Study of Pemetrexed Plus Cisplatin as First-line Therapy in Patients With Advanced Non-squamous NSCLC

Inclusion Criteria: * Histologic or cytologic diagnosis of non-squamous NSCLC, that is not amenable to curative treatment with surgery or radiation therapy. This population encompasses advanced stage patients with select stage IIIB (with pleural or pericardial effusion) or stage IV disease. Histologic or cytologic documentation of recurrence is required in patients who were previously completely resected and now have progressive disease. * Tissue must be available to generate and apply the genomics predictor. If not obtained at the time of diagnosis, then subject must consent to another biopsy. If patient had prior radiation therapy, tissue biopsy for genomics analysis must be outside radiation field. * At least one, non-radiated, measurable lesion by RECIST criteria. * ECOG performance status of 0 or 1 * No prior chemotherapy, biologic or targeted therapy for any malignancy. * Prior radiation therapy is permitted if ≥1 week since completion of radiation treatment. Radiation must be \<25% of bone marrow reserve. * Age greater than 18 years. * No previous or concomitant malignancy in the past 5 years other than surgical management for carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin. * No other serious medical or psychiatric illness. * Signed informed consent. * Females of child-bearing potential (not surgically sterilized and between menarche and 1 year post menopause) must test negative for pregnancy within 7 days prior to or at the time of enrollment based on a serum pregnancy test. Both sexually active males and females of reproductive potential must agree to use a reliable method of birth control, as determined by the patient and their health care team, during the study and for 3 months following the last dose of study drug. * Required laboratory data within two weeks of enrollment: 1. ANC or AGC greater than 1500 per uL 2. Platelets greater than 100,000 per uL 3. Total bilirubin less than 1.5mg/dL 4. Creatinine clearance greater than or equal to 45 ml/min. 5. SGOT/SGPT less than or equal to 3x/ULN except in presence of known hepatic metastases in which it may be up to 5x ULN. Exclusion Criteria: * Patients with squamous cell NSCLC. * Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. * Concurrent administration of any other anti-tumor therapy. * Inability to comply with protocol or study procedures. * Active infection requiring IV antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy. * Documented symptomatic or untreated central nervous system (CNS) metastases (except if adequately treated and stable for at least 2 weeks). * Major surgery within 2 weeks of study or other serious concomitant systemic disorders that, in the opinion or the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study. * Myocardial infarction having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia or cardiac failure not controlled by medications. * Have peripheral neuropathy of CTCAE Grade 1 or higher * Contraindications to corticosteroids. * Inability or unwillingness to take folic acid or vitamin B12 supplementation. * Unwillingness to stop taking herbal supplements while on study. * Presence of clinically significant third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study entry and throughout study enrollment as the distribution of pemetrexed in this fluid space is not fully understood. * Recent (within 30 days before enrollment) or concurrent yellow fever vaccination. * Have prior known allergic/hypersensitivity reaction to any of the components of study treatment * Inability to discontinue administration of aspirin at a dose greater than 1300 mg/day or other non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days for long-acting agents such as piroxicam). * Female patients that is pregnant or breast-feeding.