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

Disclosures

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

In This Article

Results

Characteristics of the Patients

Table 1 presents the characteristics of the 86 patients receiving adjuvant icotinib. Their mean age was 59.7±10.0 years, and 26 (30.2%) patients were male. All patients had an ECOG performance status of 0. Most patients had lung adenocarcinoma [81 (94.2%)], T2 disease [69 (80.2%)], N0 disease [57 (66.3%)], preoperative CEA ≤5 ng/mL [63 (73.2%)], and underwent lobectomy [67 (77.9%)]. The EGFR mutations were: exon 18 (n=2, 2.3%), exon 19 (n=40, 46.5%), exon 20 (n=1, 1.2%), exon 21 (n=42, 48.8%), and compound exon 19 & 21 mutation (n=1, 1.2%). In addition to adjuvant icotinib, 5 (5.8%) and 13 (15.1%) patients received postoperative chemotherapy and radiotherapy, respectively.

Survival

The median follow-up time was 48 months. Most patients (93%) had a follow-up period of more than 3 years. Figure 1 presents the survival data of patients receiving adjuvant icotinib. The median DFS and OS were not reached. The 2-year DFS rate and the 3-year OS rate was 86.7% and 95.3%, respectively.

Figure 1.

Kaplan-Meier curves of patients receiving adjuvant icotinib. (A) Disease-free survival. (B) Overall survival.

Subgroup analysis

We excluded patients who had received combined postoperative therapy and performed a subgroup analysis. The results showed that DFS (P=0.044) and OS (P=0.003) is better in stage I/II disease than in stage III disease (Figure 2). Specifically, DFS (P=0.041) and OS (P=0.007) is better in T1–2 disease than in T3–4 disease. N0 disease had better DFS (P=0.016), and a better trend of OS (P=0.061) was found compared with N1–2 disease (Figure S1). 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 (Figure 2). However, as some subgroup numbers are small (especially after we excluded patients with combined treatment), we calculated the post-hoc power of all subgroup analyses, and the power is low (<60%). Thus, we cannot draw the conclusions that there is no difference in DFS or OS between those groups as this study are not powered to answer. However, all these statistical results in this study may provide some hints for future research, and these results need to be verified by future studies with larger sample sizes.

Figure 2.

Kaplan-Meier curves for the subgroup analyses in patients receiving adjuvant icotinib. Subgroup DFS (A) and OS (B) curves based on overall TNM stage (I/II vs. III); subgroup DFS (C) and OS (D) curves with preoperative carcinoembryonic antigen level (≤5 vs. >5 ng/mL); subgroup DFS (E) and OS (F) curves for epidermal growth factor receptor mutation (19 vs. 21); and subgroup DFS (G) and OS (H) curves for the history of smoking (yes vs. no). DFS, disease-free survival; OS, overall survival.

Figure S1.

Kaplan-Meier curves for the subgroup analyses in patients receiving adjuvant icotinib. Subgroup DFS (A) and OS (B) curves with T stage (T1/2 vs. T3/4); and subgroup DFS (C) and OS (D) curves with N stage (N0 vs. N1/2). DFS, disease-free survival; OS, overall survival.

AEs

AEs are shown in Table 2. Of the patients who received adjuvant icotinib, 73 (84.9%) had grade 1–2 AEs, and one (1.2%) had grade 3 AEs. Among them, 72 (83.7%) had a rash, 17 (19.8%) developed diarrhea, 4 (4.7%) had elevated transaminases, 5 (5.8%) experienced fatigue (including one grade 3 fatigue), 4 (4.7%) had oral ulcers, and 1 (1.2%) had nausea. Most AEs were relieved without any treatment. Patients without spontaneous relief were treated symptomatically, and no severe AEs, including interstitial lung disease, occurred. Multiple AEs were observed in 24 (32.9%) patients.

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