Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non-small cell lung cancer except both exon 19 deletion and exon 21 L858R: a retrospective analysis in Korea.

Baek, Jin Ho; Sun, Jong-Mu; Min, Young Joo; Cho, Eun Kyung; Cho, Byoung Chul; Kim, Joo-Hang; Ahn, Myung-Ju; Park, Keunchil
Lung cancer (Amsterdam, Netherlands)
2015Feb ; 87 ( 2 ) :148-54.
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Baek, Jin Ho - Division of Oncology, Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Sun, Jong-Mu - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Min, Young Joo - Division of Oncology, Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea. Electronic address yjmin65@gmail.com.
Cho, Eun Kyung - Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.
Cho, Byoung Chul - Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea.
Kim, Joo-Hang - Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea.
Ahn, Myung-Ju - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Park, Keunchil - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
ABSTRACT
BACKGROUND: NSCLC can be defined by various molecular criteria, especially by the type of EGFR mutations present. Besides two major EGFR mutations, other rare or complex types have not been fully described. We performed this study to investigate the clinical significance and efficacy of EGFR-TKIs in NSCLC patients with rare or complex EGFR mutations.

METHODS: We retrospectively reviewed data for consecutive patients with advanced NSCLC. Subjects with wild type EGFR, EGFR del-19 alone, or EGFR L858R alone were excluded. A rare mutation was defined as any mutation other than del-19 or L858R in exon 21 and a complex mutation was defined as two or more different mutations co-existing within the same tumor sample.

RESULTS: A total of 1738 patients underwent EGFR genotyping. Among them, 88 (5.1%) had rare or complex mutations and 54 were treated with TKIs. Thirty-three patients had single rare mutations and 21 had complex mutations. The response was evaluated in 50 patients. Partial response was achieved in 11 (20.4%) patients, and stable disease was achieved in 20 (37.0%) patients. The median progression-free survival was 2.6 months (95% CI; 0.0-5.4 months) at a median follow-up duration of 381.0 days (range; 10-1307 days). The median overall survival was 12.7 months (95% CI; 7.2-18.2 months).

CONCLUSIONS: These results suggest that rare or complex EGFR mutations confer inferior response and survival to the EGFR-TKI treatment compared to common mutations. Further studies using larger numbers of patients are needed to determine better subclassifications for these patients. CI - Copyright ??2014 Elsevier Ireland Ltd. All rights reserved.
keyword
Clinical trials; EGFR; Morbidity; Mortality; NSCLC; Rare or complex mutations
MESH
Adult, Aged, Alleles, Antineoplastic Agents/*therapeutic use, Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/mortality/pathology, *Exons, Female, Genotype, Humans, Kaplan-Meier Estimate, Lung Neoplasms/*drug therapy/*genetics/mortality/pathology, Male, Middle Aged, *Mutation, Mutation Rate, Neoplasm Staging, Protein Kinase Inhibitors/*therapeutic use, Receptor, Epidermal Growth Factor/*genetics, Republic of Korea, Retreatment, Retrospective Studies, Sequence Deletion, Treatment Outcome
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DOI
10.1016/j.lungcan.2014.11.013.
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