Comparison of gefitinib plus chemotherapy versus gefitinib alone for advanced non-small-cell lung cancer: A meta analysis

Yi, Min; He, Ting; Wang, Kaijin; Wei, Yonggang

doi:10.1016/j.clinsp.2022.100152

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Review articles • Clinics 78 • 2023 • https://doi.org/10.1016/j.clinsp.2022.100152 copy

Comparison of gefitinib plus chemotherapy versus gefitinib alone for advanced non-small-cell lung cancer: A meta analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

This study aimed to perform a meta-analysis comparing the efficacy and safety of gefitinib in combination with chemotherapy versus gefitinib alone in patients with advanced Non-Small Cell Lung Cancer (NSCLC). We searched databases for clinical studies that reported the efficacy or safety of gefitinib plus chemotherapy in comparison with gefitinib alone. Raw data from included studies were extracted and pooled to calculate the Odds Ratio (OR) for Objective Response Rate (ORR) and Disease Control Rate (DCR), the Hazard Ratio (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), and OR for complication ≥ Grade 3. A total of 10 studies containing 1,528 patients with NSCLC were identified and included in the analysis. Gefitinib plus chemotherapy showed significantly better efficacy in improving ORR (OR = 1.54; 95% CI [Confidence Interval], 1.13‒2.1; p = 0.006), DCR (OR = 1.62; 95% CI 1.14‒2.29; p = 0.007), PFS (HR=1.67; 95% CI 1.45‒1.94; p < 0.001) and OS (HR = 1.49; 95% CI 1.2‒1.87; p < 0.001) as compared with gefitinib alone. Consistent results were observed in the sub-population with positive EGFR mutation. The combination of gefitinib with chemotherapy had a significantly higher risk of complication (≥ Grade 3) with an OR of 3.29 (95% CI 2.57‒4.21; p < 0.001). The findings in the present study suggest that the combination of gefitinib with chemotherapy can provide better disease response and survival outcomes for patients with advanced NSCLC.

Keywords:
NSCLC; Gefitinib; Chemotherapy; Objective response rate; Disease control rate; Progression-free survival; Overall survival; Complication

HIGHLIGHTS

This meta-analysis shows that gefitinib plus chemotherapy showed significantly better efficacy in improving objective response rate, disease control rate, progression-free survival, and OS as compared with gefitinib alone.

Similar efficacy of gefitinib plus chemotherapy is found in the sub-population with positive EGFR mutation.

The toxicity of gefitinib plus chemotherapy is also increased but within clinical management.

Study ID	Study location	Rate of EGFR mutation	Type of tumor	Stage of cancer	Special type of population	Prospective and randomized	Combined treatment	Number of patients	Previous treatment
2007 Chen¹⁶16 Chen YM, Liu JM, Chou TY, Perng RP, Tsai CM, Whang-Peng J. Phase II randomized study of daily gefitinib treatment alone or with vinorelbine every 2 weeks in patients with adenocarcinoma of the lung who failed at least 2 regimens of chemotherapy. Cancer 2007;109(9):1821–8.	China	50%	Lung adenocarcinoma	IV	None	Yes	Vinorelbine	48	previous chemotherapy with > = 2 regimens
2011 Chen¹⁷17 Chen YM, Fan WC, Tsai CM, Liu SH, Shih JF, Chou TY, et al. A phase II randomized trial of gefitinib alone or with tegafur/uracil treatment in patients with pulmonary adenocarcinoma who had failed previous chemotherapy. J Thorac Oncol 2011;6 (6):1110–6.	China	67%	Lung adenocarcinoma	IIIB/IV	None	Yes	Tegafur/Uracil	115	failed previous chemotherapy
2014 and 2015 Yang¹⁹19 Yang JC, Kang JH, Mok T, Ahn MJ, Srimuninnimit V, Lin CC, et al. First-line pemetrexed plus cisplatin followed by gefitinib maintenance therapy versus gefitinib mono-therapy in East Asian patients with locally advanced or metastatic non-squamous non-small cell lung cancer: a randomised, phase 3 trial. Euro J Cancer 2014;50(13):2219– 30.,²⁴24 Yang JC, Srimuninnimit V, Ahn MJ, Lin CC, Kim SW, Tsai CM, et al. First-line pemetrexed plus cisplatin followed by gefitinib maintenance therapy versus gefitinib mono-therapy in east asian never-smoker patients with locally advanced or metastatic nonsquamous non-small cell lung cancer: final overall survival results from a randomized phase 3 Study. J Thorac Oncol 2016;11(3):370–9.,^a a The two studies by Yang et al. in 2014 and 2015 reported progression-free survival and overall survival of the same patient population, respectively. Thus, the two studies were considered as one in the present analysis. EGFR, Epidermal Growth Factor Receptor; NSCLC, Non-Small Cell Lung Cancer; N/A, Not Available.	Asian multicentre	68%	NSCLC	IIIB/IV	Nonsmoker/Light former smoker	Yes	Pemetrexed + cisplatin	236	chemonaive
2016 An²⁰20 An C, Zhang J, Chu H, Gu C, Xiao F, Zhu F, et al. Study of gefitinib and pemetrexed as first-line treatment in patients with advanced non-small cell lung cancer harboring EGFR Mutation. Pathol Oncol Res 2016;22(4):763–8.	China	100%	NSCLC	IIIB/IV	None	Yes	Pemetrexed	90	N/A
2016 Cheng²¹21 Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, et al. Randomized Phase II Trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol 2016;34(27):3258–66.	Asian multicentre	100%	Nonsquamous NSCLC	IV/Recurrent	None	Yes	Pemetrexed	191	no prior systemic chemotherapy, immunotherapy, or biologic therapy
2017 Han²²22 Han B, Jin B, Chu T, Niu Y, Dong Y, Xu J, et al. Combination of chemotherapy and gefitinib as first-line treatment for patients with advanced lung adenocarcinoma and sensitive EGFR mutations: a randomized controlled trial. Inter J Cancer 2017;141 (6):1249–56.	China	100%	Lung adenocarcinoma	IIIB/IV	None	Yes	Pemetrexed + Carboplatin	81	no prior systemic anticancer therapy for advanced disease
2019 Zhang²⁵25 Zhang YQ, Jiang LJ, Jiang SX, Xu YF, Zhou BB, Huang GH, et al. Gefitinib with or without transarterial infusion chemotherapy (cisplatin) for large nonsmall cell lung cancer with epidermal growth factor receptor mutations. J Vasc Inter Radiol 2019;30 (7):1004–12.	China	100%	NSCLC	III/IV	None	No	Cisplatin	92	no prior surgery, chemotherapy, radiotherapy, or immunotherapy
2019 Noronha²⁶26 Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, et al. Gefitinib versus gefitinib plus pemetrexed and carboplatin chemotherapy in egfr-mutated lung cancer. J Clin Oncol 2020;38(2):124–36.	India	100%	NSCLC	IIIB/IV	None	Yes	Pemetrexed + Carboplatin	334	N/A
2020 Hosomi¹⁸18 Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, et al. Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 Study. J Clin Oncol 2020;38(2):115–23.	Japan	100%	Nonsquamous NSCLC	IIIB/IV/Recurrent	None	Yes	Pemetrexed + Carboplatin	341	no prior chemotherapy

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[1] *Corresponding author. E-mail address:Weiyonggang_0208@yeah.net (Y. Wei).