Continued maintenance or maintenance with a new drug From the origin of maintenance therapy, “continued maintenance” may be more in line with the intention of maintenance therapy, but it also has disadvantages. This is because after 4-6 cycles of first-line chemotherapy, most of the remaining 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. Therefore, in the eyes of many scholars, maintenance therapy should specifically refer to “maintenance therapy with drug replacement”. Various analyses have suggested that maintenance with drug replacement may be preferable to continuation. Clinical studies comparing head-to-head maintenance versus switch maintenance do not yet exist, but some useful information can be obtained from the JMEN study, which examined switch maintenance with pemetrexed, and the PARAMOUNT study, which examined switch maintenance with continued maintenance. So far, the phase III clinical studies of maintenance treatment that obtained prolonged overall survival include only the JMEN and SATURN studies. This may also be a reflection of the advantages of switching maintenance therapy. 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? Does it increase the financial cost and adverse effects in vain? In a phase III trial, those who did not progress after the end of first-line gemcitabine + carboplatin chemotherapy were randomized to immediate docetaxel treatment or docetaxel second-line treatment after progression. The results showed that the former had a significantly longer PFS period and a trend toward a longer OS period. This benefit disappeared when further analysis was performed only in those who actually received docetaxel. This suggests that if patients are followed closely enough to ensure that they receive second-line therapy at the time of disease progression, then switching to maintenance therapy is actually equivalent to second-line therapy. But in fact this is very difficult to do. As can be seen, the advantage of maintenance therapy is precisely that it prevents patients from losing access to second-line therapy. Therefore, it is reasonable to offer maintenance therapy to the right patients, and switching to maintenance may be preferable to continuing maintenance therapy. The question of how to interpret the word “appropriate” here leads to the next question. The potential benefits of maintenance therapy are primarily symptom relief and prolonged survival; the negative effects include excessive financial costs and additional side effects. Thus, if economic factors are excluded, patients with good physical status and uncontrolled symptoms caused by lung cancer 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. PS score Three gemcitabine maintenance studies suggest the possible impact of PS: the phase III trial of gemcitabine maintenance versus best supportive care after gemcitabine + cisplatin reported by Thomas et al. in 2006; the phase III trial of gemcitabine maintenance versus best supportive care after gemcitabine + carboplatin in 2010; and the 2010 gemcitabine maintenance versus erlotinib maintenance versus observation Of these, only the second study had a negative PFS result, which may be related to its high proportion of poor PS scores (56% and 58% in the two groups, 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 after first-line chemotherapy. In contrast, in the IFCT-GFPC0502 study, it was the first-line treatment remission group that benefited more from continued maintenance therapy. This may again reflect the difference between switching and continuing maintenance therapy: the former gives SD patients with less-than-optimal first-line efficacy the opportunity to further improve their efficacy due to maintenance with drugs other than first-line therapy, while the latter perpetuates the efficacy of first-line remission patients. However, is there also a drug difference in the link between first-line chemotherapy efficacy and maintenance therapy? This requires further confirmation. Clinical characteristics and molecular targets The JMEN study has confirmed that the non-squamous subgroup has a much better efficacy than the squamous subgroup: PFS periods of 4.4 and 1.8 months and OS periods of 15.5 and 10.3 months, respectively. 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, while the median PFS period reached 4.8 months and the median OS period reached 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, wild-type patients and controls, respectively. In the INFORM study, the PFS period was 16.6 months versus 2.8 months for the EGFR mutant, control group, respectively, compared to 2.7 months versus 1.5 months for wild-type. Although the sample size of those with mutations was too small to make the results of both studies convincing, selecting those suitable for maintenance therapy based on molecular targets such as EGFR mutations will be the final result.