Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer

AURA3 trial

Hiroaki Akamatsu, Nobuyuki Katakami, Isamu Okamoto, Terufumi Kato, Young Hak Kim, Fumio Imamura, Masaharu Shinkai, Rachel A. Hodge, Hirohiko Uchida, Toyoaki Hida

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small-cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase III study comparing the efficacy of osimertinib (80 mg/d) with platinum-based therapy plus pemetrexed (500 mg/m2) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary end-point was progression-free survival (PFS) based on investigator assessment. Improvement in PFS was clinically meaningful in the osimertinib group (n = 41) vs the platinum-pemetrexed group (n = 22; hazard ratio 0.27; 95% confidence interval, 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in 5 patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR T790M mutation-positive NSCLC whose disease has progressed following first-line EGFR-TKI treatment. (ClinicalTrials.gov trial registration no. NCT02151981.).

Original languageEnglish
Pages (from-to)1930-1938
Number of pages9
JournalCancer Science
Volume109
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Pemetrexed
Mutation
Protein-Tyrosine Kinases
Platinum
Disease-Free Survival
Therapeutics
Safety
osimertinib
Phosphotransferases
Research Personnel
Confidence Intervals
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer : AURA3 trial. / Akamatsu, Hiroaki; Katakami, Nobuyuki; Okamoto, Isamu; Kato, Terufumi; Kim, Young Hak; Imamura, Fumio; Shinkai, Masaharu; Hodge, Rachel A.; Uchida, Hirohiko; Hida, Toyoaki.

In: Cancer Science, Vol. 109, No. 6, 01.06.2018, p. 1930-1938.

Research output: Contribution to journalArticle

Akamatsu, H, Katakami, N, Okamoto, I, Kato, T, Kim, YH, Imamura, F, Shinkai, M, Hodge, RA, Uchida, H & Hida, T 2018, 'Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial', Cancer Science, vol. 109, no. 6, pp. 1930-1938. https://doi.org/10.1111/cas.13623
Akamatsu, Hiroaki ; Katakami, Nobuyuki ; Okamoto, Isamu ; Kato, Terufumi ; Kim, Young Hak ; Imamura, Fumio ; Shinkai, Masaharu ; Hodge, Rachel A. ; Uchida, Hirohiko ; Hida, Toyoaki. / Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer : AURA3 trial. In: Cancer Science. 2018 ; Vol. 109, No. 6. pp. 1930-1938.
@article{fbf06421d0a84b0dad79fd677d27f5da,
title = "Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial",
abstract = "Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small-cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase III study comparing the efficacy of osimertinib (80 mg/d) with platinum-based therapy plus pemetrexed (500 mg/m2) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary end-point was progression-free survival (PFS) based on investigator assessment. Improvement in PFS was clinically meaningful in the osimertinib group (n = 41) vs the platinum-pemetrexed group (n = 22; hazard ratio 0.27; 95{\%} confidence interval, 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in 5 patients (12.2{\%}) treated with osimertinib and 12 patients (54.5{\%}) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR T790M mutation-positive NSCLC whose disease has progressed following first-line EGFR-TKI treatment. (ClinicalTrials.gov trial registration no. NCT02151981.).",
author = "Hiroaki Akamatsu and Nobuyuki Katakami and Isamu Okamoto and Terufumi Kato and Kim, {Young Hak} and Fumio Imamura and Masaharu Shinkai and Hodge, {Rachel A.} and Hirohiko Uchida and Toyoaki Hida",
year = "2018",
month = "6",
day = "1",
doi = "10.1111/cas.13623",
language = "English",
volume = "109",
pages = "1930--1938",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer

T2 - AURA3 trial

AU - Akamatsu, Hiroaki

AU - Katakami, Nobuyuki

AU - Okamoto, Isamu

AU - Kato, Terufumi

AU - Kim, Young Hak

AU - Imamura, Fumio

AU - Shinkai, Masaharu

AU - Hodge, Rachel A.

AU - Uchida, Hirohiko

AU - Hida, Toyoaki

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small-cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase III study comparing the efficacy of osimertinib (80 mg/d) with platinum-based therapy plus pemetrexed (500 mg/m2) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary end-point was progression-free survival (PFS) based on investigator assessment. Improvement in PFS was clinically meaningful in the osimertinib group (n = 41) vs the platinum-pemetrexed group (n = 22; hazard ratio 0.27; 95% confidence interval, 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in 5 patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR T790M mutation-positive NSCLC whose disease has progressed following first-line EGFR-TKI treatment. (ClinicalTrials.gov trial registration no. NCT02151981.).

AB - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small-cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase III study comparing the efficacy of osimertinib (80 mg/d) with platinum-based therapy plus pemetrexed (500 mg/m2) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary end-point was progression-free survival (PFS) based on investigator assessment. Improvement in PFS was clinically meaningful in the osimertinib group (n = 41) vs the platinum-pemetrexed group (n = 22; hazard ratio 0.27; 95% confidence interval, 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in 5 patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR T790M mutation-positive NSCLC whose disease has progressed following first-line EGFR-TKI treatment. (ClinicalTrials.gov trial registration no. NCT02151981.).

UR - http://www.scopus.com/inward/record.url?scp=85047811202&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047811202&partnerID=8YFLogxK

U2 - 10.1111/cas.13623

DO - 10.1111/cas.13623

M3 - Article

VL - 109

SP - 1930

EP - 1938

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 6

ER -