Comparison of Cost-effectiveness of Continuation Maintenance Therapy With Six Cycles of Pemetrexed Versus Pemetrexed Until Disease Progression for Metastatic Non-squamous Non-small-cell Lung Cancer

Inclusion Criteria:

1. Males and females ≥ 20 years of age
2. ECOG performance status of 0-1
3. Histologically or cytologically verified non-squamous NSCLC
4. Stage IV disease, as defined by American Joint Committee on Cancer 7th edition staging, prior to first-line or second-line chemotherapy with pemetrexed plus platinum
5. At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
6. Completion of 4 cycles of first-line or second-line chemotherapy with pemetrexed plus platinum and documented radiographic evidence of a complete or partial tumor response or stable disease by RECIST 1.1
7. Adequate organ function, including followings:

   Bone marrow:

   Absolute neutrophil count ≥ 1.5 x 103 /μL White blood cell ≥ 3.0 x 103 /μL Platelet count ≥ 75 x 103 /μL Hemoglobin ≥ 8.0 g/dL

   Hepatic:

   Total bilirubin ≤ 1.5 x upper normal limit (UNL) Aspartate aminotransferase (AST) ≤ 3.0 x UNL (≤ 5.0 x UNL if liver metastasis) Alanine aminotransferase (ALT) ≤ 3.0 x UNL (≤ 5.0 x UNL if liver metastasis)

   Renal:

   Estimated glomerular filtration rate ≥ 30 mL/min
8. Estimated life expectancy of at least 6 months
9. Ability to comply with study and follow-up procedures
10. Signed informed consent document

Exclusion Criteria:

1. Squamous cell and/or mixed small-cell, non-small-cell histology
2. Prior participation in any investigational drug study within 4 weeks
3. Prior malignancy other than NSCLC, except those remain disease-free for ≥ 3 years after curative treatment, non-melanoma skin cancer or in situ cervical cancer
4. Serious concomitant systemic disorders, such as acute or recent myocardial infarction (\< 6 months before enrollment), congestive heart failure with New York Heart Association functional class II\~IV, frequent exacerbations of chronic obstructive pulmonary disease (≥ 2 hospitalizations per year), or recent cerebrovascular disease (\< 6 months before enrollment)
5. Active uncontrolled infections or HIV infection
6. Current or planned pregnancy, or breast feeding in women
7. Symptomatic central nervous system metastasis unless the patient has completed successful local therapy and has been off corticosteroids for ≥ 4 weeks
8. Concurrent administration of any other antitumor therapy including chemotherapy, target therapy, immunotherapy, and hormone therapy
9. Psychiatric disorders that would compromise the patient's compliance or decision