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。
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.