Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation

Inclusion Criteria:

* Unresectable or inoperable, stage III or locoregional recurrence without evidence of distant, metastatic disease
* Pathologic confirmation of NSCLC at MSKCC
* Documentation of a sensitizing EGFR mutation
* Age ≥ 18 years
* No contraindication to definitive thoracic radiation therapy with concurrent chemotherapy

Adequate organ function as defined by:

* Calculated creatinine clearance≥ 45 mL/min (by Cockcroft-Gault)
* Total bilirubin less than 1.5 x ULN (unless known Gilbert's disease) and AST/ALT less than 3 x ULN
* Absolute neutrophil count greater than 1500/mm3
* Platelet count greater than 100,000/mm3
* Women of childbearing age must have a negative blood pregnancy test
* Men and women of childbearing potential must be willing to use effective contraception while on treatment and for at least 3 months there after

Exclusion Criteria:

* Prior chemotherapy or radiation therapy for this lung cancer (history of prior lung cancer that has been treated and deeded inactive by the clinician is acceptable)
* Ineligible for cisplatin or carboplatin per medical oncologist
* Ineligible for pemetrexed per medical oncologist
* Greater than minimal, exudative, or malignant pleural effusion
* Calculated creatinine clearance by Cockcroft \& Gault method ≤45 ml/min
* Unstable congestive heart failure
* Ejection fraction \<50% as assessed by MUGA or echocardiogram
* Interstitial lung disease
* Patient requiring on-going treatment with a potent inhibitor (cyclosporin, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital with quinidine, ritonavir, valspodar, verapamil) or inducer of P-gp (St. John's wort or rifampin)
* Women who are breastfeeding