吸烟状态对携带激活型表皮生长因子受体（EGFR）突变的非小细胞肺癌患者一线接受EGFR酪氨酸激酶抑制剂与铂类双联化疗的无进展生存期的影响：前瞻性随机试验的荟萃分析
The role of smoking status on the progression-free survival of non-small cell lung cancer patients harboring activating epidermal growth factor receptor (EGFR) mutations receiving first-line EGFR tyrosine kinase inhibitor versus platinum doublet chemotherapy: a meta-analysis of prospective randomized trials.
作者信息
Hasegawa Yoshikazu, Ando Masahiko, Maemondo Makoto, Yamamoto Satomi, Isa Shun-Ichi, Saka Hideo, Kubo Akihito, Kawaguchi Tomoya, Takada Minoru, Rosell Rafael, Kurata Takayasu, Ou Sai-Hong Ignatius
机构信息
Izumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA.
Izumi Municipal Hospital, Osaka, Japan; Nagoya University Hospital, Nagoya, Aichi, Japan; Miyagi Cancer Center, Miyagi, Japan; University of Kansas Cancer Center, Kansas City, Kansas, USA; National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; National Hospital Organization Nagoya Medical Center, Aichi, Japan; Aichi Medical University School of Medicine, Nagoya, Aichi, Japan; Graduate School of Medicine, Osaka City University, Osaka, Japan; Koyo Hospital, Wakayama, Japan; Catalan Institute of Oncology, Barcelona, Spain; Kansai Medical University Hirakata Hospital, Osaka, Japan; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, California, USA
出版信息
Oncologist. 2015 Mar;20(3):307-15. doi: 10.1634/theoncologist.2014-0285. Epub 2015 Feb 5.
BACKGROUND
Univariate analyses from several randomized phase III trials seemed to suggest ever-smokers with advanced mutated epidermal growth factor receptor (EGFRm) non-small cell lung cancer (NSCLC) did not seem to benefit from EGFR tyrosine kinase inhibitors (TKIs) as first-line treatment when compared with platinum-doublet chemotherapy as measured by progression-free survival (PFS).
METHODS
A literature-based meta-analysis of PFS outcomes as measured by log-transformed pooled hazard ratio (HR) was performed using a random-effect model. Pooled HRs for smoking status, age, gender, ethnicity, type of EGFR mutation, and EGFR TKI were obtained. Comparison of the pooled HR was performed by metaregression analysis.
RESULTS
Among the 1,649 EGFRm NSCLC patients analyzed from 7 prospective randomized trials (WJTOG3405, NEJ002, EURTAC, OPTIMAL, LUX Lung-3, LUX Lung-6, and ENSURE), 83.7% were Asians, and 30.0% were ever-smokers. An equal percentage of ever-smokers received doublet chemotherapy (30.2%) or EGFR TKI (30.0%). The pooled HR for PFS was 0.29 (95% confidence interval [CI]: 0.21-0.39) for never-smokers and 0.54 (95% CI: 0.38-0.76) for ever-smokers (p < .007 by metaregression). The pooled PFS HR for exon 19 deletion was 0.25 (95% CI: 0.19-0.31) and 0.44 for exon 21 substitution (95% CI: 0.34-0.57) (p < .001 by metaregression analysis). The pooled PFS HR was 0.33 (95% CI: 0.24-0.46) for Asians and 0.48 for non-Asians (95% CI: 0.28-0.84) (p = .261 by metaregression analysis).
CONCLUSION
EGFRm NSCLC patients derived significant PFS benefit from TKI over platinum-doublet chemotherapy as first-line treatment regardless of smoking status; however, PFS benefit is significantly better in never-smokers by metaregression analysis.
背景
多项随机III期试验的单因素分析似乎表明，与铂类双联化疗相比，晚期表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）既往吸烟者作为一线治疗使用EGFR酪氨酸激酶抑制剂（TKIs）时，无进展生存期（PFS）未显示出获益。
方法
采用随机效应模型，基于文献对以对数转换合并风险比（HR）衡量的PFS结果进行荟萃分析。获得吸烟状态、年龄、性别、种族、EGFR突变类型和EGFR TKI的合并HR。通过Meta回归分析对合并HR进行比较。
结果
在来自7项前瞻性随机试验（WJTOG3405、NEJ002、EURTAC、OPTIMAL、LUX Lung-3、LUX Lung-6和ENSURE）分析的1649例EGFR突变NSCLC患者中，83.7%为亚洲人，30.0%为既往吸烟者。接受双联化疗（30.2%）或EGFR TKI（30.0%）的既往吸烟者比例相同。从不吸烟者的PFS合并HR为0.29（95%置信区间[CI]：0.21 - 0.39），既往吸烟者为0.54（95% CI：0.38 - 0.76）（Meta回归分析p < 0.007）。外显子19缺失的PFS合并HR为0.25（95% CI：0.19 - 0.31），外显子21置换为0.44（95% CI：0.34 - 0.57）（Meta回归分析p < 0.001）。亚洲人的PFS合并HR为0.33（95% CI：0.24 - 0.46），非亚洲人为0.48（95% CI：0.28 - 0.84）（Meta回归分析p = 0.261）。
结论
EGFR突变的NSCLC患者作为一线治疗，无论吸烟状态如何，TKI治疗较铂类双联化疗均能显著延长PFS；然而，通过Meta回归分析，从不吸烟者的PFS获益显著更好。
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