Icotinib versus chemotherapy as adjuvant treatment for stage II–IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial,The Lancet Respiratory Medicine

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Icotinib versus chemotherapy as adjuvant treatment for stage II–IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial
The Lancet Respiratory Medicine ( IF 38.7 ) Pub Date : 2021-07-21 , DOI: 10.1016/s2213-2600(21)00134-x
Jianxing He ₁ , Chunxia Su ₂ , Wenhua Liang ₁ , Shidong Xu ₃ , Lin Wu ₄ , Xiangning Fu ₅ , Xiaodong Zhang ₆ , Di Ge ₇ , Qun Chen ₈ , Weimin Mao ₉ , Lin Xu ₁₀ , Chun Chen ₁₁ , Bing Hu ₁₂ , Guoguang Shao ₁₃ , Jian Hu ₁₄ , Jian Zhao ₁₅ , Xiaoqing Liu ₁₆ , Zhidong Liu ₁₇ , Zheng Wang ₁₈ , Zemin Xiao ₁₉ , Taiqian Gong ₂₀ , Wen Lin ₂₁ , Xingya Li ₂₂ , Feng Ye ₂₃ , Yang Liu ₂₄ , Haitao Ma ₂₅ , Yunchao Huang ₂₆ , Jianying Zhou ₂₇ , Zhonglin Wang ₂₈ , Junke Fu ₂₉ , Lieming Ding ₃₀ , Li Mao ₃₀ , Caicun Zhou ₂

Affiliation

Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Department of Thoracic Surgery and Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Thoracic Medicine Department II, Hunan Cancer Hospital, Changsha, China.
Thoracic Surgery Department, Tongji Hospital, Tongji Medical College of HUST, Wuhan, China.
Medical Oncology, Nantong Tumor Hospital, Nantong, China.
Thoracic Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, China.
Oncology Department, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, China.
Thoracic Surgery Department, Zhejiang Cancer Hospital, Hangzhou, China.
Thoracic Surgery Department, Jiangsu Cancer Hospital, Nanjing, China.
Thoracic Surgery Department, Fujian Medical University Union Hospital, Fuzhou, China.
Tumor- chemotherapy Department, Anhui Provincial Hospital, Hefei, China.
Thoracic Surgery Department, The First Hospital of Jilin University, Changchun, China.
Thoracic Surgery Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Thoracic Surgery Department, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
Department of Pulmonary Oncology, The 5th Medical Center of PLA General Hospital, Beijing, China.
Thoracic Surgery Department II, Beijing Chest Hospital, Capital Medical University, Beijing, China.
Thoracic Surgery Department, Shenzhen People's Hospital, Shenzhen, China.
Oncology Department, The First People's Hospital of Changde City, Changde, China.
Thoracic Surgery Department, The 6th Medical Center of PLA General Hospital, Beijing, China.
Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China.
Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
Thoracic Surgery Department, Chinese PLA General Hospital, Beijing, China.
Thoracic Surgery Department, The First Affiliated Hospital of Soochow University, Suzhou, China.
Thoracic Surgery Department I, Yunnan Cancer Hospital, Kunming, China.
Respiratory Medicine Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cardio-Thoracic Surgery, The First People's Hospital of Changzhou, Changzhou, China.
Thoracic Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Betta Pharmaceuticals, Hangzhou, China.

Background

Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study.

Methods

In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18–70 years, had histopathogically confirmed stage II–IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m² on days 1 and 8 of each cycle plus cisplatin 75 mg/m² on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m² plus cisplatin 75 mg/m² on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov, NCT02448797.

Findings

Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6–36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4–not reached) in the icotinib group and 22·1 months (16·8–30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24–0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8–73·7) in the icotinib group and 32·5% (21·3–44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42–1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group.

Interpretation

Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection.