肿瘤

日本杉田学习院医院完全切除、EGFR 突变的 II-III 期非小细胞肺癌患者(影响,WJOG6410L):一项随机 3 期试验

作者:会飞的大胖纸 来源:医学论坛网 日期:2021-06-30
导读

         背景:表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂是对 EGFR 突变阳性、未经治疗的转移性非小细胞肺癌(NSCLC)的标准护理。然而 2011 年本研究开始时,吉非替尼对具有 EGFR突变的肺癌辅助化疗的疗效和安全性尚不清楚。 Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor is a

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背景:表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂是对 EGFR 突变阳性、未经治疗的转移性非小细胞肺癌(NSCLC)的标准护理。然而 2011 年本研究开始时,吉非替尼对具有 EGFR突变的肺癌辅助化疗的疗效和安全性尚不清楚。

 

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor is a standard of care for EGFR mutation-positive, untreated metastatic non-small cell lung cancer (NSCLC). However, the efficacy and safety of adjuvant gefitinib for patients with completely resected lung cancer harboring EGFR mutation over cisplatin-based adjuvant chemotherapy were not known in 2011 when this study was initiated.

 

方法:2011 年 9 月至 2015 年 12 月,随机分配 234 例 24 个月 EGFR 突变阳性(外显子19  缺失或 1858R)、II-III 期 NSCLC 接受吉非替尼(250mg,每日 1 次)或顺铂(第 1 天)每 3 周加长春瑞滨(第 1 天为 25mg/m2)(cis/vin,以下用此代称),共 4 个周期。根据意向治疗(ITT)人群的中心综述,主要终点是无病生存率(DFS)。

 

Methods: From September 2011 to December 2015, we randomly assigned 234 patients with completely resected, EGFR mutation-positive (exon 19 deletion or L858R), stage II–III NSCLC to receive either gefitinib (250 mg, once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8) (cis/vin) every 3 weeks for four cycles. The primary endpoint was disease-free survival (DFS) according to a central review in the intent-to-treat (ITT) population.

 

结果:吉非替尼组的 2 例患者撤回同意,被排除在 ITT 人群之外。吉非替尼组未见治疗相关死亡,但 cis/vin 组有 3 例治疗相关死亡。随访的中位持续时间为 71 个月。吉非替尼组的中位数 DFS(36 个月)比 cis/vin 组的中位数 DFS 长(25.2 个月)。然而卡普兰-迈耶曲线在手术后 5 年左右开始重叠,DFS 无显著差异,风险比为 0.92(95%置信区间(CI),0.67-1.28;P=0.63)。总体生存率也无显著差异(两臂均未达到中值)。吉非替尼和 cis/vin 组的五年生存率分别为 78.0%和 74.6%,风险比为 1.03, 95%置信区间为 0.65-1.65,P=0.89。探索性子群分析显示,吉非替尼组(n=19/27,G 至 cis/vin)患者比 cis/vin 组存活时间长(HR=0.31;95%置信区间为 0.10-0.98;P=0.046)。

 

Results: Two patients in the gefitinib arm withdrew consent and were excluded from the ITT population. No treatment-related deaths were seen in the gefitinib arm, but three treatment-related deaths were reported in the cis/vin arm. Median duration of follow-up was 71 months. Median DFS was numerically longer in the gefitinib arm (36 months) than in the cis/vin arm (25.2 months). However, Kaplan-Meier curves began to overlap around 5 years after surgery, and no significant difference in DFS was seen, with a hazard ratio (HR) of 0.92 (95% confidence interval (CI), 0.67–1.28; P = 0.63). Overall survival was also not significantly different (median not reached in either arm). Five-year survival rates for gefitinib and cis/vin arms were 78.0% and 74.6%, respectively, with an HR for death of 1.03; 95%CI, 0.65–1.65; P = 0.89. Exploratory subset analysis revealed that patients ³70 years old in the gefitinib arm (n = 19/27 with G to cis/vin) survived longer than those in the cis/vin arm (HR 0.31; 95%CI, 0.10–0.98; P = 0.046).

 

结论:辅助吉非替尼似乎可预防早期复发,但在完全切除 II-III 期、EGFR 突变 NSCLC患者中未显著延长 DFS 或 OS。DFS/OS 的明显的非劣效性可能证明在选定的患者中使用辅助吉非替尼,特别是那些被认为不适合 cis/vin 辅助治疗的患者。

 

Conclusions: Adjuvant gefitinib appeared to prevent early relapse, but did not significantly prolong DFS or OS in patients with completely resected stage II–III, EGFR-mutated NSCLC. The apparent non-inferiority of DFS/OS may justify the use of adjuvant gefitinib in selected subset of patients, especially those deemed unsuitable for cis/vin adjuvant therapy.

 

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