Erlotinib versus gefitinib for brain metastases in Asian patients with exon 19 EGFR-mutant lung adenocarcinoma: a retrospective, multicenter study

AbstractBackground. The brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.Patients and methods. We retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.Results. Out of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.Conclusions. Except for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.

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Acquired Resistance to EGFR Tyrosine Kinase Inhibitors is Associated With Low Efficacy of Radiation Therapy for Brain Metastases From EGFR-mutant Lung Adenocarcinoma

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2012.07.166 ◽

2012 ◽

Vol 84 (3) ◽

pp. S102

Author(s):

H. Hirata ◽

K. Nakamura ◽

N. Kunitake ◽

Y. Shioyama ◽

T. Sasaki ◽

...

Keyword(s):

Radiation Therapy ◽

Brain Metastases ◽

Tyrosine Kinase ◽

Lung Adenocarcinoma ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Acquired Resistance ◽

Egfr Tyrosine Kinase ◽

Egfr Tyrosine Kinase Inhibitors ◽

Egfr Mutant

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Faculty Opinions recommendation of Erlotinib versus radiation therapy for brain metastases in patients with EGFR-mutant lung adenocarcinoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718331006.793501269 ◽

2014 ◽

Author(s):

Minesh Mehta ◽

Manmeet Ahluwalia

Keyword(s):

Radiation Therapy ◽

Brain Metastases ◽

Lung Adenocarcinoma ◽

Egfr Mutant

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Co-mutation features in treatment-naïve EGFR-mutant lung adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21616 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21616-e21616

Author(s):

Jun Zhao ◽

Zaiwen Fan ◽

Donghong Chen ◽

Minglei Zhuo ◽

Zhen Liang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Chinese Patients ◽

Therapeutic Effects ◽

Significant Difference ◽

Treatment Naïve ◽

Exon 19 Deletion ◽

Egfr Mutant ◽

Egfr Tkis ◽

Exon 19

e21616 Background: In Chinese patients with lung adenocarcinoma, the positive rate of EGFR mutation was 40% - 50%, EGFR-TKIs therapy for lung cancer was also aimed at this part of patients. However, different EGFR mutation types have different therapeutic effects, this study focuses on different EGFR mutation types to divide the population of lung adenocarcinoma. Methods: We retrospectively reviewed gene test results of two hundred and sixty-two treatment-naïve adenocarcinoma patients. Tumor tissues (199, 76%), plasma (46, 17.5%) and other samples (17, 6.5%) were subject to next-generation sequencing using a 59-gene panel, which enables simultaneously assess SNV, Indel, rearrangements and CNV variations. Results: There were 174 females. These patients were divided into four groups, which 139 were EGFR L858R, 99 were EGFR exon 19 deletion, 7 were EGFR 20 ins and 17 were uncommon EGFR mutations, the co-mutation proportions with EGFR were 84.9% (118/139), 76.8% (76/99), 71.4% (5/7) and 94.1% (16/17) respectively. The mean numbers of co-mutation genes in L858R and exon 19 deletion were 4.173 and 3.258 (p<0.05). TP53 mutation was detected in 14.3% (1/7) 20ins group, which had a significant difference to L858R (59.7%, 83/139) and uncommon mutation groups (70.6%, 12/17) (p<0.05). Meanwhile, EGFR amplification proportion in L858R (18%, 25/139) and exon 19 deletion (6.1%, 6/99) were significantly different (p<0.05). The actionable mutations associated with target therapy involved in multiple pathways, for example, the HRR pathway and cell cycle pathway, related genes had no significant difference among the four groups. In these lung adenocarcinoma patients, we also found 6 EGFR T790M (2.3%, 6/262). Three cases accompanied with exon 19 deletion, and another three were L858R, no distribution in 20ins and uncommon groups. Conclusions: The phenomenon of concurrent gene mutation in treatment-naïve EGFR-mutant lung adenocarcinoma is common. EGFR mutant subgroups have different co-mutation features, like gene number and mutated genes. It may be the factor leading to different therapeutic effects of EGFR-TKIs, and indicate the importance of multiplex molecular test and further researches of target therapies.

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