After first-line chemotherapy for non-small cell lung cancer, waiting for recurrence or progression, about 50% of patients lose the opportunity of second-line treatment due to rapid disease progression, thus scholars also ask whether giving maintenance therapy after completing first-line chemotherapy can prolong the time of recurrence or disease progression and thus prolong survival? Therefore, maintenance therapy for lung cancer has become a hot topic in the past two years. Maintenance therapy includes two modes, namely, maintenance with the same drug and maintenance with a different drug. Co-drug maintenance refers to the continuation of treatment with one of the drugs after 4-6 cycles of first-line treatment if the disease has not progressed. Currently, the U.S. FDA approved bevacizumab for maintenance treatment of nonsquamous cancer based on the ECOG 4599 study, but the study was designed with a control group that did not use bevacizumab, so it is unclear whether maintenance therapy is truly beneficial. Maintenance with a different drug is the equivalent of early second-line therapy if it does not progress after 4 to 6 cycles of first-line therapy and is continued with another drug. The US FDA approved pemetrexed and erlotinib for maintenance therapy after effective first-line chemotherapy or SD for non-squamous NSCLC based on the JMEN study and the SATURN study, respectively. In terms of the origin of maintenance therapy, “continued maintenance” may be more in line with the intent of maintenance therapy, but it also has disadvantages. This is because after 4-6 cycles of first-line chemotherapy, most of the residual tumor cells are already selected “drug-resistant clones”, and maintenance therapy with drugs from the first-line regimen may have little effect at this time. There are no clinical studies comparing head-to-head continuation versus switch maintenance, but some useful information can be obtained from the JMEN study, which examined pemetrexed switch maintenance, and the PARAMOUNT study, which examined continuation maintenance. The risk of disease progression was reduced by 36%. In the JMEN study, the non-squamous subgroup had a PFS of 4.4 months from maintenance treatment, which was 2.6 months longer than the control group, and the risk of disease progression was reduced by 56%. To some extent, this suggests that switching to maintenance therapy may be preferable to continued maintenance. However, the most criticized aspect of maintenance therapy is – is it only an early second-line treatment? Is it similar in efficacy to second-line therapy? Are there additional financial costs and adverse effects? Therefore, selective maintenance is the most important concept when deciding whether maintenance therapy is needed. The question of how to interpret “appropriate” in this context leads to the next question – the clinical factors that influence maintenance therapy. The potential benefits of maintenance therapy are mainly symptom reduction and prolonged survival; the negative effects include excessive financial costs and additional side effects. What about other clinical factors? If patients have good physical status (PS) and symptoms caused by lung cancer are not controlled, they are more likely to benefit from maintenance therapy; while for those with poor PS scores, additional side effects may reduce their quality of life and even affect survival. Therefore, it is crucial to select the right patient at the right time: PS score Brodowicz et al. reported a phase III controlled clinical study of gemcitabine in maintenance therapy versus best supportive care (control group) after first-line treatment for advanced NSCLC, which showed that gemcitabine monotherapy maintenance therapy prolonged TTP. further stratified analysis found that patients with good general status (KPS ’80), survival was significantly prolonged after maintenance therapy. The 2010 phase III trial of gemcitabine + carboplatin after gemcitabine maintenance versus best supportive care; and the 2010 three-arm study IFCT-GFPC 0502 of gemcitabine + cisplatin after gemcitabine maintenance versus erlotinib maintenance versus observation. of these, only the 2nd study had a negative PFS result, which may be related to the high proportion of those with poorer PS scores (56 percent and 58 percent, respectively). However, the impact of PS on maintenance therapy may be mainly on cytotoxic drugs, which have little impact on maintenance therapy with less adverse effects of targeted drugs. First-line chemotherapy efficacy The JMEN and SATURN studies all showed a greater benefit of maintenance therapy in those with stable disease (SD) after first-line chemotherapy. In contrast, in the IFCT-GFPC 0502 study, it was the first-line treatment remission group that had the greater benefit in the continued maintenance treatment group. This may again reflect the difference between switching and continuing maintenance therapy: the former gives SD patients with less than optimal first-line outcomes the opportunity to further improve their outcomes due to maintenance with drugs other than first-line therapy, while the latter perpetuates the outcomes of first-line remission patients. Clinical characteristics and molecular targets The JMEN study has demonstrated that the non-squamous subgroup has much better outcomes than the squamous subgroup: PFS periods of 4.4 and 1.8 months, and OS periods of 15.5 and 10.3 months, respectively. 2012 ASCO Congress announced the final results of the randomized double-blind controlled phase III study PARAMOUT. patients who received 4 cycles of pemetrexed + cisplatin chemotherapy and were randomized to pemetrexed or placebo + best supportive care (BSC) maintenance therapy until disease progression if they did not progress and had PS 0 or 1. Preliminary results suggested that pemetrexed maintenance therapy significantly reduced the risk of disease progression in patients compared to placebo (HR=0.62, p<0.0001). The final results presented at this congress suggest that pemetrexed maintenance therapy significantly reduced the risk of death by 22% (HR=0.78). Patients in complete remission (CR) or partial remission (PR) after induction chemotherapy (45%) showed the same improvement in survival compared to those with stable disease (SD). Thus, for advanced non-squamous NSCLC, pemetrexed maintenance therapy offers a survival advantage over placebo. This study clearly shows that the continuation of pemetrexed maintenance therapy after pemetrexed combined with cisplatin induction chemotherapy may further benefit patients compared to induction chemotherapy alone. This is sufficient to change the treatment paradigm for non-squamous NSCLC. There may also be a superior population for TKI maintenance therapy: the median PFS period in the SATURN study was 12.3 months and the median OS period was 12.0 months, compared to a median PFS period of 4.8 months and a median OS period of 18.7 months in the INFORM study conducted in Asia. Although there was no head-to-head comparison, this may suggest that the benefit of TKI maintenance therapy would be more pronounced in Asian populations, the essence of which is feared to be the EGFR gene mutation. In the SATURN study, the risk ratios for disease progression were 0.1 and 0.78 for EGFR mutant and wild-type patients versus controls, respectively. In the INFORM study, the PFS duration was 16.6 months versus 2.8 months for the EGFR mutant and control groups, respectively, compared to 2.7 months versus 1.5 months for wild-type. Although the small sample size of mutants (22 in SATURN and 15 in INFORM) makes the results of both studies less convincing, the selection of those suitable for maintenance therapy based on molecular targets such as EGFR mutations will be the final result. The differences between the Eastern and Western races make the path opened by the European and American studies may not be suitable for the national population, and we look forward to more. Finally, whether or not to choose maintenance therapy must respect the patient's wishes. In conclusion, selective maintenance is an important concept of maintenance therapy for advanced NSCLC.