吉非替尼或厄洛替尼与化疗治疗 EGFR 突变阳性肺癌：总生存的个体患者数据分析荟萃分析。

Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival.

机构信息

NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia.

Cancer Care Centre, St. George Hospital, Sydney, Australia.

出版信息

J Natl Cancer Inst. 2017 Jun 1;109(6). doi: 10.1093/jnci/djw279.

DOI:10.1093/jnci/djw279

PMID:28376144

Abstract

BACKGROUND

We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).

METHODS

Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided.

RESULTS

Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P = .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0.79 to 1.16, P = .68) and L858R (n = 540, HR = 1.06, 95% CI = 0.86 to 1.32, P = .59) subgroups ( P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95% CI = 0.32 to 0.42, P < .001) and in all subgroups. Following progression, 73.8% from the chemotherapy arm received EGFR-TKI, and 65.9% from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6% from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95% CI = 11.4 to 14.3, vs 19.8 months, 95% CI = 17.6 to 21.7).

CONCLUSIONS

Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.

摘要

背景

我们进行了一项个体患者数据荟萃分析，以研究第一代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗对晚期非小细胞肺癌（NSCLC）总生存期（OS）的影响。

方法

使用比较 EGFR-TKI 与化疗治疗外显子 19 缺失（del19）或外显子 21 L858R（L858R）EGFR 突变患者的试验数据。我们进行 Cox 回归以获得风险比（HR）和 95%置信区间（CI）。在探索性分析中检查了进展后治疗的影响。所有统计检验均为双侧。

结果

六项符合条件的试验（吉非替尼=3，厄洛替尼=3）纳入了 1231 名患者；632 名接受 EGFR-TKI 治疗，599 名接受化疗。在中位 35.0 个月的随访中，有 780 人死亡，1004 人进展。EGFR-TKI 与化疗之间的 OS 无差异（HR=1.01，95%CI=0.88 至 1.17，P=0.84）。Del19（n=682，HR=0.96，95%CI=0.79 至 1.16，P=0.68）和 L858R（n=540，HR=1.06，95%CI=0.86 至 1.32，P=0.59）亚组（P 交互=0.47），或根据吸烟状态、性别、表现状态、年龄、种族或组织学，OS 也没有差异（P 交互=0.47）。然而，EGFR-TKI 总体上显著延长了无进展生存期（PFS）（HR=0.37，95%CI=0.32 至 0.42，P<0.001）和所有亚组的 PFS。进展后，化疗组 73.8%的患者接受了 EGFR-TKI，EGFR-TKI 组 65.9%的患者接受了化疗。EGFR-TKI 组有 9%的患者未接受进一步治疗，而化疗组有 0.6%的患者未接受进一步治疗。疾病进展后，随机分配至 EGFR-TKI 的患者的 OS 短于随机分配至化疗的患者（12.8 个月，95%CI=11.4 至 14.3，vs 19.8 个月，95%CI=17.6 至 21.7）。