Meta-analysis of Seven Randomized Control Trials to Assess the Efficacy and Toxicity of Combining EGFR-TKI with Chemotherapy for Patients with Advanced NSCLC who Failed First-Line Treatment

Xiao, Bing-Kun; Yang, Jian-Yun; Dong, Jun-Xing; Ji, Zhao-Shuai; Si, Hai-Yan; Wang, Wei-Lan; Huang, Rong-Qing

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자료유형: 학술저널

저자정보: Xiao, Bing-Kun (Department of Pharmacochemistry, Institute of Radiation Medicine) Yang, Jian-Yun (Department of Pharmacochemistry, Institute of Radiation Medicine) Dong, Jun-Xing (Department of Pharmacochemistry, Institute of Radiation Medicine) Ji, Zhao-Shuai (Department of Pharmacy, Beijing Tsinghua Changgung Hospital) Si, Hai-Yan (Department of Oncology, Chinese PLA General Hospital) Wang, Wei-Lan (Department of Pharmaceutical Care, Chinese PLA General Hospital) Huang, Rong-Qing (Department of Pharmacochemistry, Institute of Radiation Medicine)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제7호

발행연도: 2015.1

수록면: 2,915 - 2,921 (7page)

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Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR- TKI with chemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trials are inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKI and chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods: We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library and Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression- free survival (PFS), overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis, covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR 1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR 0.88 [0.68-1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS (HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05-2.21], p=0.03). However, combination therapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improved the ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62-0.88], p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade 3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combination therapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic and predictive factors to find the group with the highest benefit of the combination strategy.

#EGFR-TKI #chemotherapy #non-small cell lung cancer #meta-analysis #RCTs

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