In the last decade, the place of chemotherapy in progressive non-small cell lung cancer has been established no more than 6 courses of platinum-based two-drug regimen chemotherapy is currently the first-line standard of care for patients in good physical status. Although third-generation cytotoxic agents combined with platinum have further improved survival in progressive NSCLC, the prognosis remains poor, with first-line chemotherapy rates ranging from 20-40% and median survival of approximately 8 months, and the existing regimens have reached a “chemotherapy efficacy plateau”. In addition to the expansion of new drugs to improve outcomes for patients with NSCLC, maintenance therapy offers a new clinical idea to improve the potential efficacy of existing drugs. Several years ago, the role of maintenance therapy has been under debate due to the limited number of reported maintenance therapy studies, the heterogeneity of individual studies, and different interpretations of the findings; recently, with the intervention of some well-tolerated chemotherapeutic agents and molecularly targeted drugs, the status of maintenance therapy has been gradually improved. I. The theoretical basis of maintenance therapy Maintenance therapy is to receive drugs after patients have received a certain course of chemotherapy to achieve maximum tumor control effect, in order to achieve maximum tumor remission and survival, in the absence of serious toxic reactions, maintenance therapy will continue until a certain time or until disease progression occurs. The maintenance drug may be the same drug used in induction therapy or another relatively low-toxicity, non-cross-resistant drug. In published clinical studies on maintenance therapy, the population composition varies, as in some studies, only patients who have achieved complete or partial remission may enter maintenance therapy; in others, patients who are stable after induction therapy may also be enrolled. The rationale for maintenance therapy stems from the Goldie and Coldman hypothesis, which suggests that early use of non-cross-resistant drugs can kill more tumor cells before resistance develops. The most effective drugs should be used for consolidation therapy to achieve maximum therapeutic benefit. In addition, the induction phase is thought to be a possible in vivo drug sensitivity analysis, and these patients are most likely to benefit from maintenance therapy. II. Maintenance therapy with chemotherapeutic agents Few early clinical studies have been able to fully assess the value of maintenance therapy for progressive non-small cell lung cancer. These randomized studies evaluating the outcomes of patients with progressive NSCLC receiving induction chemotherapy with platinum-containing regimens followed by maintenance chemotherapy with third-generation agents (e.g., nolvadex and paclitaxel) unfortunately compromised the statistical significance of the results due to either design flaws or the fact that only a small proportion of patients entered maintenance therapy. The induction regimen was 2 cycles of MIC (mitomycin, isocyclophosphamide, and cisplatin) followed by radiotherapy in some stage IIIB patients, and 4 cycles of MIC chemotherapy in stage IIIB and IV patients. 227 patients were effectively treated with induction therapy, 181 of whom were randomized 1:1 to the Noviben maintenance Although 14% of patients responded to maintenance therapy, the 1 and 2 year survival rates were 42.2%, 20.1% and 50.6%, 20.2% in the maintenance and observation groups, respectively, with no statistically significant difference between the two groups, nor was there a significant difference in progression-free survival between the two groups; this disappointing result is consistent with the reported poorer outcome of novibrium after failure of platinum-containing regimen chemotherapy. This disappointing result is consistent with the poorer outcomes reported for second-line therapy after failure of platinum-containing regimens, the main reason for which may be drug-induced adverse effects that are not tolerated by patients receiving maintenance therapy. Whether the choice of a newer induction chemotherapy regimen (e.g., replacing the MIC regimen with a platinum-containing three-generation two-drug regimen) and maintenance drugs can improve outcomes. In a phase II multicenter randomized study, Belani et al. To evaluate the optimal regimen of weekly paclitaxel in combination with carboplatin for the treatment of progressive NSCLC, patients were randomized into 3 different weekly paclitaxel in combination with carboplatin regimens, and after 4 cycles of chemotherapy, patients who were effective or stable on treatment were randomized to receive weekly paclitaxel maintenance or observation alone, with a total of 401 patients enrolled, of whom 130 patients were enrolled in the maintenance treatment group. Data from this treatment group were integrated with results from another