Interstitial lung disease associated with gefitinib in Japanese patients with EGFR-mutated non-small-cell lung cancer: Combined analysis of two phase III trials (NEJ 002 and WJTOG 3405)

Hiroaki Akamatsu, Akira Inoue, Tetsuya Mitsudomi, Kunihiko Kobayashi, Kazuhiko Nakagawa, Keita Mori, Toshihiro Nukiwa, Yoichi Nakanishi, Nobuyuki Yamamoto

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective: Interstitial lung disease associated with gefitinib is a critical adverse reaction. When geftinib was administered to EGFR-unknown patients, the interstitial lung disease incidence rate was approximately 3-4% in Japan, and usually occurs during the first 4 weeks of treatment. However, it has not been fully investigated in EGFR-mutated patients. Methods: We collected clinical records of participants of two Phase III trials (WJTOG 3405 and NEJ 002), which compared gefitinib with platinum doublet chemotherapy. All patients were EGFR mutated, chemo-naïve and had good performance status. Results: A total of 402 patients were enrolled in this study. In the gefitinib arm, 10 (5.0%) of 201 patients developed interstitial lung disease, of whom five (2.5%) were Grade 3 or greater, with two deaths (1.0%). In contrast, only one patient developed interstitial lung disease (Grade 1) in the chemotherapy arm. With regard to gefitinib, smoking history was significantly associated with developing interstitial lung disease (odds ratio 0.18; 95% confidence interval: 0.05-0.74; P 1/4 0.01). The cumulative incidence rate of interstitial lung disease was similar in the 0-4, 5-8 and 9-12 week time periods. However, between smokers and never-smokers, cumulative incidence rates in the first 4 weeks were significantly different (4.7% versus 0%, P 1/4 0.03). Three of 10 patients developed interstitial lung disease after 8 weeks of gefitinib administration (days 135, 171 and 190, respectively). Conclusions: Among EGFR-mutated patients, the incidence of interstitial lung disease associated with gefitinib was not different from that in previous reports. Smoking history was associated with developing interstitial lung disease, and smokers had a higher incidence rate of interstitial lung disease in the first 4 weeks.

Original languageEnglish
Article numberhyt049
Pages (from-to)664-668
Number of pages5
JournalJapanese journal of clinical oncology
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 1 2013

Fingerprint

Interstitial Lung Diseases
Non-Small Cell Lung Carcinoma
Incidence
Smoking
History
gefitinib
Drug Therapy
Platinum
Japan
Odds Ratio
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Interstitial lung disease associated with gefitinib in Japanese patients with EGFR-mutated non-small-cell lung cancer : Combined analysis of two phase III trials (NEJ 002 and WJTOG 3405). / Akamatsu, Hiroaki; Inoue, Akira; Mitsudomi, Tetsuya; Kobayashi, Kunihiko; Nakagawa, Kazuhiko; Mori, Keita; Nukiwa, Toshihiro; Nakanishi, Yoichi; Yamamoto, Nobuyuki.

In: Japanese journal of clinical oncology, Vol. 43, No. 6, hyt049, 01.06.2013, p. 664-668.

Research output: Contribution to journalArticle

Akamatsu, Hiroaki ; Inoue, Akira ; Mitsudomi, Tetsuya ; Kobayashi, Kunihiko ; Nakagawa, Kazuhiko ; Mori, Keita ; Nukiwa, Toshihiro ; Nakanishi, Yoichi ; Yamamoto, Nobuyuki. / Interstitial lung disease associated with gefitinib in Japanese patients with EGFR-mutated non-small-cell lung cancer : Combined analysis of two phase III trials (NEJ 002 and WJTOG 3405). In: Japanese journal of clinical oncology. 2013 ; Vol. 43, No. 6. pp. 664-668.
@article{18662674f50f481a8b6ffb55477c93a7,
title = "Interstitial lung disease associated with gefitinib in Japanese patients with EGFR-mutated non-small-cell lung cancer: Combined analysis of two phase III trials (NEJ 002 and WJTOG 3405)",
abstract = "Objective: Interstitial lung disease associated with gefitinib is a critical adverse reaction. When geftinib was administered to EGFR-unknown patients, the interstitial lung disease incidence rate was approximately 3-4{\%} in Japan, and usually occurs during the first 4 weeks of treatment. However, it has not been fully investigated in EGFR-mutated patients. Methods: We collected clinical records of participants of two Phase III trials (WJTOG 3405 and NEJ 002), which compared gefitinib with platinum doublet chemotherapy. All patients were EGFR mutated, chemo-na{\"i}ve and had good performance status. Results: A total of 402 patients were enrolled in this study. In the gefitinib arm, 10 (5.0{\%}) of 201 patients developed interstitial lung disease, of whom five (2.5{\%}) were Grade 3 or greater, with two deaths (1.0{\%}). In contrast, only one patient developed interstitial lung disease (Grade 1) in the chemotherapy arm. With regard to gefitinib, smoking history was significantly associated with developing interstitial lung disease (odds ratio 0.18; 95{\%} confidence interval: 0.05-0.74; P 1/4 0.01). The cumulative incidence rate of interstitial lung disease was similar in the 0-4, 5-8 and 9-12 week time periods. However, between smokers and never-smokers, cumulative incidence rates in the first 4 weeks were significantly different (4.7{\%} versus 0{\%}, P 1/4 0.03). Three of 10 patients developed interstitial lung disease after 8 weeks of gefitinib administration (days 135, 171 and 190, respectively). Conclusions: Among EGFR-mutated patients, the incidence of interstitial lung disease associated with gefitinib was not different from that in previous reports. Smoking history was associated with developing interstitial lung disease, and smokers had a higher incidence rate of interstitial lung disease in the first 4 weeks.",
author = "Hiroaki Akamatsu and Akira Inoue and Tetsuya Mitsudomi and Kunihiko Kobayashi and Kazuhiko Nakagawa and Keita Mori and Toshihiro Nukiwa and Yoichi Nakanishi and Nobuyuki Yamamoto",
year = "2013",
month = "6",
day = "1",
doi = "10.1093/jjco/hyt049",
language = "English",
volume = "43",
pages = "664--668",
journal = "Japanese Journal of Clinical Oncology",
issn = "0368-2811",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Interstitial lung disease associated with gefitinib in Japanese patients with EGFR-mutated non-small-cell lung cancer

