The current concept of maintenance therapy is divided into two types: continuation of maintenance therapy and maintenance therapy with drug changes. Continued maintenance therapy refers to treatment with at least one drug that was used in the first-line regimen after 4-6 cycles of first-line therapy if no disease progression has occurred. Maintenance therapy with a different drug not included in the first-line regimen is initiated after 4-6 cycles of first-line therapy if no disease progression occurs. The ideal maintenance drug should be effective as a single agent, have low side effects, and be easy to use. Chemotherapeutic agents for maintenance therapy A randomized, double-blind, multicenter phase III clinical study (JMEN) evaluating pemetrexed maintenance therapy was presented by Ciuleanu et al. at the ASCO Annual Meeting in 2008. The median survival (OS) was better in the pemetrexed maintenance group than in the placebo group (13.4 months versus 10.6 months), with a 21% reduction in the risk of death, with a more pronounced survival benefit in patients with non-squamous cancer (15.5 months versus 10.3 months) and a 30% reduction in the risk of death. Because of the scientific design of this study and the prolonged survival achieved, maintenance therapy has finally seen the light of day with the approval of pemetrexed in the US and EU for the maintenance treatment of non-squamous cancer patients with progression-free disease after platinum-based therapy, and is recommended in the NCCN guidelines. Targeted therapy for maintenance treatment Targeted drugs have attracted more attention in the research of maintenance treatment because of the advantages of small side effects and convenience of administration. In 2009, Italian scholars Cappuzzo et al) reported the preliminary results of the multicenter phase III study (SATURN) of maintenance therapy with erlotinib at the ASCO annual meeting, and the trial results were subsequently supplemented at the World Conference on Lung Cancer and the European Society of Medical Oncology (ESMO) congress that year. The results showed that PFS was significantly prolonged in the erlotinib group compared to the placebo group (12.3 weeks versus 11.0 weeks); it was also prolonged in the OS maintenance group, 12.0 months versus 11.0 months, especially in the maintenance group of patients with non-squamous cancer, with 13.7 months in the maintenance group (272 patients) and 10.5 months in the placebo group (257 patients). Subgroup analysis showed that patients of different gender, pathological type, ethnicity, smoking status, and EGFR wild type or mutation could benefit from erlotinib maintenance therapy. In addition maintenance therapy delayed the onset of pain and the use of analgesics in patients. The safety profile of erlotinib maintenance therapy is good, and the positive results of the SATURN study have provided further insight into maintenance therapy. In light of the SATURN study, the 2010 NCCN guidelines recommended that patients with advanced NSCLC who have not progressed after first-line chemotherapy can be treated with maintenance therapy with erlotinib replacement. A phase III clinical study of gefitinib maintenance therapy (INFORM) was also reported by our scholar Tension at this year’s ASCO annual meeting. This study involved 27 oncology centers in China and showed that PFS was significantly longer in the gefitinib group than in the control group (4.8 months vs. 2.6 months), with a 58% reduction in the risk of disease progression in the maintenance group and an unpublished OS. Patients were well tolerated. EGFR testing was performed in 79 of the enrolled patients, with a mutation rate of 38%; among patients with mutations, PFS was 16.6 months and 2.7 months in the gefitinib and control groups, respectively, with a risk ratio of 0.16, so patients with EGFR mutations had a greater benefit, but further validation is needed because of the small sample size. Clinical options for maintenance therapy Current guidelines for the treatment of advanced non-small cell lung cancer recommend either observation or maintenance therapy after 4-6 cycles of first-line therapy. If first-line therapy is completed and the decision to choose maintenance therapy is made, in addition to the main factors of the patient’s general condition, the patient’s wishes and economic conditions, the choice of specific drugs should be reasonably selected and weighed according to the patient’s specific situation. Chemotherapy drug selection: The 2011 NCCN guidelines recommend (Class 2B) pemetrexed maintenance therapy for continued maintenance therapy and maintenance therapy with drug replacement for patients with non-squamous cancer. Clinical trials have shown that pemetrexed maintenance therapy can extend survival by 2.8 months compared to placebo, especially for patients with non-squamous cancer by 5.2 months, so when choosing chemotherapy drugs for maintenance, pemetrexed should be preferred for patients with non-squamous cancer. Choice of targeted agents The 2011 NCCN guidelines recommend (Class 2B) that erlotinib can be switched to maintenance therapy after 4-6 cycles of first-line chemotherapy with a platinum-containing two-drug regimen. Clinical trials have shown that erlotinib maintenance therapy prolongs survival by 1 month compared to placebo (12.0 months versus 11.0 months). Compared to intravenous targeted drugs, erlotinib has the advantages of oral convenience, low side effects, and no need for hospitalization, so the clinical decision to use erlotinib maintenance depends on the patient’s specific situation. Because of the modest survival extension benefits of erlotinib, the UK’s National Institute for Health and Clinical Excellence (NICE) issued a guideline in June this year saying that it was uncertain whether erlotinib would provide sufficient benefit to patients given its high cost, and therefore it was not recommended for maintenance treatment. We look forward to more clinical trials to verify the benefits of erlotinib maintenance therapy. Both bevacizumab and cetuximab are recommended as NCCN for continued maintenance therapy. Because it is not maintenance by drug exchange, the first line has to be combined with chemotherapy for 4-6 cycles, very expensive, inconvenient to administer and non-hematologic toxicity that cannot be ignored, although it is a class 1 recommendation, only very few people may be able to choose it in our current national situation. In terms of patient selection bevacizumab is used for non-squamous cancers and cetuximab is indicated for patients with high EGFR expression. Three clinical trials showed that gefitinib maintenance therapy prolonged disease-progression-free survival by 1.2-2.2 months compared to the observation or placebo groups, one study found prolonged survival in patients with adenocarcinoma, and another study analysis reported in our tension found a very significant prolongation of disease-progression-free survival in patients with EGFR mutations (16.6 months versus 2.7 months). Although there was no survival benefit from the trial, gefitinib maintenance therapy could be an option for special populations, such as those with a high prevalence of EGFR mutations, such as adenocarcinoma, women and non-smokers, since gefitinib has the same benefits as erlotinib and is relatively less costly.