phase III study comparing weekly and 3-week paclitaxel combined with carboplatin followed by weekly paclitaxel maintenance, with a total of 206 patients receiving paclitaxel maintenance, and overall a median survival of 75 weeks in the maintenance group compared with a median survival of 58 weeks without maintenance, and in both clinical studies, weekly paclitaxel maintenance therapy was better tolerated; although there was a significant prolongation of median survival time in patients receiving maintenance therapy, since the purpose of these studies was to determine the optimal regimen of carboplatin combined with paclitaxel chemotherapy, not to determine the effectiveness of maintenance therapy, it is still not possible to draw definitive conclusions regarding maintenance therapy, but it is suggested that the selection of less toxic single agents as maintenance therapy is feasible for progressive non-small cell lung cancer. A study by Fidias et al. demonstrated the potential role of docetaxel maintenance therapy in patients with progressive non-small cell lung cancer who received 4 cycles of carboplatin in combination with gemcitabine as induction chemotherapy, and who responded to treatment or were stable were randomized to 2 groups, with one group of patients receiving immediate docetaxel maintenance therapy (immediate group) and one group of patients receiving maintenance therapy (immediate group). One group of patients received docetaxel as maintenance therapy immediately (immediate group) and the other group received docetaxel as salvage therapy at the time of disease progression (delayed group). 231 of the 526 patients enrolled were randomized to the clinical study after initial treatment, and the results showed that the overall efficiency of the immediate group was higher than that of the delayed group. Median survival, 6.5 months in the immediate group was significantly higher than 2.8 months in the delayed group, and there was no significant difference in quality of life assessment between the two groups. The preliminary results suggest that immediate docetaxel maintenance therapy significantly prolonged the PFS of patients and had a tendency to improve overall survival, which provides another strong evidence for maintenance therapy in progressive non-small cell lung cancer. The good tolerability of gemcitabine makes it an ideal option for evaluating maintenance therapy. Brodowicz et al. evaluated the role of gemcitabine maintenance therapy in a phase III clinical study in which patients with progressive NSCLC received 4 cycles of cisplatin in combination with gemcitabine chemotherapy. Of a total of 352 patients enrolled, a total of 206 patients received gemcitabine monotherapy and best supportive care in a 2:1 ratio, and the results showed that gemcitabine maintenance therapy significantly improved the time to disease progression, with 6.6 months in the maintenance group compared with 5 months in the best supportive care group; there was a trend toward longer overall survival in the maintenance group, but the difference between the two groups was not statistically significant. The difference was not statistically significant; maintenance therapy facilitated patient symptom control. The study confirmed the feasibility and evidence of clinical benefit of gemcitabine as maintenance therapy, which was a turning point in maintenance therapy research. Belani et al. reported the efficacy of pemetrexed in maintenance therapy after standard treatment, which was the first study to demonstrate that pemetrexed significantly improved overall survival as maintenance therapy. In this randomized, double-blind, phase III clinical trial, patients received either pemetrexed (441 patients) or placebo (222 patients) in combination with best supportive care regimens. All patients were advanced non-small cell lung cancer patients (both squamous and non-squamous subtypes) who were progression-free after receiving 4 cycles of platinum-containing regimen chemotherapy. Overall survival was 13.4 months in the pemetrexed-treated group compared with 10.6 months in the placebo group. In the non-squamous subgroup (481 patients), overall survival was 15.5 months for patients treated with pemetrexed compared with 10.3 months for those in the placebo group. Patients with squamous carcinoma did not appear to benefit from treatment with pemetrexed, a result that has been confirmed in previous studies. The incidence of serious adverse reactions was low, but more frequent in the pemetrexed group, especially malaise and reduced white blood cells. In those patients treated with pemetrexed for a longer period of time, there was no increased incidence of adverse reactions and no drug-related deaths were reported. dr Belani concluded, “Non-squamous tissue type predicts improved efficacy of pemetrexed in advanced non-small cell lung cancer, and the improvement in 5-month survival time is significant for overall survival. “