Prognostic value of EGFR 19-del and 21-L858R mutations in patients with non-small cell lung cancer

Abstract

Previous studies have demonstrated a significant difference in clinical characteristics between patients with non-small cell lung cancer (NSCLC) harboring exon 19 deletion (19-del) and an exon point mutation (21-L858R) in EGFR. The present retrospective study aimed to investigate the differential prognosis in patients with NSCLC harboring exon 19-del and 21-L858R mutations. The clinical and follow-up data of 137 patients treated at the Zhongnan Hospital of Wuhan University (Wuhan, Hubei, China) between August 2012 and August 2016, who were diagnosed with stage IIIB-IV NSCLC harboring either exon 19-del or 21-L858R mutations, were analyzed. The patients were divided into the first-line tyrosine kinase inhibitor (TKI), first-line chemotherapy and second-line TKI treatment groups. The median progression-free survival (PFS) time of patients harboring the exon 19-del mutation was significantly improved compared with that in patients harboring the 21-L858R mutation (11.3 vs. 8.8 months, respectively; P=0.017) following first-line TKI treatments. However, no significant difference in the median PFS time was observed between the exon 19-del and 21-L858R groups following the first-line chemotherapy or second-line TKI treatment. In patients with the exon 19-del, first-line TKI treatment achieved an increased objective response rate (ORR; 51.9 vs. 18.5%; P=0.004) and disease control rate (96.2 vs. 77.8%; P=0.030), and a longer PFS time (11.3 vs. 8.0 months; P=0.034) compared with that in the patients following first-line chemotherapy. First- and second-line TKI treatment achieved a similar PFS time (11.3 vs. 11.0 months, respectively; P=0.140). However, in patients with the 21-L858R mutation, the first-line TKI therapy and first-line chemotherapy groups exhibited a similar PFS time (8.8 vs. 3.5 months, respectively; P=0.063), while the second-line TKI treatment group exhibited a significantly longer PFS time compared with the first-line TKI treatment group (13.6 vs. 8.8 months, respectively; P=0.030). There was a differential sensitivity to treatment between patients harboring the exon 19-del and 21-L858R mutations. Therefore, chemotherapy may increase the sensitivity to TKIs in patients harboring the 21-L858R mutation.

Keywords: 21-L858R mutation; exon 19 deletion; non-small cell lung cancer; progression-free survival; tyrosine kinase inhibitors.

Figure 1.

mPFS of patients with the exon 19-del or 21-L858R mutation administered with different treatment types. (A) The mPFS times for patients harboring the 19-del and 21-L858R mutation were 11.3 and 8.8 months (P=0.017), respectively, following use of first-line TKIs. (B) The mPFS times for patients harboring the 19-del and 21-L858R mutation were 8.0 and 3.5 months (P=0.105), respectively, following first-line chemotherapy. (C) The mPFS times for patients harboring the 19-del and 21-L858R mutation were 11.0 and 13.6 months (P=0.090), respectively, following use of second-line TKIs. mPFS, median progression-free survival; TKIs, tyrosine kinase inhibitors.

Figure 2.

mPFS of patients treated with first-line TKIs versus first-line chemotherapy, and first-line versus second-line TKIs. (A) The mPFS times of patients treated with first-line TKIs and chemotherapy were 10.5 and 5.7 months (P=0.007), respectively. (B) In patients with the 19-del mutation, the mPFS times of patients treated with first-line TKIs and chemotherapy were 11.3 and 8.0 months (P=0.034), respectively. (C) In patients with the 21-L858R mutation, the PFS times of patients treated with first-line TKIs and chemotherapy were 8.8 and 3.5 months (P=0.063), respectively. mPFS, median progression-free survival; TKIs, tyrosine kinase inhibitors.

Figure 3.

mPFS of patients treated with first-line and second-line TKIs. (A) The mPFS times of patients treated with first and second-line TKIs were 10.5 and 13.0 months (P=0.965), respectively. (B) In patients with the 19-del mutation, the mPFS times of patients treated with first- and second-line TKIs were 11.3 and 11.0 months (P=0.140), respectively. (C) In patients with the 21-L858R mutation, the mPFS times of those treated with first- and second-line TKIs were 8.8 and 13.6 months (P=0.03), respectively. mPFS, median progression-free survival; TKIs, tyrosine kinase inhibitors.