Osimertinib for Japanese patients with T790M-positive advanced non-small-cell lung cancer: A pooled subgroup analysis

Tomonori Hirashima, Miyako Satouchi, Toyoaki Hida, Makoto Nishio, Terufumi Kato, Hiroshi Sakai, Fumio Imamura, Katsuyuki Kiura, Isamu Okamoto, Kazuo Kasahara, Hirohiko Uchida, Sarah L. Vowler, Tetsuya Mitsudomi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard of care for non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations. However, almost all patients develop resistance after approximately 1 y of treatment, with >50% of cases due to the T790M secondary mutation of the EGFR gene. A large global Phase III study (AURA3) demonstrated that osimertinib significantly prolonged progression-free survival (PFS) over platinum-doublet chemotherapy in patients with T790M-positive NSCLC who had progressed on previous EGFR-TKI therapy. However, it is not clear whether efficacy or safety of osimertinib in Japanese patients is similar to the overall population. We report a pre-planned subgroup analysis of pooled Phase II data from the AURA Extension and AURA2 trials to investigate the efficacy and safety of osimertinib in Japanese patients. This study included 81 Japanese patients. Patients were administered 80 mg osimertinib orally once daily until disease progression. The main endpoints were objective response rate (ORR), PFS, and safety. The ORR was 63.6% and median PFS was 13.8 mo. Overall survival rate at 36 mo was 54.0%. The most common all-cause adverse events (AEs) were rash (grouped term; 65.4%), diarrhea (51.9%), paronychia (grouped term; 49.4%), and dry skin (grouped term; 39.5%). Most AEs were grade 1-2. Five patients (6.2%) developed interstitial lung disease, resulting in two deaths (2.5%). Osimertinib demonstrated favorable ORR and PFS in Japanese patients, similar to the overall population. Additionally, osimertinib has good efficacy and a manageable safety profile in Japanese patients with NSCLC who had acquired resistance due to the T790M mutation.

Original languageEnglish
JournalCancer Science
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Non-Small Cell Lung Carcinoma
Disease-Free Survival
Epidermal Growth Factor Receptor
Safety
Protein-Tyrosine Kinases
Mutation
Paronychia
osimertinib
erbB-1 Genes
Interstitial Lung Diseases
Standard of Care
Exanthema
Platinum
Population
Disease Progression
Diarrhea
Survival Rate
Drug Therapy
Skin
Therapeutics

Keywords

  • acquired resistance
  • EGFR mutation
  • non-small-cell lung cancer
  • osimertinib
  • tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Osimertinib for Japanese patients with T790M-positive advanced non-small-cell lung cancer : A pooled subgroup analysis. / Hirashima, Tomonori; Satouchi, Miyako; Hida, Toyoaki; Nishio, Makoto; Kato, Terufumi; Sakai, Hiroshi; Imamura, Fumio; Kiura, Katsuyuki; Okamoto, Isamu; Kasahara, Kazuo; Uchida, Hirohiko; Vowler, Sarah L.; Mitsudomi, Tetsuya.

In: Cancer Science, 01.01.2019.

Research output: Contribution to journalArticle

Hirashima, T, Satouchi, M, Hida, T, Nishio, M, Kato, T, Sakai, H, Imamura, F, Kiura, K, Okamoto, I, Kasahara, K, Uchida, H, Vowler, SL & Mitsudomi, T 2019, 'Osimertinib for Japanese patients with T790M-positive advanced non-small-cell lung cancer: A pooled subgroup analysis', Cancer Science. https://doi.org/10.1111/cas.14120
Hirashima, Tomonori ; Satouchi, Miyako ; Hida, Toyoaki ; Nishio, Makoto ; Kato, Terufumi ; Sakai, Hiroshi ; Imamura, Fumio ; Kiura, Katsuyuki ; Okamoto, Isamu ; Kasahara, Kazuo ; Uchida, Hirohiko ; Vowler, Sarah L. ; Mitsudomi, Tetsuya. / Osimertinib for Japanese patients with T790M-positive advanced non-small-cell lung cancer : A pooled subgroup analysis. In: Cancer Science. 2019.
@article{08f3e5ed20904bbb9ddaada90c03890f,
title = "Osimertinib for Japanese patients with T790M-positive advanced non-small-cell lung cancer: A pooled subgroup analysis",
abstract = "Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard of care for non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations. However, almost all patients develop resistance after approximately 1 y of treatment, with >50{\%} of cases due to the T790M secondary mutation of the EGFR gene. A large global Phase III study (AURA3) demonstrated that osimertinib significantly prolonged progression-free survival (PFS) over platinum-doublet chemotherapy in patients with T790M-positive NSCLC who had progressed on previous EGFR-TKI therapy. However, it is not clear whether efficacy or safety of osimertinib in Japanese patients is similar to the overall population. We report a pre-planned subgroup analysis of pooled Phase II data from the AURA Extension and AURA2 trials to investigate the efficacy and safety of osimertinib in Japanese patients. This study included 81 Japanese patients. Patients were administered 80 mg osimertinib orally once daily until disease progression. The main endpoints were objective response rate (ORR), PFS, and safety. The ORR was 63.6{\%} and median PFS was 13.8 mo. Overall survival rate at 36 mo was 54.0{\%}. The most common all-cause adverse events (AEs) were rash (grouped term; 65.4{\%}), diarrhea (51.9{\%}), paronychia (grouped term; 49.4{\%}), and dry skin (grouped term; 39.5{\%}). Most AEs were grade 1-2. Five patients (6.2{\%}) developed interstitial lung disease, resulting in two deaths (2.5{\%}). Osimertinib demonstrated favorable ORR and PFS in Japanese patients, similar to the overall population. Additionally, osimertinib has good efficacy and a manageable safety profile in Japanese patients with NSCLC who had acquired resistance due to the T790M mutation.",
keywords = "acquired resistance, EGFR mutation, non-small-cell lung cancer, osimertinib, tyrosine kinase inhibitor",
author = "Tomonori Hirashima and Miyako Satouchi and Toyoaki Hida and Makoto Nishio and Terufumi Kato and Hiroshi Sakai and Fumio Imamura and Katsuyuki Kiura and Isamu Okamoto and Kazuo Kasahara and Hirohiko Uchida and Vowler, {Sarah L.} and Tetsuya Mitsudomi",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/cas.14120",
language = "English",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Osimertinib for Japanese patients with T790M-positive advanced non-small-cell lung cancer

