Prognostic and predictive value of carcinoembryonic antigen and cytokeratin-19 fragments levels in advanced non-small cell lung cancer patients treated with gefitinib or erlotinib

Abstract

Purpose: The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib.

Materials and methods: Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers.

Results: Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS.

Conclusion: h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma.

Fig. 1

Progression-free survival curves according to pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1). (A) CEA. (B) CYFRA 21-1. (C) Combinations of CEA and CYFRA 21-1 by group: a, patients with a low level of CEA and a high level of CYFRA 21-1; b, patients with both low or high level of CEA and CYFRA 21-1; and c, patients with a high level of CEA and a low level of CYFRA 21-1. PFS, progression-free survival.

Fig. 2

Progression-free survival curves according to pretreatment serum levels of combination of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) by histologic difference. a, Patients with a low level of CEA and a high level of CYFRA 21-1; b, patients with both low or high level of CEA and CYFRA 21-1; and c, patients with a high level of CEA and a low level of CYFRA 21-1 (A) patients with adenocarcinoma, (B) in patients with squamous cell carcinoma. PFS, progression-free survival.

Fig. 3

Progression-free survival curves according to pretreatment serum levels of combination of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) by epidermal growth factor receptor (EGFR) mutation status; a, patients with a low level of CEA and a high level of CYFRA 21-1; b, patients with both low or high level of CEA and CYFRA 21-1; and c, patients with a high level of CEA and a low level of CYFRA 21-1. (A) Patients with negative EGFR mutation, (B) in patients with positive EGFR mutation, (C) in patients with unknown EGFR mutation status. PFS, progression-free survival.

Fig. 4

Overall survival curves according to pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1). (A) CEA. (B) CYFRA 21-1. (C) Combinations of CEA and CYFRA 21-1 by group: a, patients with a low level of CEA and a high level of CYFRA 21-1; b, patients with both low or high level of CEA and CYFRA 21-1; and c, patients with a high level of CEA and a low level of CYFRA 21-1. OS, overall survival.