Combination of chemotherapy and gefitinib as first-line treatment for patients with advanced lung adenocarcinoma and sensitive EGFR mutations: A randomized controlled trial

Han, Baohui; Jin, Bo; Chu, Tianqing; Niu, Yiming; Dong, Yu; Xu, Jianlin; Gu, Anzhong; Zhong, Hua; Wang, Huimin; Zhang, Xueyan; Shi, Chunlei; Zhang, Yanwei; Zhang, Wei; Lou, Yu‐Qing; Zhu, Lei; Pei, Jiao

doi:10.1002/ijc.30806

Cited by 117 publications

(112 citation statements)

References 34 publications

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“…Given that significant discrepancy results of Keynote-024 and Checkmate-026 [29,180], only highly selective patients should be available for a single agent in the first-line setting. Back to the era of targeted therapy, combination strategies have achieved great success, and theoretically, this may probably work out in checkpoint inhibitors [181][182][183]. Keynote-021 first reported preliminary results of checkpoint inhibitors combined with chemotherapy [180].…”

Section: Checkpoint Inhibitors Pembrolizumab Nivolumab and Atezolizmentioning

confidence: 99%

Emerging therapies for non-small cell lung cancer

et al. 2019

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Recent advances in the field of novel anticancer agents prolong patients' survival and show a promising future. Tyrosine kinase inhibitors and immunotherapy for lung cancer are the two major areas undergoing rapid development. Although increasing novel anticancer agents were innovated, how to translate and optimize these novel agents into clinical practice remains to be explored. Besides, toxicities and availability of these drugs in specific regions should also be considered during clinical determination. Herein, we summarize emerging agents including tyrosine kinase inhibitors, checkpoint inhibitors, and other potential immunotherapy such as chimeric antigen receptor T cell for non-small cell lung cancer attempting to provide insights and perspectives of the future in anticancer treatment.

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Section: Checkpoint Inhibitors Pembrolizumab Nivolumab and Atezolizmentioning

confidence: 99%

Emerging therapies for non-small cell lung cancer

et al. 2019

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“…Several studies have explored whether administration of TKIs in combination with chemotherapy can prolong PFS and OS in patients with advanced lung adenocarcinoma and sensitive EGFR mutations. For example, Han et al found that gefitinib given together with chemotherapy resulted in a longer PFS than either chemotherapy or gefitinib alone [9]. Moreover, in patients with advanced lung adenocarcinoma and sensitive EGFR mutations, the NEJ005 study found that both PFS and OS were extended by concurrent combined treatment with gefitinib and chemotherapy [10,11] compared with the PFS and OS achieved with TKI monotherapy [12].…”

Section: Introductionmentioning

confidence: 99%

Combination of icotinib and chemotherapy as first-line treatment for advanced lung adenocarcinoma in patients with sensitive EGFR mutations: A randomized controlled study

Qin

Zhang

et al. 2019

Lung Cancer

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To explore the efficacy and safety of icotinib with chemotherapy as first-line therapy for advanced lung adenocarcinoma in patients with sensitive epidermal growth factor receptor (EGFR) mutations. Methods: This prospective, randomized, controlled trial was conducted in 10 general hospitals in Shandong Province, China. Previously untreated patients with advanced lung adenocarcinoma and sensitive EGFR mutations were recruited between January 16, 2014 and December 31, 2016 and randomly allocated to the combination group (icotinib plus pemetrexed and carboplatin) or the icotinib only group. The patients were followed up until May 23, 2018. The primary endpoint was progression-free survival (PFS). Results: The efficacy analysis (intention-to-treat analysis) include 179 patients (n = 90 in the combination group and n = 89 in the icotinib only group). PFS was significantly longer in the combination group than in the icotinib only group (16.0 months vs. 10.0 months, hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.42-0.84, P = 0.003). The objective response rate and the disease control rate for the combination group were significantly higher than those for the icotinib only group (77.8% vs. 64.0%, χ 2 = 4.094, P = 0.043; 91.1% vs. 79.8%, χ 2 = 4.632, P = 0.031). However, overall survival did not differ between the two groups (36.0 months vs. 34.0 months, HR = 0.81, 95%CI 0.54-1.22, P = 0.309). The incidence rates of leukopenia and liver function damage of grades 3-4 were higher in the combination group than in the icotinib only group (12.2% vs. 0%, χ 2 = 11.086, P = 0.001; 12.2% vs. 3.5%, χ 2 = 4.488, P = 0.034). However, adverse events were resolved in most patients. Conclusion: Use of the combination of icotinib and chemotherapy as first-line therapy significantly improved the PFS of advanced lung adenocarcinoma patients with sensitive EGFR mutations. Although the combination therapy increased the incidence of leukopenia and liver function damage, the observed adverse events were tolerable and manageable.

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“…Of these potential studies, 13 studies were excluded because of retrospective studies [14][15][16][17], unselected EGFR mutation [18][19][20][21], single arms [22][23][24], small sample size [25], and insufficient survival data [26]. Finally, eight studies comparing EGFR-TKI plus chemotherapy with EGFR-TKI alone as first-line treatment in advanced non-small cell lung cancer with activating EGFR mutation were included in this meta-analysis [8,[27][28][29][30][31][32][33]. The flow diagram of studies selection was summarized in Fig 1.…”

Section: Study Selectionmentioning

confidence: 99%

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

Luo²,

Wen

et al. 2020

Preprint

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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.

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Combination of chemotherapy and gefitinib as first-line treatment for patients with advanced lung adenocarcinoma and sensitive EGFR mutations: A randomized controlled trial

Cited by 117 publications

References 34 publications

Emerging therapies for non-small cell lung cancer

Emerging therapies for non-small cell lung cancer

Combination of icotinib and chemotherapy as first-line treatment for advanced lung adenocarcinoma in patients with sensitive EGFR mutations: A randomized controlled study

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

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