Survival Benefit and Toxicity Profile of Adjuvant Icotinib for Patients With EGFR Mutation-Positive Non-Small Cell Lung Carcinoma

A Retrospective Study

Ziqing Zeng; Bo Yan; Yulong Chen; Lianmin Zhang; Jianquan Zhu; Fan Yang; Feng Wei; Terence Chi Chun Tam; Diego Kauffmann-Guerrero; Ross Andrew Soo; Xiubao Ren; Jian You


Transl Lung Cancer Res. 2020;9(6):2401-2410. 

In This Article


Study Design and Patients

Our study was a retrospective analysis of patients with EGFR mutation-positive NSCLC who underwent R0 (microscopically margin-negative) resection and received adjuvant icotinib at the Thoracic Oncology Department of the Tianjin Cancer Hospital between November 2011 and December 2017. ADx-ARMS EGFR Five Mutations Detection Kit (Amoy Diagnostics, Xiamen, China) was used to test EGFR mutations. All patients who received icotinib treatment and included in this study were patients who were EGFR-TKI benefit population (EGFR-sensitive mutation-positive). Patients with negative or resistant EGFR mutations (such as T790M mutation) were excluded. The inclusion criteria were: (I) age ≥18 years; (II) pathologically confirmed diagnosis of stage IB-IIIB NSCLC and R0 resection (the following risk factors were required for stage IB patients: vascular invasion, visceral pleura involvement, solid or micropapillary components in invasive adenocarcinoma ≥30%, or dissemination within the airway); (III) no previous history of chemotherapy, radiotherapy, or targeted therapy; (IV) icotinib was started within eight weeks postoperatively, and there were no signs of tumor recurrence before starting the adjuvant therapy; (V) adequate functions of the hematological system, liver, and kidney; (VI) Eastern Cooperative Oncology Group (ECOG) performance status of 0–1; and (VII) postoperative survival >3 months.

The exclusion criteria were: (I) history of any cancer other than NSCLC [except for cervical carcinoma in situ, cured basal cell carcinoma, or bladder epithelial tumors (including Ta and Tis)] within 5 years before the adjuvant therapy; (II) history of previous interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any clinically documented active interstitial lung disease, or idiopathic pulmonary fibrosis; (III) partially controlled eye inflammation or eye infection, or any condition that may cause the above-mentioned eye diseases; (IV) any unstable systemic disease, including active infection, uncontrolled hypertension, unstable angina, angina that has started within the last 3 months, congestive heart failure (New York Heart Association grade ≥II), myocardial infarction (within 6 months), severe arrhythmia, or liver, kidney or metabolic diseases requiring medications; (V) human immunodeficiency virus infection; (VI) pregnant or lactating women; or (VII) history of previous neurological or mental disorders, including epilepsy or dementia.

The demographic and clinical characteristics of all patients were extracted from their medical records. All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013). The Ethics Committee approved this study of the Tianjin Cancer Hospital (No. bc2019078). Adjuvant icotinib was used only after a comprehensive discussion between the patient and the physicians, and after tumor board discussion. The patients provided informed consent before receiving adjuvant icotinib.

Adjuvant Therapy

R0 resection was achieved for all patients. Patients received adjuvant icotinib (125 mg, tid, orally) (Betta Pharmaceuticals Co., Ltd., Zhejiang, China) for 2 years. The medication was withdrawn if there was disease recurrence or intolerable toxicities. Any other postoperative combined therapies were recorded.

Outcomes and Follow-up

Patients were followed routinely every 3 months. The outcomes included the 2-year DFS rate, 3-year OS rates, DFS, OS, and adverse events (AEs). Subgroup DFS and OS analyses were conducted with disease stages, preoperative carcinoembryonic antigen (CEA) levels, history of smoking, and EGFR mutation. DFS was defined as the time from surgery to disease recurrence or all-cause death, whichever occurred first. The OS was defined as the time from surgery to all-cause death. AEs were reported and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

Statistical Analysis

SPSS 22.0 (IBM, Armonk, NY, USA) was used for statistical analysis. Continuous variables are expressed as means ± standard deviation (SD). Categorical variables are expressed as frequency (percentage). Patient DFS and OS were plotted using the Kaplan-Meier curve and compared using the log-ranking test. P<0.05 was considered statistically significant. The minimal post-hoc power was defined as 60%.