ADJUVANT（CTONG1104）研究是一项III期、前瞻性试验，旨在探索吉非替尼与标准联合化疗相比在EGFR敏感突变完全切除术后II-IIIa(N1-N2)非小细胞肺癌的疗效。

从2011年9月至2014年4月，共计27家医疗中心的222例患者入组，符合入组标准的患者接受术后辅助吉非替尼(250mg，口服，每日一次，共计2年治疗)或4周期长春瑞滨联合卡铂的标准治疗，主要研究终点为DFS，次要研究终点为OS，3年和5年DFS率，5年OS率。

结果：全体人群的中位随访时间为76.9个月，中位OS为75.5个月，42.8%的患者死亡。吉非替尼组和化疗组的OS分别为75.5个月和79.2个月，差异无统计学意义(HR=0.96, 95%CI 0.64-1.43, P=0.823)，3年OS率分别为68.6%和67.5%，5年OS率分别为53.8%和52.4%，3年DFS率分别为40.3%和33.2%，5年DFS率分别为23.4%和23.7%，差异均无统计学意义。所有预设的亚组分析，包括年龄、性别、淋巴结状态及EGFR突变类型差异均无统计学意义。接受后线靶向治疗的患者OS为75.5个月，优于接受其他治疗的36.4个月，差异有统计学意义。

研究提示，对于术后有淋巴结转移的EGFR突变患者，吉非替尼与标准联合化疗相比延长了DFS，但未延长OS。

这与晚期的一线EGFR-TKI研究的结果是相似的，提示只要能够使用EGFR-TKI治疗，最终OS相近，差异主要表现在DFS/PFS。

9005 Oral Abstract Session, Fri, 8:00 AM-11:00 AM

CTONG1104: Adjuvant gefitinib versus chemotherapy for resected N1-N2 NSCLC with EGFR mutation—Final overall survival analysis of the randomized phase III trial 1 analysis of the randomized phase III trial. 

First Author: Yi-Long Wu, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China

Background: ADJUVANT-CTONG1104, a randomized phase 3 trial showed adjuvant gefitinib treatment significantly improved disease-free survival (DFS) vs standard doublet chemotherapy in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). 5-year survival rate of N1N2 were 38%-50% in IASLC staging system. Here, we present the final overall survival (OS) results fromthe study. 

Methods: From Sep 2011 to April 2014, 222 patients, aged 18-75 years, with EGFR activating mutation through completely resection and diagnosed as stage II-IIIA (N1-N2) NSCLC pathologically from 27 sites were enrolled. The enrolled patients were 1:1 randomized to receive adjuvant gefitinib (250 mg once per day) for 24 months (G, n=111) or vinorelbine (25 mg/m2, d1 and d8) plus cisplatin (75 mg/m2, d1) every 3 weeks for 4 cycles (C, n=111). The primary endpoint was DFS in the ITT population. Secondary endpoints included OS, 3 and 5-year DFS rate, 5-year OS rate. The subsequent therapy data were collected, including crossover from C to G, rechallenge TKI and other treatment. Data cut-off date was Jan. 13, 2020.

Results: A median follow-up was 76.9 months. The median OS (mOS) was 75.5 months based on 95 (42.8%) events in ITT whole population. The mOS was 75.5min G arm and 79.2min C arm (HR 0.96, 95%CI 0.64-1.43, p=0.823). The 3, 5-year OS rate were 68.6%, 53.8% in G and 67.5%, 52.4% in C respectively. DFS in 3, 5-y were 40.3%, 23.4% in G and 33.2%, 23.7% in C, respectively (P3-y=0.395, P5-y=891). All predefined subgroups including age, gender, lymph node, EGFR mutation type had no significant difference in statistics but in favor of G arm in trend. Subsequent treatment especially targeted therapy contributed most to OS (HR = 0.46, 95% CI 0.26 – 0.83). Median OS of patients receiving subsequent target therapy was75.5m (n=35), 36.4m in other treatment (n=33; (P,0.001). For G mOS were 75.5 (n=15; target therapy) and 35.0 (n=18; other, p,0.001), for C 62.8m (n=20) and 46.8m (n=15; p=0.251). The RR was 26.7%, DCR 66.7%, mPFS 14.1mand mOS 19.6m for patients with rechallenged EGFR TKI in G arm (n=15).No novel unexpected SAE was observed during follow up. 

Conclusion The DFS survival advantage did not translate to OS difference in ADJUVANT trial. The OS with 75.5m was the best one of survival in completely resected N1N2 NSCLC comparing with historical data and sequent TKI treatment contribute to overall survival. 

Clinical trial information: NCT01405079. 

ASCO 2020摘要 

Cancer Prevention, Risk Reduction, and Genetics

Developmental Therapeutics—Immunotherapy

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Lung Cancer— Other Thoracic Cancers

Lung Cancer—Non-Small Cell Metastatic

Symptoms and Survivorship