Successful Treatment of Lung Adenocarcinoma with Epidermal Growth Factor Receptor Compound Mutations Involving Exon 19 Deletion and Exon 20 Insertion by Afatinib

TPS8123 Background: D is an orally available, potent and selective irreversible small molecule inhibitor of all catalytically active members of the HER (human epidermal growth factor receptor) family tyrosine kinases that has shown activity in preclinical studies on EGFR mutant cell lines, including those resistant to G. In a phase II trial of NSCLC pts who received 1st-line D, 75.6% of 45 pts with confirmed EGFR exon 19 or 21 sensitizing mutations (m) experienced a partial response (PR). The median progression-free survival (PFS) was 18.2 mo, and the PFS rate at 1 yr was 76.5% (preliminary data; Mok et al APLCC 2012). Methods: Based on the phase II data, a phase III randomized, open label trial (ARCHER 1050; NCT01774721) was designed to compare the efficacy of 1st line D with G in pts with adv EGFR m-positive NSCLC. Eligible pts (N=440) have pathologically confirmed stage IIIB/IV NSCLC with at least one activating EGFR m, either exon 19 deletion or exon 21 L858R m. Concurrent m in exon 20 T790M is permitted. Pts must have radiologically measurable disease, ECOG PS 0–1 and no prior systemic therapy. Pts will be randomized (1:1) to receive D 45 mg or G 250 mg orally once daily. The primary endpoint is PFS by Independent Radiologic Review. Secondary endpoints include PFS by investigator assessment, overall survival (OS), OS at 30 mo, best overall response, duration of response, and safety and tolerability. Pt-reported outcomes (HRQoL and disease/treatment-related symptoms) were also assessed. Randomization will be stratified by race (Japanese vs mainland Chinese vs other East Asian vs nonEEast Asian), and EGFR m status (exon 19 deletion vs exon 21 L858R m). A minimum of 268 PFS events is required for 90% power to detect a PFS improvement of ≥50% in D vs G recipients using the intent-to-treat (ITT) analysis population (HR ≤0.667). A significant (0.025 significance level) 1-sided stratified log-rank test for PFS at the final PFS analysis will be indicative of a positive study outcome. An interim analysis is planned to assess safety and whether early discontinuation of the trial is required for futility. Clinical trial information: NCT01774721.

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Successful treatment with weekly high-dose erlotinib against meningeal metastases from epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma

Respiratory Investigation ◽

10.1016/j.resinv.2016.04.001 ◽

2016 ◽

Vol 54 (5) ◽

pp. 372-375 ◽

Cited By ~ 3

Author(s):

Ryota Kanemaru ◽

Yoshiteru Morio ◽

Hidenori Takekawa ◽

Hitomi Jo ◽

Fumiko Kasuga ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Lung Adenocarcinoma ◽

Successful Treatment ◽

Growth Factor Receptor ◽

High Dose ◽

Epidermal Growth ◽

Egfr Mutated

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Epidermal Growth Factor Receptor ( EGFR ) Mutation in Exon 19 (p.E749Q) Confers Resistance to Gefitinib in One Patient With Lung Adenocarcinoma

Clinical Lung Cancer ◽

10.1016/j.cllc.2017.01.003 ◽

2017 ◽

Vol 18 (3) ◽

pp. e215-e217 ◽

Cited By ~ 2

Author(s):

Giovenzio Genestreti ◽

Dario de Biase ◽

Monica Di Battista ◽

Giovanna Cavallo ◽

Roberta Degli Esposti ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Epidermal Growth ◽

Exon 19

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Epidermal growth factor receptor variants in patients from Myanmar with lung adenocarcinoma

Asian Biomedicine ◽

10.1515/abm-2020-0011 ◽

2020 ◽

Vol 14 (2) ◽

pp. 75-81

Author(s):

Khine San Yin ◽

Myint Myint Naing ◽

Nitar Khine ◽

May Phyo Maung ◽

Aye Aye Nyunt ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Lung Adenocarcinoma ◽

Growth Factor Receptor ◽

Small Sample ◽

Fisher Exact Test ◽

Test Kit ◽

Epidermal Growth ◽

Exon 20

Abstract Background Epidermal growth factor receptor (EGFR) sequence variants in patients from Myanmar have not yet been reported. Objectives To describe the molecular epidemiology of EGFR variants in patients from Myanmar with lung adenocarcinoma. Methods Histological diagnosis and categorization of biopsies collected from 66 patients (28–78 years) with lung cancer was conducted using a panel of antibodies including those to: TTF1, P40, synaptophysin, CK7, and napsin-A. Samples from patients with confirmed adenocarcinoma were tested for EGFR variants using a cobas EGFR Mutation Test kit and cobas z 480 System (Roche). We conducted a univariate analysis of categorical factors using a χ2 or Fisher exact test. Results Histological types were adenocarcinoma (61%, 40/66), squamous cell carcinoma (24%, 16/66), neuroendocrine carcinoma (9%, 6/66), undifferentiated carcinoma (2%, 1/66), adenosquamous carcinoma (2%, 1/66), small cell anaplastic carcinoma (2%, 1/66), and pleomorphic sarcoma (2%, 1/66). EGFR variants were detected in 15 of 40 (38%) cases of adenocarcinoma. Among them, 6 patients (40%) had an exon 19 deletion, another 6 (40%) had exon 21 substitutions, 1 (7%) had exon 20 insertion S768I, and 2 (13%) had compound variations (1 of exon 21 L858R and exon 18 G719X, and 1 of exon 20 S768I and exon 18 G719X). Although limited by small sample size, no significant association was found between the variants and factors including family cancer history, age group, sex, ethnicity, or occupation. However, there was a strong significant association between never-smokers and EGFR variants (P = 0.008). Conclusion Knowledge of EGFR variants in patients from Myanmar is encouraging for their effective cancer treatment.

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