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
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Minghui Zhang1,*, Hongsheng Guo2,*, Shu Zhao1,*, Yan Wang3, Maopeng Yang1, Jiawei Yu1, Yubo Yan1, Yan Wang1
1Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
2Department of Medical Oncology, Tianjin Third Central Hospital, Tianjin, 300170, China
3Department of Medical Oncology, Heilongjiang Provincial Hospital, Harbin, 150000, China
*These authors are contributed equally to this work
Yan Wang, email: [email protected]
Keywords: non-small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor, overall survival
Received: October 30, 2015 Accepted: April 16, 2016 Published: May 20, 2016
The role of a combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy for non-small-cell lung cancer (NSCLC) has not been well established. To clarify this problem, we performed a meta-analysis with 15 studies identified from PubMed, EMBASE and the Cochrane Library. We found that the combined regimen had a significant benefit on progression-free survival (PFS) (hazard ratio (HR) = 0.80; 95% CI = 0.71–0.90; P < 0.001) and the objective response rate (ORR) (RR = 1.35; 95% CI = 1.14–1.59; P < 0.001). However, the combined regimen had no significant impact on overall survival (OS) (HR = 0.96; 95% CI = 0.90–1.03; P = 0.25). Subgroup analysis showed significantly higher OS advantages in EGFR mutation positive patients (P = 0.01), never smokers (P = 0.01), Asian patients (P = 0.02), patients receiving second-line treatment (P < 0.001), and those receiving a sequential combination of EGFR-TKIs and chemotherapy (P = 0.005). The combination regimen showed a higher incidence of grade 3–4 toxicities (leucopenia, neutropenia, febrile neutropenia, anemia, rash, fatigue and diarrhea). In summary, the combination of EGFR-TKIs plus chemotherapy in advanced NSCLC achieved a significantly longer PFS and a higher ORR but not longer OS. Well-designed prospective studies are needed to confirm these findings.
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