• DOI:10.1200/JCO.2012.45.0981
• Corpus ID: 383773

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.

@article{Katakami2013LUXLung4A,
  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.},
  author={N 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},
  journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
  year={2013},
  volume={31 27},
  pages={
          3335-41
        }
}

• N. Katakami, S. Atagi, +12 authors N. Yamamoto
• Published 20 September 2013
• Medicine, Biology
• Journal of clinical oncology : official journal of the American Society of Clinical Oncology

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 progression-free 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%). Treatment-related 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.