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First-generation EGFR-TKI plus chemotherapy versus EGFR-TKI alone as first-line treatment in advanced NSCLC with EGFR activating mutation: a systematic review and meta-analysis of randomized controlled trials

By Qiang Wu, Wuxia Luo, Wen Li, Ting Wang, Lin Huang, Feng Xu

Posted 17 Apr 2020
bioRxiv DOI: 10.1101/2020.04.17.046409

The role of addition of chemotherapy (CT) to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for EGFR-mutated non-small cell lung cancer (NSCLC) has not been well established. The aim of this meta-analysis was to evaluate efficacy and toxicity of EGFR-TKI in combination with CT compared to EGFR-TKI monotherapy as first-line treatment in advanced NSCLC harboring EGFR activating mutation. A systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. A total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) were 0.56 (95% CI=0.50-0.64; P < 0.00001) and 0.70 (95% CI=0.54-0.90; P=0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P=0.02) and concurrent therapy (P=0.002). The objective response rate (ORR) in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10–1.26). The combination regimen showed a higher incidence of CT-induced toxicities. Subgroup analysis indicated that doublet CT rather than single-agent CT significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia. In conclusion, compared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC, yet at the price of increasing incidence of CT-induced toxicities that is well tolerated and clinically manageable.

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