LUX-lung 4: A phase ii trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both

Nobuyuki Katakami, Shinji Atagi, Koichi Goto, Toyoaki Hida, Takeshi Horai, Akira Inoue, Yukito Ichinose, Kunihiko Koboyashi, Koji Takeda, Katsuyuki Kiura, Kazuto Nishio, Yoko Seki, Ryuichi Ebisawa, Mehdi Shahidi, Nobuyuki Yamamoto

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

Purpose New molecular targeted agents are needed for patients with non-small-cell lung cancer (NSCLC) who progress while receiving erlotinib, gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant models with EGFR-activating mutations, including T790M. Patients and Methods This was a Japanese single-arm phase II trial conducted in patients with stage IIIB to IV pulmonary adenocarcinoma who progressed after -12 weeks of prior erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary end point was objective response rate (complete response or partial response) by independent review. Secondary end points included progressionfree survival (PFS), overall survival (OS), and safety. Results Of 62 treated patients, 45 (72.6%) were EGFR mutation positive in their primary tumor according to local and/or central laboratory analyses. Fifty-one patients (82.3%) fulfilled the criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable patients, five (8.2%; 95% CI, 2.7% to 18.1%) had a confirmed objective response rate (partial response). Median PFS was 4.4 months (95% CI, 2.8 to 4.6 months), and median OS was 19.0 months (95% CI, 14.9 months to not achieved). Two patients had acquired T790M mutations: L858R +T790M, and deletion in exon 19 T790M; they had stable disease for 9 months and 1 month, respectively. The most common afatinib-related adverse events (AEs) were diarrhea (100%) and rash/acne (91.9%). Treatmentrelated AEs leading to afatinib discontinuation were experienced by 18 patients (29%), of whom four also had progressive disease. Conclusion Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both.

Original languageEnglish
Pages (from-to)3335-3342
Number of pages8
JournalJournal of Clinical Oncology
Volume31
Issue number27
DOIs
Publication statusPublished - Sep 20 2013

Fingerprint

Non-Small Cell Lung Carcinoma
Lung
Therapeutics
Survival
Mutation
gefitinib
BIBW 2992
Erlotinib Hydrochloride
Acne Vulgaris
Proxy
Exanthema
Epidermal Growth Factor Receptor
Exons
Diarrhea
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

LUX-lung 4 : A phase ii trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. / Katakami, Nobuyuki; Atagi, Shinji; Goto, Koichi; Hida, Toyoaki; Horai, Takeshi; Inoue, Akira; Ichinose, Yukito; Koboyashi, Kunihiko; Takeda, Koji; Kiura, Katsuyuki; Nishio, Kazuto; Seki, Yoko; Ebisawa, Ryuichi; Shahidi, Mehdi; Yamamoto, Nobuyuki.

In: Journal of Clinical Oncology, Vol. 31, No. 27, 20.09.2013, p. 3335-3342.

Research output: Contribution to journalArticle

Katakami, N, Atagi, S, Goto, K, Hida, T, Horai, T, Inoue, A, Ichinose, Y, Koboyashi, K, Takeda, K, Kiura, K, Nishio, K, Seki, Y, Ebisawa, R, Shahidi, M & Yamamoto, N 2013, 'LUX-lung 4: A phase ii trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both', Journal of Clinical Oncology, vol. 31, no. 27, pp. 3335-3342. https://doi.org/10.1200/JCO.2012.45.0981
Katakami, Nobuyuki ; Atagi, Shinji ; Goto, Koichi ; Hida, Toyoaki ; Horai, Takeshi ; Inoue, Akira ; Ichinose, Yukito ; Koboyashi, Kunihiko ; Takeda, Koji ; Kiura, Katsuyuki ; Nishio, Kazuto ; Seki, Yoko ; Ebisawa, Ryuichi ; Shahidi, Mehdi ; Yamamoto, Nobuyuki. / LUX-lung 4 : A phase ii trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 27. pp. 3335-3342.
@article{9f0f801faefe4559a89ef570bc77992a,
title = "LUX-lung 4: A phase ii trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both",
abstract = "Purpose New molecular targeted agents are needed for patients with non-small-cell lung cancer (NSCLC) who progress while receiving erlotinib, gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant models with EGFR-activating mutations, including T790M. Patients and Methods This was a Japanese single-arm phase II trial conducted in patients with stage IIIB to IV pulmonary adenocarcinoma who progressed after -12 weeks of prior erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary end point was objective response rate (complete response or partial response) by independent review. Secondary end points included progressionfree survival (PFS), overall survival (OS), and safety. Results Of 62 treated patients, 45 (72.6{\%}) were EGFR mutation positive in their primary tumor according to local and/or central laboratory analyses. Fifty-one patients (82.3{\%}) fulfilled the criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable patients, five (8.2{\%}; 95{\%} CI, 2.7{\%} to 18.1{\%}) had a confirmed objective response rate (partial response). Median PFS was 4.4 months (95{\%} CI, 2.8 to 4.6 months), and median OS was 19.0 months (95{\%} CI, 14.9 months to not achieved). Two patients had acquired T790M mutations: L858R +T790M, and deletion in exon 19 T790M; they had stable disease for 9 months and 1 month, respectively. The most common afatinib-related adverse events (AEs) were diarrhea (100{\%}) and rash/acne (91.9{\%}). Treatmentrelated AEs leading to afatinib discontinuation were experienced by 18 patients (29{\%}), of whom four also had progressive disease. Conclusion Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both.",
author = "Nobuyuki Katakami and Shinji Atagi and Koichi Goto and Toyoaki Hida and Takeshi Horai and Akira Inoue and Yukito Ichinose and Kunihiko Koboyashi and Koji Takeda and Katsuyuki Kiura and Kazuto Nishio and Yoko Seki and Ryuichi Ebisawa and Mehdi Shahidi and Nobuyuki Yamamoto",
year = "2013",
month = "9",
day = "20",
doi = "10.1200/JCO.2012.45.0981",
language = "English",
volume = "31",
pages = "3335--3342",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "27",

