Lv Chao, Ma Yuanyuan, Feng Qin, Lu Fangliang, Chi Yongkun, Wu Nan, Fang Jian, Yang Yue
Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
J Thorac Dis. 2020 Oct;12(10):5324-5335. doi: 10.21037/jtd-20-1265.
Although neoadjuvant chemotherapy could improve survival outcome in resectable non-small cell lung cancer (NSCLC), the efficacy of neoadjuvant targeted therapy is still unclear.
We retrospectively reviewed clinical records of stage I-IIIA lung adenocarcinoma patients treated with neoadjuvant targeted therapy or chemotherapy prior to surgery. The collected data were compared between the two groups. Tumor samples were collected and analyzed by sequencing to explore the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms.
A total of 134 patients were enrolled; of these, 119 (88.8%) had clinical stage II-IIIA disease. Radiographic response rate was significantly higher with neoadjuvant targeted therapy than with chemotherapy among patients harboring EGFR mutation [objective response rate (ORR): 55.8% 32.6%; P=0.030]. EGFR exon 19 deletion achieved better tumor response than those with exon 21 L858R mutation (ORR: 70.0% 40.0%; P=0.057). Postoperative complications, operation time, drainage volume, and postoperative hospital length of stay were comparable between two groups. There was no difference on disease free survival (DFS) between patients receiving neoadjuvant targeted therapy and chemotherapy (P=0.871), but those who continued long-term adjuvant targeted therapy had significantly longer DFS than those only treated with adjuvant chemotherapy postoperatively (P=0.011). A series of potential molecular mechanisms of EGFR-TKI primary resistance were detected; these included BIM deletion polymorphisms, T790M mutation, and , , , or mutations. Patients who presented stable disease (SD) response after TKI therapy had significantly lower EGFR mutation abundance than PR response (P=0.032).
Neoadjuvant EGFR-TKI appears to be more effective than conventional chemotherapy for EGFR-mutant NSCLC patients. This study provides evidence that needs to be investigated further in randomized controlled trials (RCT).
尽管新辅助化疗可改善可切除非小细胞肺癌（NSCLC）的生存结局，但新辅助靶向治疗的疗效仍不明确。
我们回顾性分析了术前接受新辅助靶向治疗或化疗的I-IIIA期肺腺癌患者的临床记录。对两组收集的数据进行比较。收集肿瘤样本并通过测序分析，以探索表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKI）的耐药机制。
共纳入134例患者；其中119例（88.8%）为临床II-IIIA期疾病。在携带EGFR突变的患者中，新辅助靶向治疗的影像学缓解率显著高于化疗[客观缓解率（ORR）：55.8%对32.6%；P=0.030]。EGFR外显子19缺失的患者比外显子21 L858R突变的患者获得更好的肿瘤缓解（ORR：70.0%对40.0%；P=0.057）。两组术后并发症、手术时间、引流量和术后住院时间相当。接受新辅助靶向治疗和化疗的患者无病生存期（DFS）无差异（P=0.871），但继续长期辅助靶向治疗的患者DFS显著长于术后仅接受辅助化疗的患者（P=0.011）。检测到一系列EGFR-TKI原发性耐药的潜在分子机制；这些机制包括BIM缺失多态性、T790M突变以及、、或突变。TKI治疗后出现疾病稳定（SD）反应的患者EGFR突变丰度显著低于部分缓解（PR）反应的患者（P=0.032）。
对于EGFR突变的NSCLC患者，新辅助EGFR-TKI似乎比传统化疗更有效。本研究提供了证据，需要在随机对照试验（RCT）中进一步研究。