T2 - Combined analysis of two phase III trials (NEJ 002 and WJTOG 3405)

AU - Akamatsu, Hiroaki

AU - Inoue, Akira

AU - Mitsudomi, Tetsuya

AU - Kobayashi, Kunihiko

AU - Nakagawa, Kazuhiko

AU - Mori, Keita

AU - Nukiwa, Toshihiro

AU - Nakanishi, Yoichi

AU - Yamamoto, Nobuyuki

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Objective: Interstitial lung disease associated with gefitinib is a critical adverse reaction. When geftinib was administered to EGFR-unknown patients, the interstitial lung disease incidence rate was approximately 3-4% in Japan, and usually occurs during the first 4 weeks of treatment. However, it has not been fully investigated in EGFR-mutated patients. Methods: We collected clinical records of participants of two Phase III trials (WJTOG 3405 and NEJ 002), which compared gefitinib with platinum doublet chemotherapy. All patients were EGFR mutated, chemo-naïve and had good performance status. Results: A total of 402 patients were enrolled in this study. In the gefitinib arm, 10 (5.0%) of 201 patients developed interstitial lung disease, of whom five (2.5%) were Grade 3 or greater, with two deaths (1.0%). In contrast, only one patient developed interstitial lung disease (Grade 1) in the chemotherapy arm. With regard to gefitinib, smoking history was significantly associated with developing interstitial lung disease (odds ratio 0.18; 95% confidence interval: 0.05-0.74; P 1/4 0.01). The cumulative incidence rate of interstitial lung disease was similar in the 0-4, 5-8 and 9-12 week time periods. However, between smokers and never-smokers, cumulative incidence rates in the first 4 weeks were significantly different (4.7% versus 0%, P 1/4 0.03). Three of 10 patients developed interstitial lung disease after 8 weeks of gefitinib administration (days 135, 171 and 190, respectively). Conclusions: Among EGFR-mutated patients, the incidence of interstitial lung disease associated with gefitinib was not different from that in previous reports. Smoking history was associated with developing interstitial lung disease, and smokers had a higher incidence rate of interstitial lung disease in the first 4 weeks.

AB - Objective: Interstitial lung disease associated with gefitinib is a critical adverse reaction. When geftinib was administered to EGFR-unknown patients, the interstitial lung disease incidence rate was approximately 3-4% in Japan, and usually occurs during the first 4 weeks of treatment. However, it has not been fully investigated in EGFR-mutated patients. Methods: We collected clinical records of participants of two Phase III trials (WJTOG 3405 and NEJ 002), which compared gefitinib with platinum doublet chemotherapy. All patients were EGFR mutated, chemo-naïve and had good performance status. Results: A total of 402 patients were enrolled in this study. In the gefitinib arm, 10 (5.0%) of 201 patients developed interstitial lung disease, of whom five (2.5%) were Grade 3 or greater, with two deaths (1.0%). In contrast, only one patient developed interstitial lung disease (Grade 1) in the chemotherapy arm. With regard to gefitinib, smoking history was significantly associated with developing interstitial lung disease (odds ratio 0.18; 95% confidence interval: 0.05-0.74; P 1/4 0.01). The cumulative incidence rate of interstitial lung disease was similar in the 0-4, 5-8 and 9-12 week time periods. However, between smokers and never-smokers, cumulative incidence rates in the first 4 weeks were significantly different (4.7% versus 0%, P 1/4 0.03). Three of 10 patients developed interstitial lung disease after 8 weeks of gefitinib administration (days 135, 171 and 190, respectively). Conclusions: Among EGFR-mutated patients, the incidence of interstitial lung disease associated with gefitinib was not different from that in previous reports. Smoking history was associated with developing interstitial lung disease, and smokers had a higher incidence rate of interstitial lung disease in the first 4 weeks.

UR - http://www.scopus.com/inward/record.url?scp=84878663933&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878663933&partnerID=8YFLogxK

U2 - 10.1093/jjco/hyt049

DO - 10.1093/jjco/hyt049

M3 - Article

C2 - 23585689

AN - SCOPUS:84878663933

VL - 43

SP - 664

EP - 668

JO - Japanese Journal of Clinical Oncology

JF - Japanese Journal of Clinical Oncology

SN - 0368-2811

IS - 6

M1 - hyt049

ER -