Lu Fangliang, Lv Chao, Yang Xin, Zhuo Minglei, Wang Jia, Xiong Hongchao, Chen Jinfeng, Yan Shi, Wang Yuzhao, Zhang Shanyuan, Wu Nan
Department of Thoracic Surgery II, Beijing Cancer Hospital, Beijing, China.
Department of Pathology, Beijing Cancer Hospital, Beijing, China.
Lung Cancer. 2025 Aug;206:108676. doi: 10.1016/j.lungcan.2025.108676. Epub 2025 Jul 19.
EGFR tyrosine kinase inhibitors (EGFR-TKIs) have shown activity in the neoadjuvant setting of EGFR-mutant (EGFRm) non-small cell lung cancer; however, data on the combination of neoadjuvant EGFR-TKIs plus chemotherapy are limited. This study aimed to evaluate the safety and efficacy of neoadjuvant icotinib plus chemotherapy for stage II-IIIB EGFRm lung adenocarcinoma.
NEOIPOWER is a single-arm, phase II study (NCT05104788). Eligible adult patients with resectable, stage II-IIIB, EGFRm lung adenocarcinoma received 8 weeks of 125 mg icotinib three times daily plus two 21-day cycles of chemotherapy (pemetrexed 500 mg/m and carboplatin AUC5 on day 1), followed by surgical resection. The primary endpoint was major pathologic response (MPR) rate. Secondary endpoints were R0 resection rate, objective response rate (ORR), pathologic complete response (pCR), disease control rate (DCR), disease-free survival (DFS), overall survival, and safety.
From October 25, 2021, to April 2, 2023, 30 patients were enrolled and completed neoadjuvant therapy. MPR was observed in 6.7 % of patients (95% CI, 0.8-22.1%), which did not meet the primary endpoint. No patients had pCR. Twenty-eight (93.3 %) patients underwent surgery, of whom 27 (96.4 %) achieved R0 resection, and pathological downstaging was observed in 10 (35.7 %) patients. The ORR was 83.3 % (95% CI, 65.3-94.4 %) and DCR was 96.7 % (95% CI, 82.8-99.9 %) among 30 treated patients. With a median follow-up of 25.0 (range, 6.4-33.6) months, the median DFS was not reached (95% CI, 25.1-not estimable), and the 2-year DFS rate was 92.0 %. Grade 3 treatment-related adverse events (TRAEs) were reported in 6 (20.0 %) patients and mainly included leukopenia (6.7 %) and neutropenia (6.7 %). No grade 4 or 5 TRAEs were observed, and no deaths occurred.
Neoadjuvant icotinib combined with chemotherapy did not meet its primary endpoint for MPR rate in resectable stage II-IIIB EGFRm lung adenocarcinoma, but demonstrated a manageable safety profile.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）在表皮生长因子受体突变（EGFRm）的非小细胞肺癌新辅助治疗中已显示出活性；然而，关于新辅助EGFR-TKIs联合化疗的数据有限。本研究旨在评估新辅助埃克替尼联合化疗治疗II-IIIB期EGFRm肺腺癌的安全性和疗效。
NEOIPOWER是一项单臂II期研究（NCT05104788）。符合条件的可切除II-IIIB期EGFRm肺腺癌成年患者接受为期8周的埃克替尼治疗，每日3次，每次125mg，联合两个21天周期的化疗（培美曲塞500mg/m²，卡铂AUC5，第1天给药），随后进行手术切除。主要终点是主要病理缓解（MPR）率。次要终点包括R0切除率、客观缓解率（ORR）、病理完全缓解（pCR）、疾病控制率（DCR）、无病生存期（DFS）、总生存期和安全性。
从2021年10月25日至2023年4月2日，30例患者入组并完成新辅助治疗。6.7%的患者观察到MPR（95%CI，0.8-22.1%），未达到主要终点。无患者达到pCR。28例（93.3%）患者接受了手术，其中27例（96.4%）实现R0切除，10例（35.7%）患者观察到病理降期。30例接受治疗的患者中，ORR为83.3%（95%CI，65.3-94.4%），DCR为96.7%（95%CI，82.8-99.9%）。中位随访25.0（范围6.4-33.6）个月，中位DFS未达到（95%CI，25.1-不可估计），2年DFS率为92.0%。6例（20.0%）患者报告了3级治疗相关不良事件（TRAEs），主要包括白细胞减少（6.7%）和中性粒细胞减少（6.7%）。未观察到4级或5级TRAEs，也未发生死亡。
新辅助埃克替尼联合化疗在可切除的II-IIIB期EGFRm肺腺癌中未达到MPR率的主要终点，但显示出可控的安全性。
