Lung cancer is the malignant tumor with the highest incidence worldwide, surgery, radiation therapy and chemotherapy (targeted therapy) are still the three major treatment methods for lung cancer. Some new targeted therapeutic agents have gradually entered the clinic, changing the treatment paradigm of advanced NSCLC, especially in the second and third line treatment. However, chemotherapy is still the cornerstone of advanced NSCLC treatment. New advances in chemotherapy for advanced NSCLC in recent years are briefly summarized as follows. 1, first-line chemotherapy efficacy reached the platform Platinum-containing two-drug regimen is the standard first-line regimen for advanced NSCLC; two-drug regimen is significantly better than single-drug regimen in both remission rate and survival; three-drug regimen significantly improves objective remission rate, but overall survival is similar to two-drug regimen, with no significant difference and increased toxicity; non-platinum regimen can be used as an alternative for patients who cannot tolerate platinum-based regimen. Results of a randomized phase I clinical trial of cisplatin + pemetrexed vs. cisplatin + gemcitabine for locally advanced or metastatic NSCLC showed that; median overall survival and progression-free survival time were not significantly different between the two groups, with less toxicities in the pemetrexed group. However, in patients with squamous lung cancer, the three-drug regimen had a TTP of 7.0 months and an OS of 13.5 months, both of which were significantly better than the two-drug regimen, suggesting that squamous cancer may benefit from better survival with the three-drug regimen. ansari et al. compared the efficacy of gemcitabine combined with carboplatin, gemcitabine combined with paclitaxel and paclitaxel combined with carboplatin in the first-line treatment of advanced NSCLC and found similar efficacy between the 3 regimens and found that survival was similar between patients aged <70 years and those aged between 70-74 years. Gandara et al. found that Japanese patients had higher TTP and OS than European and American patients when treated with the same paclitaxel/carboplatin regimen in first-line chemotherapy for NSCLC, suggesting that Asian patients may be the race with greater benefit from chemotherapy. This conclusion is further supported by the results of the Asian subgroup of the JMDB phase I clinical study. Orlando et al. found that Asian NSCLC patients treated with the same regimen had significantly better OS than the overall population; 17.1 months for pemetrexed/cisplatin OS and 16.5 months for gemcitabine/cisplatin regimen. 2, chemotherapy combined with targeted therapy The effectiveness of first-line chemotherapy in advanced NSCLC has reached a plateau, and the simplest measure to further improve the efficacy is targeted combination chemotherapy. In recent years, many clinical studies have explored the efficacy of targeted drugs in combination with chemotherapy, most of which ended in failure, with only bevacizumab and cetuximab being successful. The 2009 ASCO study also reported the results of several targeted drug combination chemotherapy studies. The safety of bevacizumab in combination with a two-drug regimen was confirmed by the AVAIL phase I study and the SAIL large sample study. Gandara et al. investigated the safety of cetuximab + bevacizumab in combination with paclitaxel/carboplatin in the first-line treatment of advanced NSCLC. A total of 110 patients were included in the group, 104 were evaluable for toxicity and 95 for efficacy. 51 achieved partial remission; 22 were stable, with an overall disease control rate of 77%. The median follow-up was 15 months, with progression-free survival of 7 months and 18 cases maintained progression-free; OS was 14 months, with a 1-year survival rate of 57%.Bonomi et al. reported a phase I study of cetuximab + brivasumab in combination with paclitaxel/carboplatin for the first-line treatment of advanced NSCLC. 6 cycles of chemotherapy were used in group A and 3 cycles in group B. The primary study endpoint was PFS. The objective remission rate was similar in both groups, 31% in group A and 30% in group B. The results showed that the PFS was 6.0 months in group A and 4.2 months in group B, with an HRO of 57. The question of how to select patients who may effectively receive cetuximab in combination with chemotherapy has received much attention. 2009 ASCO, three studies examined biomarkers predicting clinical efficacy of cetuximab, all suggesting that KRAS mutations do not affect the efficacy of cetuximab. o'Byrne et al. analyzed 554 KRAS mutations in tumor specimens from the FLEX study population. There was no significant difference in cetuximab efficacy between the KRAS mutation and wild-type subgroups. The only clinical marker predictive of cetuximab efficacy indicated rash within 3 weeks of treatment, with OS more than 1-fold prolonged in patients with rash compared to those without rash. The results of FAST-ACT, a phase I randomized double-blind controlled study of erlotinib combined with chemotherapy as first-line treatment sequentially in Asian patients with stage IV NSCLC, showed a median PFS of 31.3 weeks vs. 23.7 weeks in the oral erlotinib group compared to patients in the placebo group, with an increased objective tumor remission rate and time-related non-progressive benefit, but no statistical difference, from which we can see Chemotherapy combined with sequential oral erlotinib can significantly prolong the PFS of patients. 