Shen Leilei, Guo Juntang, Zhang Weidong, Zhang Lianbin, Liu Xi, Wang Tao, Zhang Tao, Liang Chaoyang, Liu Yang
Postgraduate School, Medical School of Chinese PLA, Beijing, People's Republic of China.
Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China.
Cancer Med. 2023 Sep;12(18):18470-18478. doi: 10.1002/cam4.6443. Epub 2023 Aug 9.
Adjuvant therapy for stage IB non-small cell lung cancer remains debatable. In this real-world study, we evaluate the efficacy and safety of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for resected stage IB lung adenocarcinoma.
This real-world study recruited 249 patients diagnosed with stage IB disease after surgical resection between January 2013 and September 2021. Sixty-six (26.5%) patients received adjuvant targeted therapy (TKIs group), and 183 (73.5%) were enrolled in the clinical observation (CO) group. Propensity scores were matched to minimize the observed confounder effects between the two groups, and 59 patient pairs were matched. The primary endpoint was disease-free survival (DFS).
In the TKI group, 38 (64.4%) patients chose to receive icotinib, 27.1% (16/59) received gefitinib, and 5 patients (8.5%) chose osimertinib. The median follow-up time was 30.8 months (range: 7-107 months). Two (3.4%) patients in the TKI group and 10 (16.9%) in the CO group experienced disease relapse. The 3-year DFS rates were 98.3% in the TKI group and 83.0% in the CO group (HR: 0.10; 95% CI: 0.01-0.78; p = 0.008). DFS differences were found in the entire cohort (p = 0.005) and the matched cohort (p = 0.024) between the two groups. Multivariate analysis showed that adjuvant EGFR-TKIs was an independent factor for DFS (HR: 0.211; 95% CI: 0.045-0.979; p = 0.047), along with poor cell differentiation (HR: 5.256; 95% CI: 1.648-16.769; p = 0.005), and spread through air spaces (HR: 5.612; 95% CI: 1.137-27.700; p = 0.034). None of the patients discontinued EGFR-TKIs owing to the low occurrence rate of treatment-related serious adverse events.
Adjuvant EGFR-TKIs could significantly improve DFS among patients with stage IB lung adenocarcinoma compared with CO, with a safe and tolerable profile.
IB期非小细胞肺癌的辅助治疗仍存在争议。在这项真实世界研究中，我们评估了辅助性表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）用于切除后的IB期肺腺癌的疗效和安全性。
这项真实世界研究纳入了2013年1月至2021年9月间手术切除后诊断为IB期疾病的249例患者。66例（26.5%）患者接受辅助靶向治疗（TKIs组），183例（73.5%）纳入临床观察（CO）组。进行倾向评分匹配以尽量减少两组间观察到的混杂因素影响，匹配了59对患者。主要终点为无病生存期（DFS）。
在TKIs组中，38例（64.4%）患者选择接受埃克替尼，27.1%（16/59）接受吉非替尼，5例（8.5%）选择奥希替尼。中位随访时间为30.8个月（范围：7 - 107个月）。TKIs组有2例（3.4%）患者出现疾病复发，CO组有10例（16.9%）。TKIs组的3年DFS率为98.3%，CO组为83.0%（HR：0.10；95%CI：0.01 - 0.78；p = 0.008）。两组在整个队列（p = 0.005）和匹配队列（p = 0.024）中均发现DFS存在差异。多因素分析显示，辅助性EGFR-TKIs是DFS的独立因素（HR：0.211；95%CI：0.045 - 0.979；p = 0.047），同时细胞分化差（HR：5.256；95%CI：1.648 - 16.769；p = 0.005）以及气腔播散（HR：5.612；95%CI：1.137 - 27.700；p = 0.034）也是独立因素。由于治疗相关严重不良事件发生率低，无患者停用EGFR-TKIs。
与临床观察相比，辅助性EGFR-TKIs可显著改善IB期肺腺癌患者的DFS，且安全性和耐受性良好。
