There are two different treatment modes for NSCLC patients who failed to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) after initially responding to EGFR-TKI. One is EGFR-TKI combined with chemotherapy and the other is chemotherapy followed by EGFR-TKI. It is unclear which one is more suitable to this group of lung cancer patients. So this phase Ⅱclinical trial is designed to compare the efficiency and safety of these two different treatment modes.

Responses to EGFR-TKIs are quiet dramatic and durable, especially in patients with EGFR gene classic mutations, such as 19 deletion or 21 leucine 858 arginine(L858R). However, most patients with NSCLC who respond to EGFR-TKIs eventually experience progression of disease after approximately 12 months. The lack of an established therapeutic option for NSCLC patients who have progressive disease after EGFR-TKIs failure poses a great challenge to physicians in terms of how best to manage this growing group of lung cancer patients.

In clinical practice some of the initially EGFR-TKI sensitive tumors which progressed evidence a striking increase in tumor volume within several weeks, after being taken off EGFR-TKI. This response is called "rebound phenomenon". Most experts still believe that these tumors continue to be "oncogene-addicted" to EGFR. So it is rational that EGFR-TKI combined with another chemotherapy regimen can be used to treat NSCLC after the failure of EGFR-TKI therapy.

However in some phase Ⅱclinical trials involved a few NSCLC patients who failed to EGFR-TKI therapy, another treatment mode, that is to say, at least one cytotoxic chemotherapy was used firstly then switched to EGFR-TKI therapy until progression of disease, was used and called reintroduction or retreatment of EGFR-TKI. Using this treatment mode, some investigators reported the partial remission (PR) and disease control rate (DCR) were observed in 21.7%-36% and 65.2%-86% NSCLC patients.

Inclusion Criteria:

• age ≥ 18 years
• histologically and cytologically proven non-small cell bronchogenic carcinoma (sputum cytology alone was not acceptable)
• clinical stages ⅢB or Ⅳ
• recurrent or refractory disease following previous first-line chemotherapy regimens containing platinum and second-line EGFR-TKIs therapy
• partial remission (PR) or stable disease (SD) at least for 6 months during previous EGFR-TKI treatment
• at least one bidimensionally measurable or radiographically assessable lesion
• Eastern cooperative oncology group performance status (ECOG PS) ≤ 2
• life expectancy ≥ 12 weeks
• adequate hematological, renal, and hepatic functions

Exclusion Criteria:

• additional malignancies
• uncontrolled systemic disease
• any evidence of clinically active interstitial lung disease
• newly diagnosed central nervous system (CNS) metastasis and not treated by radiotherapy or surgery
• pregnancy or breast feeding phase