3. Maintenance therapy Advanced NSCLC has reached a plateau not only with first-line chemotherapy but also with second-line chemotherapy. The efficacy of polytene paclitaxel and pemetrexed in second-line application is similar, with objective remission rate <10%, PFS around 3 months and OS of 6-7 months. The JMEN study compared the efficacy and safety of pemetrexed with placebo in stage IV NSCLC that had not progressed on 4 cycles of platinum-containing induction chemotherapy, and the pemetrexed maintenance group showed significantly improved PFS and OS. PFS and OS were significantly improved in the pemetrexed maintenance group, suggesting that pemetrexed as maintenance therapy can significantly prolong the survival of patients who benefit from first-line chemotherapy with a good safety profile. Also, it was shown that the efficacy of pemetrexed was histologically type-dependent and that patients with tumor types other than large cell and squamous carcinoma could benefit from it.Fidias et al. reported the efficacy and safety of immediate second-line treatment with doxorubicin in patients randomized to first-line chemotherapy who achieved disease remission or stabilization, and found that early doxorubicin use was more beneficial than late doxorubicin use benefited patients, with median PSF prolonged from 2.7 months to 5.7 months in the second-line application group and OS prolonged from 9.7 months to 12.3 months without more adverse effects. Further analysis of the data suggested that more patients in the maintenance group were able to receive treatment, while about 1/3 of the delayed treatment group failed to receive treatment for various reasons, and there was no significant difference in OS between the maintenance group and the patients in the delayed treatment group who actually received treatment, which was similar. However, there is no denying that maintenance therapy allows more patients to be treated, and this is the reason why maintenance therapy has gained more attention. 4. Histologic type and efficacy Lung cancer is usually divided into two categories: small cell lung cancer and non-small cell lung cancer (NSCLC) in previous clinical trials, and both have different chemotherapy regimens and treatment strategies. However, the publication of the results of the JMDB randomized phase III clinical study suggests that from now on, at least the histological types of NSCLC should be divided into squamous and non-squamous carcinomas; patients with non-squamous carcinomas can be treated from pemetrexed/cisplatin first-line chemotherapy regimens. cisplatin first-line chemotherapy regimens, while no difference in efficacy by tissue type was seen with other standard first-line chemotherapy regimens. In the JMDB study, 11.8 months for non-squamous cancer was significantly longer than the 10.4 months in the gemcitabine group. The results of the East Asian population study were similar, with an OS of 22.2 months, which was better than the 17.5 months of the gemcitabine/cisplatin regimen. IPASS is a randomized controlled phase III clinical study comparing the efficacy and safety of paclitaxel/carboplatin with gefitinib in the first-line treatment of Asian patients with non-smoking or less smoking lung adenocarcinoma, with the primary endpoint of PSF. The objective tumor remission rate was significantly higher. Further, molecular marker analysis suggested that EGFR genotype was a major factor influencing the efficacy of gefitinib. Patients with the mutation had significantly longer PSF with gefitinib than with chemotherapy, while patients with EGFR wild type had significantly lower efficacy than chemotherapy with gefitinib monotherapy, with only placebo-like efficacy and median PFS of only about 8 weeks, while chemotherapy efficacy was not affected by EGFR genotype. Therefore, chemotherapy should be preferred for EGFR wild-type patients. It is not appropriate to select patients for first-line treatment with gefitinib solely on the basis of clinical characteristics, because about 40% of this highly selective patient population still has tumors with wild-type EGFR. From a molecular perspective we can divide NSCLC into at least EGFR mutant type, EGFR wild type EGFR unknown type, and EGFR genotype unknown should be treated according to EGFR wild type. 6.Individualization of chemotherapy The way out of chemotherapy in the future should be individualization. The response to chemotherapy varies widely among patients and different tissue types of NSCLC. About 1/3 of patients can obtain tumor remission from current chemotherapy, about 1/3 of patients obtain disease stabilization, and another 1/3 of patients obtain progression. This variation cannot be explained by factors such as histological type, functional status of organs, age, and gender. First-line molecular markers are known to predict the efficacy of chemotherapy, and current studies have focused on DNA repair genes, oncogenes, oncogenes and patient genetic characteristics. ERCCL is a rate-limiting enzyme that plays an important role in the recognition and excision of platinum-induced DNA adducts, as well as in DNA cross-linking repair and recombination. In a study of correlation between ERCCL and chemotherapy efficacy, the efficiency of ERCCL mRNA low expression group with application of docetaxel + carboplatin was significantly higher than that of high expression group in the control group, suggesting that high ERCCL expression is associated with platinum resistance and therefore specific chemotherapy regimens should be selected according to ERCCL expression. It was shown that the expression of RRMI, a nucleotide reductase subunit that is the target of gemcitabine action, was also associated with the efficacy of gemcitabine, so a prospective phase I clinical study divided patients into RRMI high and low expression groups, which were further divided into high and low expression groups according to ERCCL, and selected chemotherapy regimens according to the characteristics of the phase I molecular markers; RRMI high expression ERCCL high expression group. RRMI high expression ERCCL low expression group, RRMI low expression ERCCL high expression group, and RRMI high expression ERCCL high expression group. The results showed a median OS of 13.3 months, PER of 6.6 months, and a disease efficiency of 42%, which resulted in a more substantial improvement in the efficacy of the study compared with historical controls. It also suggests that it is feasible to select chemotherapy regimens for first-line treatment of advanced NSCLC based on 1 or 2 gene expression levels, and can further improve the efficacy. Summary In conclusion, first-line chemotherapy for advanced NSCLC has made great progress in recent years, and the compliance, tolerability and efficacy of chemotherapy have improved compared with older generation regimens. Pemetrexed maintenance therapy has shown better tolerability and improved survival, and pemetrexed combined with platinum has become the standard first-line chemotherapy regimen for advanced NSCLC with a better safety profile and significantly prolonged overall survival in patients with non-squamous cancers. Combination targeted therapy is the development direction of chemotherapy to further improve the efficacy of NSCLC, and both bevacizumab and cetuximab combined with chemotherapy have significantly improved the overall survival. Genetic testing will gradually guide clinical treatment.