Afatinib With CT and RT for EGFR-Mutant NSCLC

Study treatment will be divided into 5 stages:

Stage 1-induction, consisting of afatinib for two 4-week cycles. Afatinib is a pill that the patient takes by mouth once per day. The patient will receive a study drug diary in which to record the doses of afatinib.

Stage 2-concurrent radiation and chemotherapy with cisplatin/pemetrexed for two 3-week cycles.

Stage 3-Surgery to remove tumor for participants whose tumor can be removed by surgery. This will be done about 4-6 weeks after finishing radiation and chemotherapy. The exact timing will depend upon how quickly the patient recovers from side effects of the radiation and chemotherapy. The investigators will use a piece of the patients tumor removed by surgery for research tests to look for biomarkers such as genes and proteins that may be associated with response to afatinib, chemotherapy or radiation.

Stage 4-Chemotherapy after surgery (adjuvant chemotherapy). The patients doctor will decide if the patient will receive chemotherapy after the patients surgery but before receiving consolidation with afatinib. If the patient does receive this, it will start 6-12 weeks after surgery or finishing radiation if the patient does not have surgery. The chemotherapy will be the same as that received along with the radiation therapy.

Stage 5-Consolidation with afatinib for twenty-six 4-week cycles (2 years) for participants who responded to the 2 cycles of induction afatinib.

The investigators would like to keep track of the patients medical condition and status of the patients disease for up to 5 years after the patient stops study treatment. Keeping in touch with the patients and checking on the patients condition every year helps the investigators look at the long-term effects of the research study. The patients will be asked to have CT scans as follows:

• Every 3 months for the first year after stopping study treatment
• Every 6 months for years 2-4 after stopping study treatment
• Once per year in year 5 after stopping study treatment

Inclusion criteria

• Histologically confirmed stage IIIA NSCLC
• Measurable disease
• Have lung cancer harboring an EGFR mutation
• Must be evaluated by a medical oncologist, radiation oncologist and thoracic surgeon within 4 weeks of enrollment into study to document that they are a candidate for chemoradiation and for consideration of surgical resection (not required to be a surgical candidate)

Exclusion criteria

• Pregnant or breastfeeding
• Prior EGFR TKI therapy
• Prior treatment with radiation to the thoracic region (including breast irradiation)
• Known pre-existing interstitial lung disease
• Significant or recent gastrointestinal disorders with diarrhea as a major symptom
• History or presence of relevant cardiovascular abnormalities
• Any other concomitant serious illness or organ system dysfunction
• Active hepatitis B, C or known HIV carrier
• Known or suspected active drug or alcohol use
• Known hypersensitivity to afatinib, cisplatin, or pemetrexed
• Concomitant treatment with strong inhibitor of P-gp
• History of an active malignancy within the last 3 years