Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

Zhang, Minghui; Guo, Hongsheng; Song, Zhao; Wang, Yan; Mi, Yang; Yu, Jiang; Yan, Yubo

doi:10.18632/oncotarget.9503

Cited by 9 publications

(7 citation statements)

References 45 publications

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“…De-escalated dosages of afatinib showed a greater tendency towards longer periods of TTF in this study (Figure 2 ). These results are consistent with the results of other trials of afatinib therapy [ 6 , 13 , 14 , 15 ]. The suspension of high-dosage afatinib therapy usually stems from the occurrence of higher grade diarrhea and cutaneous toxicity as adverse events.…”

Section: Discussionsupporting

confidence: 92%

The efficacy of 40 mg versus dose de-escalation to less than 40 mg of afatinib (Giotrif) as the first-line therapy for patients with primary lung adenocarcinoma harboring favorable epidermal growth factor mutations

Liu

Wang

et al. 2017

Oncotarget

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The choice of a first-line therapy for lung cancer is a crucial decision that can impact the survival as well as the quality of life of a patient. Inhibitors of epidermal growth factor receptor (EGFR) such as afatinib, erlotinib, and gefitinib have previously been used to treat non-small cell lung cancer harboring favorable EGFR mutations. Although afatinib has greater efficacy than other EGFR inhibitors, adverse events related to its use can result in the discontinuation of the therapy. In this study, we compared the therapeutic efficacy in lung cancer patients of a regimen of 40 mg/day of afatinib with that of a lower dose regimen of <40 mg/day resulting either from a lower starting dose of 30 mg/day or dose adjustment. Seventy-nine patients were treated with 40 mg/day and 67 received de-escalated doses of <40 mg/day. There was no significant difference in the clinical characteristics of the two groups except that the proportion of patients with a body weight of 50 kg or more was greater in the 40 mg/day group. Otherwise, there were no significant differences between the two groups in the average time to treatment failure (TTF), the rates at which the administration of a second-line therapy was necessary, or the frequency and severity of adverse events. Overall, these results suggest that it is possible to calibrate the dosage of afatinib to suit individual patient parameters such as low body weight, and that such calibration can be advised based on the given patient’s individual experience of the drug.

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Section: Discussionsupporting

confidence: 92%

The efficacy of 40 mg versus dose de-escalation to less than 40 mg of afatinib (Giotrif) as the first-line therapy for patients with primary lung adenocarcinoma harboring favorable epidermal growth factor mutations

Liu

Wang

et al. 2017

Oncotarget

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“…benefit was shown in EGFR mutation-positive patients by subgroup analysis (10). Cheng et al also demonstrated that the addition of pemetrexed to gefitinib in first-line treatment improved PFS compared with gefitinib alone in Ease Asian patients with advanced EGFR-mutant lung cancer (HR, 0.68; 95% CI, 0.48 to 0.96; one-sided P=0.014; two-sided P=0.029) (11).…”

Section: Editorialmentioning

confidence: 98%

The continued EGFR-TKI with cytotoxic chemotherapy at progression—poison or medicine?

Yoon

Choi

Lee

2018

Transl. Lung Cancer Res.

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“…In patients whose tumours harbours an activating EGFR mutation, EGFR TKIs should be used as first-line therapy [ 6 – 9 ], whereas for the rest of NSCLC cases, standard treatment currently consists of platinum-based doublet chemotherapy. Gefitinib, erlotinib and afatinib show higher response rates and longer progression free survival than chemotherapy in those patients, as tested in several clinical trials exhibiting consistent results [ 10 – 20 ], all of them favouring the target therapy.…”

Section: Introductionmentioning

confidence: 98%

Comparative outcome assessment of epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small-cell lung cancer: a network meta-analysis

et al. 2017

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IntroductionTyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced non-small–cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection.Materials And MethodsWe performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC. Cochrane guidelines were used for statistical analysis.Results3,179 patients were included. All EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR for gefitinib, erlotinib and afatinib were 52.1%, 67.3% and 61.6% respectively. HRs for PFS were 0.62 (95% CI, 0.38–1.00) for gefitinib, 0.28 (95% CI, 0.17–0.45) for erlotinib and 0.40 (95% CI, 0.20–0.83) for afatinib. HRs for OS were not statistically significant for any agent.ConclusionsOur results suggest similar clinical efficacy and higher toxicity of Afatinib treatment. As this still remains the agent with best CSF penetration, we suggest its use is limited to patients presenting with brain metastasis. We suggest the use of Gefitinib in patients without CNS involvement. Faced with the impossibility to dose-reduce Gefitinib, Erlotinib represents a tolerable and effective alternative to Afatinib and Gefitinib if response to EGFR inhibition is considered still effective.

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Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

Cited by 9 publications

References 45 publications

The efficacy of 40 mg versus dose de-escalation to less than 40 mg of afatinib (Giotrif) as the first-line therapy for patients with primary lung adenocarcinoma harboring favorable epidermal growth factor mutations

The efficacy of 40 mg versus dose de-escalation to less than 40 mg of afatinib (Giotrif) as the first-line therapy for patients with primary lung adenocarcinoma harboring favorable epidermal growth factor mutations

The continued EGFR-TKI with cytotoxic chemotherapy at progression—poison or medicine?

Comparative outcome assessment of epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small-cell lung cancer: a network meta-analysis

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