T2 - A pooled subgroup analysis

AU - Hirashima, Tomonori

AU - Satouchi, Miyako

AU - Hida, Toyoaki

AU - Nishio, Makoto

AU - Kato, Terufumi

AU - Sakai, Hiroshi

AU - Imamura, Fumio

AU - Kiura, Katsuyuki

AU - Okamoto, Isamu

AU - Kasahara, Kazuo

AU - Uchida, Hirohiko

AU - Vowler, Sarah L.

AU - Mitsudomi, Tetsuya

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard of care for non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations. However, almost all patients develop resistance after approximately 1 y of treatment, with >50% of cases due to the T790M secondary mutation of the EGFR gene. A large global Phase III study (AURA3) demonstrated that osimertinib significantly prolonged progression-free survival (PFS) over platinum-doublet chemotherapy in patients with T790M-positive NSCLC who had progressed on previous EGFR-TKI therapy. However, it is not clear whether efficacy or safety of osimertinib in Japanese patients is similar to the overall population. We report a pre-planned subgroup analysis of pooled Phase II data from the AURA Extension and AURA2 trials to investigate the efficacy and safety of osimertinib in Japanese patients. This study included 81 Japanese patients. Patients were administered 80 mg osimertinib orally once daily until disease progression. The main endpoints were objective response rate (ORR), PFS, and safety. The ORR was 63.6% and median PFS was 13.8 mo. Overall survival rate at 36 mo was 54.0%. The most common all-cause adverse events (AEs) were rash (grouped term; 65.4%), diarrhea (51.9%), paronychia (grouped term; 49.4%), and dry skin (grouped term; 39.5%). Most AEs were grade 1-2. Five patients (6.2%) developed interstitial lung disease, resulting in two deaths (2.5%). Osimertinib demonstrated favorable ORR and PFS in Japanese patients, similar to the overall population. Additionally, osimertinib has good efficacy and a manageable safety profile in Japanese patients with NSCLC who had acquired resistance due to the T790M mutation.

AB - Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the standard of care for non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations. However, almost all patients develop resistance after approximately 1 y of treatment, with >50% of cases due to the T790M secondary mutation of the EGFR gene. A large global Phase III study (AURA3) demonstrated that osimertinib significantly prolonged progression-free survival (PFS) over platinum-doublet chemotherapy in patients with T790M-positive NSCLC who had progressed on previous EGFR-TKI therapy. However, it is not clear whether efficacy or safety of osimertinib in Japanese patients is similar to the overall population. We report a pre-planned subgroup analysis of pooled Phase II data from the AURA Extension and AURA2 trials to investigate the efficacy and safety of osimertinib in Japanese patients. This study included 81 Japanese patients. Patients were administered 80 mg osimertinib orally once daily until disease progression. The main endpoints were objective response rate (ORR), PFS, and safety. The ORR was 63.6% and median PFS was 13.8 mo. Overall survival rate at 36 mo was 54.0%. The most common all-cause adverse events (AEs) were rash (grouped term; 65.4%), diarrhea (51.9%), paronychia (grouped term; 49.4%), and dry skin (grouped term; 39.5%). Most AEs were grade 1-2. Five patients (6.2%) developed interstitial lung disease, resulting in two deaths (2.5%). Osimertinib demonstrated favorable ORR and PFS in Japanese patients, similar to the overall population. Additionally, osimertinib has good efficacy and a manageable safety profile in Japanese patients with NSCLC who had acquired resistance due to the T790M mutation.

KW - acquired resistance

KW - EGFR mutation

KW - non-small-cell lung cancer

KW - osimertinib

KW - tyrosine kinase inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85070085114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070085114&partnerID=8YFLogxK

U2 - 10.1111/cas.14120

DO - 10.1111/cas.14120

M3 - Article

C2 - 31265163

AN - SCOPUS:85070085114

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

ER -