent to tumor biopsy Women who are pregnant or
breast feeding.

- Concurrent radiotherapy is not permitted for disease progression on treatment on
protocol (except in the context specified in section 9.0), but might be allowed for
pre-existing non-target lesions with approval from the principal investigator of the
trial.

- Concurrent medical conditions which may increase the risk of toxicity, including
ongoing or active infection, history of significant bleeding disorder unrelated to
cancer (congenital bleeding disorders, acquired bleeding disorders within one year),
HIV-positive or active hepatitis.

History or presence of clinically relevant cardiovascular abnormalities such as
uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable
angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to
study entry.

- Baseline (< 1 month before treatment) cardiac left ventricular function with resting
ejection fraction of less than 50% measured by echocardiogram.

- Known pre-existing interstitial lung disease.

- Significant or recent acute gastrointestinal disorders with diarrhea as a major
symptom e.g., Crohn's disease, malabsorption, or CTCAE grade >2 diarrhea of any
etiology.

- Unwillingness to give written informed consent, unwillingness to participate, or
inability to comply with the protocol for the duration of the study.

- Active hepatitis B infection, active hepatitis C infection or known HIV carrier

- Known or suspected active drug or alcohol abuse. Restricted Therapies

- Additional experimental anti-cancer treatment and/or standard chemo-, immunotherapy,
hormone treatment (with the exception of megestrol acetate), or radiotherapy is not
allowed concomitantly with the administration of study treatment (with the exception
listed in section 9.0). Afatinib is a substrate of P-gp and its plasma
concentrations can be affected by the use of P-gp inhibitors (data on file) and it is
also likely that P-gp inducers could also influence afatinib plasma concentrations.

- The use of potent P-gp inhibitors (including cyclosporine, erythromycin,
ketoconazole, itraconazole, quinidine, Phenobarbital salt with quinidine, ritonavir,
valspodar, verapamil) and potent P-gp inducers (including St John's wort, rifampicin)
has to be avoided during treatment with afatinib. Any exemptions to this have to be
discussed with the principal investigator.