Abstract
Object. This study is aimed at evaluating the efficacy and safety of pemetrexed and gefitinib in the treatment of non-small-cell lung cancer (NSCLC). Methods. Databases, including PubMed, the Cochrane Library, Embase, CNKI, and Web of Science, were applied to search for randomized controlled trials (RCTs) about the use of pemetrexed and gefitinib in the second-line treatment of locally advanced and metastatic NSCLC from database foundation to April 2020. Meta-analysis was conducted using the RevMan 5.3 software. Primary outcomes included progression-free survival (PFS) and overall survival (OS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and all grades of drug-related adverse events (AEs). Results. Totally, 14 RCTs and 1,334 patients were involved in the study. The results of meta-analysis showed that compared with pemetrexed, gefitinib was not superior in improving ORR ( P = 0.21 ), DCR ( P = 0.52 ), PFS ( P = 0.41 ), and OS ( P = 0.79 ). Subgroup analysis showed that in patients with mutant EGFR ( P = 0.08 ) and wild-type EGFR ( P = 0.80 ), both pemetrexed and gefitinib produced a similar effect on PFS. In terms of safety, the incidence of rash ( P < 0.00001 ) and diarrhea ( P = 0.0005 ) in the gefitinib group was significantly higher than those in the pemetrexed group, while the occurrence of neutropenia ( P = 0.01 ) and fatigue ( P = 0.02 ) was significantly lower. Conclusion. Gefitinib and pemetrexed showed similar efficacy and safety, regardless of the type of EGFR. Both gefitinib and pemetrexed can be used as conventional drugs for the second-line treatment of locally advanced and metastatic NSCLC.
Highlights
Lung cancer remains the leading cause of cancer-related deaths worldwide [1]
Gefitinib cannot be used in all patients with advanced Non-small-cell lung cancer (NSCLC), and its efficacy is more obvious in the benefit population
Here, we found that for patients with EGFR mutation-positive NSCLC, gefitinib was not superior to pemetrexed in terms of progression-free survival (PFS), which might be related to the predominance of the patients who smoked, had adenocarcinoma, had EGFRsensitive mutation-negative NSCLC, or had unknown mutations in all included studies
Summary
Non-small-cell lung cancer (NSCLC) is the most common type, accounting for about 80%-85% of all lung cancers [2]. Platinum-based chemotherapy is used as the standard firstline chemotherapy regimen at present for advanced NSCLC [3], but it can only take effect on 30%-40% of patients and contribute to a median survival time of only 8 to 11 months [4]. Compared with the optimal supportive treatment, platinum-based chemotherapeutics can improve patient’s overall survival (OS) and progression-free survival (PFS). Most patients will develop drug resistance after several periods of platinum-based first-line chemotherapy, on which occasion second-line chemotherapy is recommended [5]. Second-line chemotherapeutics mainly include docetaxel, pemetrexed, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) (gefitinib and erlotinib) [6].
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