EGFR Tyrosine Kinase Inhibitor (TKI) Combined With Concurrent or Sequential Chemotherapy for Patients With Advanced Lung Cancer and Gradual Progression After First-Line EGFR-TKI Therapy: A Randomized Controlled Study

Abstract

The aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation.A systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7 th , 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 HR of PFS and OS was 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 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 chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy 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 chemotherapy-induced toxicities that is well tolerated and clinically manageable.

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…From the first-line and second-line therapy to consolidation therapy, immunotherapy has shown great potential in the individualized and precise treatment of lung cancer [29]. Malignant tumor cells can express PD-L1 through two mechanisms: one is congenital immune resistance, that is, in some tumors, component carcinogenic signal transduction directly upregulates the expression of PD-L1 on all tumor cells, which is a genetic event and has nothing to do with inflammatory stimulation [30][31][32]. The second is adaptive immune resistance, that is, the expression of PD-L1 induced by inflammatory signals (such as interferon γ) generated by antitumor immune response [33].…”

Combination of anlotinib and gemcitabine promotes the G0/G1 cell cycle arrest and apoptosis of intrahepatic cholangiocarcinoma in vitro

“…11 However, clinical practice has shown that a single drug small-molecule TKI has a limited therapeutic effect, and combined chemotherapeutic drugs can significantly improve their anti-tumor effect. 12,13 Currently, studies have shown that targeted drugs combined with chemotherapy drugs can significantly improve the efficacy of anti-tumor therapy. 14 Due to the combination of targeted drugs and reduced dose of chemotherapeutic drugs, patients have better tolerance to anti-tumor therapy and better treatment compliance, thus achieving the purpose of low-toxicity and high-efficiency anti-tumor therapy.…”

“…12,13 Currently, studies have shown that targeted drugs combined with chemotherapy drugs can significantly improve the efficacy of anti-tumor therapy. 14 Due to the combination of targeted drugs and reduced dose of chemotherapeutic drugs, patients have better tolerance to anti-tumor therapy and better treatment compliance, thus achieving the purpose of low-toxicity and high-efficiency anti-tumor therapy. 15 According to this view, the hypothesis of this study is that gemcitabine is a cell cycle-specific chemotherapy drug.…”

“… 11 However, clinical practice has shown that a single drug small‐molecule TKI has a limited therapeutic effect, and combined chemotherapeutic drugs can significantly improve their anti‐tumor effect. 12 , 13 …”

“…Anlotinib was approved as a third‐line treatment for locally advanced or metastatic non‐small cell lung cancer (NSCLC) in a randomized, double‐blind clinical trial, ALTER0303 11 . However, clinical practice has shown that a single drug small‐molecule TKI has a limited therapeutic effect, and combined chemotherapeutic drugs can significantly improve their anti‐tumor effect 12,13 …”