NOTCH1 和 CREBBP 共突变对完全切除的 EGFR 突变 NSCLC 辅助治疗的益处产生负面影响：III 期 IMPACT 研究的转化研究。
NOTCH1 and CREBBP co-mutations negatively affect the benefit of adjuvant therapy in completely resected EGFR-mutated NSCLC: translational research of phase III IMPACT study.
发表日期：2023 Oct 21
作者：
Satoshi Ikeda, Masahiro Tsuboi, Kazuko Sakai, Toshihiro Misumi, Hiroaki Akamatsu, Hiroyasu Shoda, Noriaki Sakakura, Atsushi Nakamura, Yasuhisa Ohde, Hidetoshi Hayashi, Kyoichi Okishio, Morihito Okada, Ichiro Yoshino, Jiro Okami, Kazuhisa Takahashi, Norihiko Ikeda, Masayuki Tanahashi, Yuichi Tambo, Haruhiro Saito, Shinichi Toyooka, Hidetoshi Inokawa, Toyofumi Chen-Yoshikawa, Toshihide Yokoyama, Tatsuro Okamoto, Noriko Yanagitani, Masahide Oki, Makoto Takahama, Kenji Sawa, Hirohito Tada, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Kazuto Nishio
来源：
Molecular Oncology
摘要：
III 期 IMPACT 研究 (UMIN000044738) 在完全切除的表皮生长因子受体 (EGFR) 突变的非小细胞肺癌 (NSCLC) 中比较了辅助吉非替尼与顺铂加长春瑞滨 (cis/vin)。尽管未达到无病生存（DFS）的主要终点，但我们寻找吉非替尼辅助疗效的分子预测因子。在参加 IMPACT 研究的 234 名患者中，使用切除的肺癌标本对 202 名患者的 409 种癌症相关基因突变和肿瘤突变负荷进行了分析。常见的体细胞突变包括肿瘤蛋白p53（TP53；58.4%）、CUB和Sushi多结构域3（CSMD3；11.8%）和NOTCH1（9.9%）。多变量分析显示，NOTCH1 共突变是吉非替尼组总生存 (OS) 的显着不良预后因素，而 cAMP 反应元件结合蛋白 (CREBBP) 共突变是 cis/vin 组 DFS 和 OS 的显着不良预后因素。在NOTCH1共突变患者中，吉非替尼组的OS比cis/vin组短（风险比5.49，95% CI 1.07-28.00），且存在显着的交互作用（交互作用P=0.039）。在 CREBBP 共突变患者中，吉非替尼组的 DFS 比 cis/vin 组更长，且存在显着的交互作用（交互作用 P=0.058）。在完全切除的 EGFR 突变 NSCLC 中，NOTCH1 和 CREBBP 突变可能分别预测接受吉非替尼和 cis/vin 治疗的患者预后不良。本文受版权保护。版权所有。
The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Although the primary endpoint of disease free survival (DFS) was not met, we searched for molecular predictors of adjuvant gefitinib efficacy. Of 234 patients enrolled in the IMPACT study, 202 patients were analyzed for 409 cancer-related gene mutations and tumor mutation burden using resected lung cancer specimens. Frequent somatic mutations included tumor protein p53 (TP53; 58.4%), CUB and Sushi multiple domains 3 (CSMD3; 11.8%), and NOTCH1 (9.9%). Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival (OS) in the gefitinib group and cAMP response element binding protein (CREBBP) co-mutation for DFS and OS in the cis/vin group. In patients with NOTCH1 co-mutations, gefitinib group had a shorter OS than cis/vin group (Hazard ratio 5.49, 95% CI 1.07-28.00), with a significant interaction (P for interaction=0.039). In patients with CREBBP co-mutations, the gefitinib group had a longer DFS than the cis/vin group, with a significant interaction (P for interaction=0.058). In completely resected EGFR-mutated NSCLC, NOTCH1 and CREBBP mutations might predict poor outcome in patients treated with gefitinib and cis/vin, respectively.This article is protected by copyright. All rights reserved.