Pemetrexed vs Pemetrexed Plus Cisplatin in EGFR-mutant NSCLC Patients After First Line EGFR-TKIs Failure

Inclusion Criteria: 1. Informed consent must be signed. 2. Age of ≥18 and \< 75 years old. 3. Performance status (PS) 0 - 2 on the Eastern Cooperative Oncology Group (ECOG) Scale. 4. Histologically confirmed stage IIIB/IV advanced NSCLC harboring activating EGFR mutation. 5. Chemotherapy-naïve for advanced disease. 6. Acquired resistance is measured according to the Jackman criteria. Achieved complete remission (CR)/partial remission (PR)≥4 months or stable disease (SD)\>6 months with first-line EGFR TKIs (Gefitinib or Erlotinib or Icotinib) for advanced NSCLC. 7. Disease progression(RECIST) \<4 weeks prior to study randomization. 8. Adequate organ function including the following: * Bone marrow: absolute neutrophil count (ANC) ≥1.5 x 109/L, platelets ≥100 x 109/L hemoglobin ≥9 g/dL. * Hepatic: total bilirubin ≤1.5 times the upper limit of normal (ULN), liver transaminases: aspartate transaminase (AST or SGOT) and alanine transaminase (ALT or SGPT) ≤2.5 times ULN. AST and ALT ≤ 5 x ULN may be included only if Patient has liver metastasis. * Renal: calculated creatinine clearance ≥45 mL/min (using the standard Cockcroft-Gault formula). 9. Patients have resolution to \<Grade 2 by the CTCAE (Version 4.0), of all clinically significant toxic effects of prior anti-cancer therapy (with the exception of rash and alopecia). 10. Patients with stable central nervous system (CNS) metastasis successfully treated with local therapy, or with asymptomatic CNS metastasis are eligible. Treated stable CNS metastases are allowed; the patient must be stable after radiotherapy for ≥2 weeks and off of corticosteroids for ≥1 week. 11. At least one measurable lesion as defined by RECIST 1.1 criteria. 12. Previous palliative radiation therapy is allowed, but limited in \<25% of the bone marrow and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed one month before study entry. Radiotherapy should not be administered to target lesions selected for this study, unless progression of the selected target lesions within the radiation portal is documented. 13. Estimated life expectancy of at least 8 weeks. 14. For women: must be surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method during and for 3 months after the treatment period; must not be pregnant and must not be lactating; negative pregnancy test is required for women of childbearing potential. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential. For men: must be surgically sterile or compliant with a highly effective contraceptive method during and for 3 months after the treatment period. 15. Patient compliance and geographic proximity that allow adequate follow-up. Willingness to provide blood samples for EGFR mutation test at baseline and disease progression. Exclusion Criteria: 1. Patient got disease relapsed within 12 months after post-operative adjuvant chemotherapy, thereafter got failure from subsequent EGFR-TKI treatment cannot be enrolled. 2. History of another malignancy within the last 5 years except cured carcinoma in-situ of uterine cervix, cured basal cell carcinoma of skin and superficial bladder tumors \[Ta, Tis \& T1\]. 3. Any unstable systemic disease (including active infection, hepatic, renal or metabolic disease) or serious concomitant disorders that will compromise the safety of the patient, or compromise the patient's ability to complete the study, at the discretion of the investigator. 4. Significant cardiovascular event: congestive heart failure \>New York Heart Association (NYHA) class 2; unstable angina, active coronary artery disease (myocardial infarction more than 1 year prior to study entry is allowed); serious cardiac arrhythmia requiring anti-arrythmic therapy ( beta blockers or digoxin are permitted) or uncontrolled hypertension. 5. History of significant neurological or mental disorder, including seizures or dementia. 6. Incision from operation has not healed before the start of study treatment (Small incision for biopsy is eligible.) 7. Presence of clinically uncontrollable third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry. 8. Inability or unwillingness to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) from 2 days before to 2 days after administration of pemetrexed. If a patient is taking an NSAID (including Cox-2 inhibitors) or salicylate with a long half-life (e.g. naproxen, piroxicam, diflusinal, nabumetone, rofecoxib, or celecoxib), it should not be taken from 5 days before to 2 days after the administration of pemetrexed. 9. Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone. 10. Inability to comply with protocol or study procedures. 11. Concurrent use of any other anti-tumor therapy during study.