Continuous chemotherapy and maintenance therapy The conventional first-line platinum-containing diphasic chemotherapy for advanced NSCLC is administered for 4-6 cycles, and the treatment ends with an observational follow-up period until disease progression before starting second-line therapy, with a median PFS of 4-6 months for patients. Therefore, the possibility of improving treatment efficacy by increasing the number of cycles of first-line chemotherapy has been suggested. a number of randomized phase III clinical trials comparing the efficacy of standard chemotherapy cycles followed by observation and extending the number of chemotherapy cycles until disease progression found that extending the number of chemotherapy cycles did not result in a survival benefit. a meta-analysis of 13 clinical studies including 3027 patients reported in 2009 suggested that extending the A meta-analysis including 3027 patients in a clinical study reported in 2009 suggested that extending the number of chemotherapy cycles resulted in a significant prolongation of PFS (HR: 0.75; 95% CI: 0.69-0.81; P<0.00001< span="">) but not OS (HR: 0.92; 95% CI: 0.86-0.99; P=0.03), and a subgroup analysis showed that choosing a regimen that included third-generation chemotherapy drugs PFS benefit was greater in patients with continuous treatment, but chemotherapy-related toxicities were also significantly increased. Zhiyong Ma, Department of Internal Medicine, Henan Cancer Hospital So, is it possible to improve the efficacy and prolong survival by choosing cytotoxic monotherapy with relatively less toxicity in patients who are effective after first-line platinum-containing diphasic regimen chemotherapy? This is the first time that the concept of maintenance therapy for lung cancer was proposed. The current research on maintenance therapy mainly includes original drug maintenance and drug exchange maintenance: original drug maintenance is to use a drug that has been used in first-line therapy for maintenance only in patients who have not progressed in first-line chemotherapy, thus avoiding the toxic side effects of combination chemotherapy; drug exchange maintenance is to use a drug that has not been used in first-line therapy for maintenance in the maintenance phase, thus avoiding the emergence of cross-resistance. The original maintenance therapy is the most consistent with the intention of maintenance therapy and was carried out earlier. The main maintenance drugs selected include paclitaxel and gemcitabine, but they did not achieve satisfactory clinical results. It was not until the release of survival data from the PARAMOUNT study at the 2012 ASCO Annual Meeting that the first prodrug maintenance therapy was able to extend survival time in patients with advanced NSCLC. This study enrolled 540 patients with advanced non-squamous NSCLC treated with 4 cycles of progression-free first-line pemetrexed/cisplatin regimen chemotherapy and randomized to receive pemetrexed as-is maintenance therapy or placebo, and showed that pemetrexed maintenance therapy significantly prolonged OS and reduced the risk of death by 22%, with a median OS of 16.9 months for patients in the maintenance group. phase III clinical study PointBreak compared the efficacy of first-line treatment with paclitaxel/carboplatin combined with bevacizumab followed by bevacizumab monotherapy with that of first-line treatment with pemetrexed/carboplatin combined with bevacizumab followed by pemetrexed combined with bevacizumab maintenance in patients with advanced non-squamous cancer, and found only a PFS benefit in the combined maintenance group, with no significant OS benefit. However, many investigators have questioned the results of the study due to the different first-line chemotherapy regimens in the two groups. Therefore, in the AVAPERL study, the efficacy of choosing bevacizumab monotherapy maintenance and pemetrexed combined with bevacizumab maintenance after first-line pemetrexed/cisplatin combined with bevacizumab was compared in patients with advanced non-squamous cancer, and it was finally demonstrated that patients in the combined maintenance group had significantly higher PFS and OS than those in the monotherapy maintenance group, with PFS of 7.4 months and 3.7 months, respectively, and median OS of 17.1 The median OS was 17.1 months and 13.2 months, respectively. Drugs frequently selected for maintenance in switchover studies include docetaxel, pemetrexed, erlotinib and gefitinib as maintenance drugs for standard second-line therapy. In a randomized phase III clinical study of immediate or delayed docetaxel treatment after first-line chemotherapy for advanced NSCLC, 566 patients were given 4 cycles of gemcitabine/carboplatin regimen and 309 patients who did not experience disease progression after treatment were randomized to the immediate docetaxel treatment group or the standard second-line treatment group. PFS was significantly better in patients receiving immediate docetaxel (5.7 vs 2.7 months; P = 0.0001), but OS was not significantly prolonged (12.3 vs 9.7 months; P = 0.0853). In the randomized phase III clinical study of pemetrexed switch maintenance therapy, 663 patients who received 4 cycles of third-generation agents combined with platinum-based first-line chemotherapy without progression were enrolled and randomly assigned to the pemetrexed monotherapy maintenance or placebo groups. The results found that both PFS and OS were significantly better in the maintenance treatment group compared with the placebo group, 4.3 vs 2.6 months (HR: 0.50; 95% CI: 0.42-0.61; P<0.00001< span="">) and 13.4 vs 10.6 months (HR: 0.79; 95% CI: 0.65-0.95; P = 0.012), respectively. Subgroup analysis further revealed a more pronounced prolongation of PFS and OS in non-squamous cancer patients receiving pemetrexed monotherapy maintenance. the SATURN study, a randomized phase III placebo-controlled clinical trial looking at the efficacy of erlotinib maintenance therapy in patients who were progression-free after first-line chemotherapy, enrolled 889 patients and found that compared with placebo, erlotinib maintenance therapy significantly improved patients’ PFS (HR: 0.71, P<0.0001< span="">) and OS (12 vs. 11 months, HR: 0.81; P=0.0088) compared with placebo. Subgroup analysis showed the greatest benefit in patients with EGFR mutations. As a result, pemetrexed and erlotinib were approved for maintenance therapy in patients with advanced NSCLC who had not progressed on first-line chemotherapy. Although, maintenance therapy studies have achieved milestones and changed clinical practice guidelines for patients with advanced NSCLC, the role of cytotoxic chemotherapeutic agents in maintenance therapy remains in question. In the randomized phase III clinical study of docetaxel immediate or delayed treatment, 37% of patients in the delayed group did not receive second-line chemotherapy, compared with 5.2% in the immediate treatment group. Notably, in this study, the OS of patients who received second-line therapy after disease progression in the delayed group was 12.5 months, as was that of patients treated with immediate docetaxel after first-line therapy, meaning that patients who were closely followed up to ensure appropriate second-line therapy after disease progression could also achieve good survival times. In the phase III study of pemetrexed maintenance therapy, 33% of patients in the observation group did not receive second-line chemotherapy after disease progression, and even among those who did receive second-line chemotherapy, only 19% used the pemetrexed regimen. These can lead to biased study results. Therefore, would it not be more scientific to recommend maintenance therapy based on the patient group with the greatest survival benefit in the subgroup analysis of the maintenance therapy study? For example, pemetrexed switch maintenance for non-squamous cancer patients who are stable after first-line chemotherapy, erlotinib for patients with EGFR mutations, etc. In the study of pemetrexed continuation maintenance therapy for non-squamous cancer patients, the current study confirmed that pemetrexed combined with bevacizumab is better than bevacizumab monotherapy, but whether it is better than pemetrexed monotherapy needs to be further confirmed by clinical studies. Another important point to note is the toxicity of maintenance therapy. In the JMEI study, a significantly higher incidence of malaise was found in the pemetrexed maintenance group compared to the observation group, and 5% of patients discontinued treatment due to toxicity.