背景：表皮生長因子受體(EGFR)-酪氨酸激酶抑製劑是對 EGFR 突變陽性、未經治療的轉移性非小細胞肺癌(NSCLC)的標準護理。然而 2011 年本研究開始時，吉非替尼對具有 EGFR突變的肺癌輔助化療的療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，隨機分配 234 例 24 個月 EGFR 突變陽性（外顯子19 缺失或 1858R）、II-III 期 NSCLC 接受吉非替尼（250mg，每日 1 次）或順鉑（第 1 天）每 3 周加長春瑞濱（第 1 天為 25mg/m2）（cis/vin，以下用此代稱），共 4 個周期。根據意向治療(ITT)人群的中心綜述，主要終點是無病生存率(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.

結果：吉非替尼組的 2 例患者撤回同意，被排除在 ITT 人群之外。吉非替尼組未見治療相關死亡，但 cis/vin 組有 3 例治療相關死亡。隨訪的中位持續時間為 71 個月。吉非替尼組的中位數 DFS（36 個月）比 cis/vin 組的中位數 DFS 長（25.2 個月）。然而卡普蘭-邁耶曲線在手術後 5 年左右開始重疊，DFS 無顯著差異，風險比為 0.92（95%置信區間(CI)，0.67-1.28；P=0.63）。總體生存率也無顯著差異（兩臂均未達到中值）。吉非替尼和 cis/vin 組的五年生存率分別為 78.0%和 74.6%，風險比為 1.03, 95%置信區間為 0.65-1.65，P=0.89。探索性子群分析顯示，吉非替尼組（n=19/27，G 至 cis/vin）患者比 cis/vin 組存活時間長（HR=0.31；95%置信區間為 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).

結論：輔助吉非替尼似乎可預防早期複發，但在完全切除 II-III 期、EGFR 突變 NSCLC患者中未顯著延長 DFS 或 OS。DFS/OS 的明顯的非劣效性可能證明在選定的患者中使用輔助吉非替尼，特別是那些被認為不適合 cis/vin 輔助治療的患者。

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.