}

TY - JOUR

T1 - LUX-lung 4

T2 - A phase ii trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both

AU - Katakami, Nobuyuki

AU - Atagi, Shinji

AU - Goto, Koichi

AU - Hida, Toyoaki

AU - Horai, Takeshi

AU - Inoue, Akira

AU - Ichinose, Yukito

AU - Koboyashi, Kunihiko

AU - Takeda, Koji

AU - Kiura, Katsuyuki

AU - Nishio, Kazuto

AU - Seki, Yoko

AU - Ebisawa, Ryuichi

AU - Shahidi, Mehdi

AU - Yamamoto, Nobuyuki

PY - 2013/9/20

Y1 - 2013/9/20

N2 - Purpose New molecular targeted agents are needed for patients with non-small-cell lung cancer (NSCLC) who progress while receiving erlotinib, gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant models with EGFR-activating mutations, including T790M. Patients and Methods This was a Japanese single-arm phase II trial conducted in patients with stage IIIB to IV pulmonary adenocarcinoma who progressed after -12 weeks of prior erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary end point was objective response rate (complete response or partial response) by independent review. Secondary end points included progressionfree survival (PFS), overall survival (OS), and safety. Results Of 62 treated patients, 45 (72.6%) were EGFR mutation positive in their primary tumor according to local and/or central laboratory analyses. Fifty-one patients (82.3%) fulfilled the criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable patients, five (8.2%; 95% CI, 2.7% to 18.1%) had a confirmed objective response rate (partial response). Median PFS was 4.4 months (95% CI, 2.8 to 4.6 months), and median OS was 19.0 months (95% CI, 14.9 months to not achieved). Two patients had acquired T790M mutations: L858R +T790M, and deletion in exon 19 T790M; they had stable disease for 9 months and 1 month, respectively. The most common afatinib-related adverse events (AEs) were diarrhea (100%) and rash/acne (91.9%). Treatmentrelated AEs leading to afatinib discontinuation were experienced by 18 patients (29%), of whom four also had progressive disease. Conclusion Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both.

AB - Purpose New molecular targeted agents are needed for patients with non-small-cell lung cancer (NSCLC) who progress while receiving erlotinib, gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant models with EGFR-activating mutations, including T790M. Patients and Methods This was a Japanese single-arm phase II trial conducted in patients with stage IIIB to IV pulmonary adenocarcinoma who progressed after -12 weeks of prior erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary end point was objective response rate (complete response or partial response) by independent review. Secondary end points included progressionfree survival (PFS), overall survival (OS), and safety. Results Of 62 treated patients, 45 (72.6%) were EGFR mutation positive in their primary tumor according to local and/or central laboratory analyses. Fifty-one patients (82.3%) fulfilled the criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable patients, five (8.2%; 95% CI, 2.7% to 18.1%) had a confirmed objective response rate (partial response). Median PFS was 4.4 months (95% CI, 2.8 to 4.6 months), and median OS was 19.0 months (95% CI, 14.9 months to not achieved). Two patients had acquired T790M mutations: L858R +T790M, and deletion in exon 19 T790M; they had stable disease for 9 months and 1 month, respectively. The most common afatinib-related adverse events (AEs) were diarrhea (100%) and rash/acne (91.9%). Treatmentrelated AEs leading to afatinib discontinuation were experienced by 18 patients (29%), of whom four also had progressive disease. Conclusion Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both.

UR - http://www.scopus.com/inward/record.url?scp=84884618137&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884618137&partnerID=8YFLogxK

U2 - 10.1200/JCO.2012.45.0981

DO - 10.1200/JCO.2012.45.0981

M3 - Article

C2 - 23816963

AN - SCOPUS:84884618137

VL - 31

SP - 3335

EP - 3342

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 27

ER -