It has not been established whether platinum-based doublets is better than single agent chemotherapy in EGFR mutant NSCLC patients who failed first-line EGFR TKI.

In this prospective trial, the investigators try to evaluate whether the progression-free survival of pemetrexed/cisplatin (PC) regimen is longer than that of pemetrexed single(P) regimen in NSCLC patients who have progressed after first line treatment of EGFR-TKI.

Inclusion Criteria:

• Histologically confirmed nonsquamous NSCLC with activating EGFR mutation (on exon 19 deletion or exon 21 L858R mutation)
• Stage IIIb, IV or recurrent NSCLC (AJCC 7th criteria)
• Age ≥ 20 years
• ECOG performance status of 0 or 1
• At least one measurable lesion by RECIST 1.1
• Progression after first line treatment with EGFR TKIs for advanced NSCLC
• Asymptomatic brain metastasis or symptomatic brain metastasis treated with local treatment such as operation, whole brain radiotherapy, or gamma-knife surgery
• At least 2 weeks later after whole brain radiotherapy or palliative radiotherapy
• Adequate renal function: estimated creatinine clearance ≥ 45 mL/min
• Organ function as evidenced by the following; Absolute neutrophil count > 1.5 x 109/L; platelets > 100 x 109/L; total bilirubin ≤1.5 UNL; AST and/or ALT < 3 UNL, in case of known hepatic metastasis, AST/ALT< 5 UNL
• Written informed consent form
• No other previous systemic chemotherapy

Exclusion Criteria:

• Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia
• Patients with post-obstructive pneumonia or uncontrolled serious infection
• Pregnant or nursing women (Women of reproductive potential have to agree to use an effective contraceptive method)
• Uncontrolled symptomatic brain metastasis
• Presence of third space fluid which cannot be controlled by drainage
• Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, well-treated thyroid cancer.