| Background:Lung cancer is almost the leading cause of cancer-related death in the industrialized world. Based on the latest global cancer statics, lung cancer accounting for17%of the total new cancer cases and23%of the total cancer deaths. The majority of these patients would be non-small-cell lung cancer (more than85%). However, since the symptoms are not specific during early periods, most patients have advanced disease (stage ⅢB with malignant pleural effusion or stage IV according to the previous staging system, now both included as stage IV in the revised system) at the time of initial diagnosis.Platinum-doublet chemotherapy, the first-line treatment for advanced NSCLC, gained a median overall survival (OS) of8-11months. After4-6cycles of treatment, patients without progression are observed until progress and then the second-line treatment is employed. Recently, a novel treatment named maintenance therapy, which means continuing to administer at least one of the initial regimens(continuation maintenance) or another active agents(switch maintenance) immediately after first-line chemotherapy until disease progression, unacceptable toxicity or a predefined number of cycles for patients who achieved at least stable disease after first-line chemotherapy, begins to emerge.Objectives:Although the therapeutic options have made great progress for these patients, the overall outcome remains poor. During last few years, many randomized clinical trials (RCTs) achieved encouraging results which provided more interests in maintenance therapy. However, controversies remain existed in the area wheter maintenance therapy can prolong the overall survival, improve the quality of life and induce more adverse effects during the therapy. We searched for randomized controlled trials to compare maintenance therapy with observation or placebo. The data were pooled and reported as hazard ratio (HR). The primary outcome was overall survival (OS) and secondary outcomes included progression free survival (PFS), objective response rate, and the proportion of patients received second-line therapy.Methords:We searched biomedical literature databases, conference proceedings and published reviews for randomized controlled trials to compare maintenance therapy with observation or placebo. A meta-analysis was conducted using STATA (Version12.0). The data were pooled and reported as hazard ratio (HR). The primary outcome was overall survival (OS).Results:Nineteen trials were included for final analysis with a total of5783patients. Maintenance therapy significantly improved OS and PFS. Maintenance therapy for Asians was slightly less effective in prolonging survival compared with Caucasians (Asians, HR,0.904,95%CI,0.745-1.097; Caucasian, HR,0.856,95%CI0.788-0.930,). Maintenance therapy for adenocarcinoma was mild superior in improving OS to non-adenocarcinoma (adenocarcinoma, HR0.807,95%CI0.685-0.951; non-adenocarcinoma, HR0.924,95%CI0.774-1.103). Adverse effects were greater in maintenance therapy. In addition, the patients who were able to receive second-line therapy were less in maintenance arm. Maintenance therapy with EGFR-TKI or pemetrexed produced significant impact on progression-free survival (EGFR-TKI, HR,0.636,95%CI,0.491-0.823,p=0.001; Pemetrexed, HR0.551,95%CI0.471-0.646,p<0.001). However, maintenance therapy with gemcitabine did not produce a statically significant improvement in overall survival (HR0.883,95%CI0.725-1.076, p=0.217) and progression-free survival (HR0.711;95%CI0.481-1.05; p=0.087) compared with best supportive care or observationConclusion:Maintenance therapy for advanced Caucasian adenocarcinoma patients showed superiority in OS and PFS. The effect of EGFR-TKIs and pemetrexed is superivor over gemcitabine. More clinical trials are still needed to clarify the strategies and effects of maintenance therapy in the future. |
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