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

Abstract and Introduction


Background: Adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are increasing considered for the tailored management of resectable non-small cell lung cancer (NSCLC). This study aimed to analyze the survival and toxicity profile of patients with EGFR mutation-positive NSCLC treated with adjuvant icotinib.

Methods: This was a single-center retrospective study of patients with EGFR mutation-positive NSCLC who underwent R0 (microscopically margin-negative) resection and received adjuvant icotinib between November 2011 and December 2017. The outcomes included 2-year disease-free survival (DFS) rate, 3-year overall survival (OS) rates, DFS, OS, and adverse events (AEs).

Results: A total of 86 patients receiving adjuvant icotinib were included. Their mean age was 59.7±10.0 years, and 26 (30.2%) patients were male. The 2-year DFS rate was 86.7%, and the 3-year OS rate was 95.3% with adjuvant icotinib. DFS (P=0.044) and OS (P=0.003) are better in stage I/II disease than in stage III disease. There seems no differences in DFS and OS between patients with low or high preoperative CEA levels (cutoff of 5 ng/mL), patients with exon 19 or 21 EGFR mutation or patients with or without smoking history. The most common AEs with adjuvant icotinib were rash (83.7%) and diarrhea (19.8%). One (1.2%) patient-reported grade ≥3 AEs. No treatment-related death occurred.

Conclusions: For patients with EGFR mutation-positive NSCLC, adjuvant icotinib might be associated with a promising survival benefit, with an acceptable toxicity profile.


Non-small cell lung cancer (NSCLC) accounts for 85–90% of all lung cancers.[1] In the United States, the annual incidence of NSCLC is 75 per 100,000 men and 53.5 per 100,000 women; mortality is 55.9 per 100,000 men and 36.3 per 100,000 women.[2] In China, the age-standardized incidence of NSCLC is 190.63 per 100,000 individuals, and the age-standardized mortality is 106.98 per 100,000 individuals.[3]

The management of early NSCLC requires a multidisciplinary approach[4] with complete surgical resection being the mainstay of treatment.[5–8] Whilst platinum based adjuvant chemotherapy improves overall survival (OS) in stage II–IIIA,[9–15] treatment related toxicities can affect the quality of life and long-term survival benefits are often minimal.[16–18]

More recently, the use of adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) such as gefitinib, erlotinib or osimertinib, was reported to improve progression free survival in resected NSCLC harboring mutations in EGFR exon 19 and 21, and its use is associated with easier administration and a more favorable toxicity profiles when compared to chemotherapy.[19–22] For example, the ADJUVANT/CTONG1104 trial showed for the first time EGFR-TKI adjuvant therapy resulted in a higher 3-year disease-free survival (DFS) rate compared with cisplatin-based adjuvant chemotherapy in patients with completely resected stage II–IIIA (N1-N2) EGFR mutation-positive NSCLC (39.6% vs. 32.5%; P=0.316).[23] However, a recent meta-analysis revealed a PFS benefit of gefitinib or erlotinib compared with chemotherapy in patients with EGFR mutation-positive, but there was no OS benefit.[24] A retrospective study showed that, compared with no EGFR-TKI treatment, adjuvant erlotinib or gefitinib can improve the 2-year DFS rate of patients with resected lung adenocarcinoma harboring EGFR exon 19 or 21 mutations (89% vs. 72%; P=0.06).[21] In September 2020, the latest results of ADAURA phase 3 trial of osimertinib vs. placebo after resection of non-squamous IB-IIIA NSCLC was reported.[20] The results showed that the 2-year DFS rate of osimertinib group were higher than that of the placebo control group (89% vs. 52%); and the DFS hazard ratio (HR) of the two groups was 0.20 (99.12% CI: 0.14–0.30; P<0.001).

For the treatment of advanced NSCLC in second-line setting and beyond icotinib was proven to similarly efficacious but safer than gefitinib.[25,26] The recent CONVINCE trial showed that icotinib could be used as a first-line agent for patients with EGFR-positive stage IIIB/IV NSCLC,[27] but there is currently insufficient data for its use in the adjuvant setting. A retrospective study of adjuvant icotinib revealed it has survival benefits in R0 NSCLC with EGFR mutations with acceptable toxicity,[28] but a trial of adjuvant icotinib + chemotherapy vs. chemotherapy showed no DFS benefit of adding icotinib to chemotherapy.[29] The exploration of such approach is important since adjuvant EGFR-TKIs are considered part of a new era for the tailored management of resectable NSCLC;[30] importantly since the benefits of adjuvant EGFR-TKIs may be variable among different patient subset, data are required to refine patient selection in order to maximize the clinical benefit of such approach.

The present study aimed to examine the survival and toxicity profile of patients with EGFR mutation-positive NSCLC treated with adjuvant icotinib. The previous data can provide comparation and reference for our research. Therefore, in view of the difficulty of collecting strictly matched cases, we designed this study without a comparative arm. The results could provide insights into the management of selected patients with NSCLC.

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