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
Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 2013 September 20, 31 (27): 3335-41

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.

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