First-generation EGFR tyrosine kinase inhibitor therapy in 106 patients with compound EGFR-mutated lung cancer: a single institution's clinical practice experience.

Abstract

BACKGROUND:

The antitumour efficacy of tyrosine kinase inhibitors (TKIs) in lung cancer patients with compound epidermal growth factor receptor (EGFR) mutations has not been resolved. Our study summarizes a single institutional experience of first-generation TKI therapy for lung cancers with compound EGFR mutations.

METHODS:

A total of 106 consecutive patients with tumours bearing compound EGFR mutations were identified between January 2012 and May 2016; all patients received first-generation TKI therapy. Deletions in exon 19 and the L858R point mutation in exon 21 were considered common mutations; T790M was considered separately because of its association with TKIs resistances. Any other mutation was defined as a rare mutation. Patients were divided as follows: double common mutations (group A); common plus T790M mutations (group B); common plus rare mutations (group C); double rare mutations (group D); and rare plus T790M mutations (group E). A separate group of 115 consecutive patients with a single common mutation was created for comparative analysis (group F).

RESULTS:

The frequency of patients with compound EGFR was 2.9% (114/3925) and their response rate to first-generation TKIs was 50.9%, which was not significantly different from group F (67.0%, P = 0.088). The progression-free survival (PFS) of the 106 patients receiving TKI therapy was worse than that of group F (median, 9.1 vs. 13.0 months, respectively; P < 0.001). The PFS of the compound mutation group was shorter than that of the single common mutation group (median, 10.1 months in group A, P = 0.240; 9.1 months in group B, P < 0.001; 9.6 months in group C, P = 0.010; 6.5 months in group D, P = 0.048; 5.4 months in group E, P = 0.017). Patients with a co-occurring mutation in exon 20 (excluding T790M) exhibited significantly worse PFS than the patients with other compound mutations or with a single common mutation (median, 6.5 vs. 9.1 vs. 13.0 months, respectively, P = 0.002).

CONCLUSIONS:

There was significant heterogeneity among the compound EGFR mutations and their response to first-generation TKIs. Individualized treatment in clinical practice should be considered for each case.

• Authors: Xiangyang Yu, Xuewen Zhang, Zichen Zhang, Yongbin Lin, Yingsheng Wen, Yongqiang Chen, Weidong Wang, Lanjun Zhang
• Journal: Cancer communications (London, England) (Cancer Commun (Lond)) Vol. 38 Issue 1 Pg. 51 (07 28 2018) ISSN: 2523-3548 [Electronic] United States
• PMID: 30055651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Kinase Inhibitors
• EGFR protein, human
• ErbB Receptors

Topics

• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Disease-Free Survival
• Drug Resistance, Neoplasm (drug effects, genetics)
• ErbB Receptors (antagonists & inhibitors, genetics)
• Exons (genetics)
• Female
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Male
• Middle Aged
• Multivariate Analysis
• Mutation
• Protein Kinase Inhibitors (therapeutic use)
• Retrospective Studies
• Treatment Outcome