Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

OBJECTIVES: Primary * To compare the overall survival (OS) of patients with advanced non-squamous non-small cell lung cancer (NSCLC) treated with maintenance therapy with bevacizumab vs pemetrexed disodium vs bevacizumab and pemetrexed disodium following induction therapy. Secondary * To determine the response rate in patients treated with these regimens. * To evaluate the progression-free survival (PFS) of patients treated with these regimens. * To define the toxicity of these regimens in these patients. * To determine the frequency of polymorphisms in VEGF 3578 AA, 1154 AA, ABCB1 G2677TT/AA, and ERCC-118 TT in patients treated with induction therapy comprising paclitaxel, carboplatin and bevacizumab and determine the association between genotypes and response rate. * To determine the association between bevacizumab and pemetrexed disodium population pharmacokinetics and patient-specific covariate with bevacizumab or pemetrexed disodium toxicity. * To determine the frequency of TSER\*3 polymorphisms in NSCLC and the association between TSER polymorphisms and benefit from pemetrexed disodium. * To evaluate TS and ERCC1 expression by RT-PCR and MTAP mutations in existing tumor specimens as a predictor of pemetrexed disodium response. * To evaluate polymorphisms within CYPs 2C8, 3A4, 3A5 and/or the UGT1A1 collectively or monogenically as markers for variation in efficacious and/or toxic response of individuals to treatment with taxanes. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to gender (male vs female), stage of disease (IIIB-T4Nx \[with nodule in ipsilateral lung lobe and not candidate for combined chemotherapy and radiation\] and IV M1a vs IV M1b vs recurrent), best response to first-time therapy (complete response/partial response vs stable disease), and smoking status (never vs smoker). * Induction therapy (Arm I): Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. * Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Treatment begins within 6 weeks of the last day of induction chemotherapy administration. * Arm A: Patients receive bevacizumab IV over 30-90 minutes on day 1. * Arm B: Patients receive pemetrexed disodium IV over 10 minutes on day 1. * Arm C: Patients receive bevacizumab as in arm A and pemetrexed as in arm B. In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Some patients undergo blood sample collection at baseline and periodically during study for correlative studies. After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 2-5 years.