Pneumologie 2016; 70 - P490
DOI: 10.1055/s-0036-1572233

Influence of dose adjustment on afatinib safety and efficacy in patients (pts) with advanced EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC)

N Dickgreber 1, JCH Yang 2, MJ Ahn 3, B Halmos 4, V Hirsh 5, M Hochmair 6, B Levy 7, F de Marinis 8, T Mok 9, K O'Byrne 10, I Okamoto 11, M Schuler 12, M Sebastian 13, R Shah 14, EH Tan 15, N Yamamoto 16, A Märten 17, D Massey 18, S Wind 19, D Carbone 20
  • 1Thoracic Oncology and Respiratory Care Medicine, Mathias Spital Rheine
  • 2National Taiwan University Hospital and National Taiwan University, Taipei
  • 3Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea
  • 4Columbia University Medical Center, New York
  • 5Mcgill University, Montreal, Canada
  • 6Otto Wagner Hospital, Vienna
  • 7Mount Sinai Beth Israel Hospital, New York
  • 8Division of Thoracic Oncology, European Institute of Oncology, Milan
  • 9State Key Laboratory of South China, Hong Kong Cancer Institute, The Chinese University of Hong Kong
  • 10Princess Alexandra Hospital and Queensland University of Technology, Brisbane
  • 11Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka
  • 12West German Cancer Center, University Hospital Essen, University Duisburg-Essen
  • 13Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, and University Medical Center of the Johannes Gutenberg University Mainz
  • 14Kent Oncology Centre, Maidstone Hospital, Kent
  • 15National Cancer Centre, Singapore
  • 16Wakayama Medical University, Wakayama
  • 17Boehringer Ingelheim Pharma GmbH & Co. Kg, Ingelheim am Rhein
  • 18Boehringer Ingelheim Ltd UK, Bracknell, Berkshire
  • 19Boehringer Ingelheim Pharma GmbH & Co. Kg, Biberach
  • 20James Thoracic Center, The Ohio State University Wexner Medical Center, Columbus

Background: Afatinib 40 mg/day (oral) is approved for the treatment of pts with advanced EGFRm+ NSCLC. Dose adjustment is recommended according to pre-defined tolerability criteria. We performed post-hoc analyses on the influence of afatinib dose reduction on adverse events (AEs), pharmacokinetics (PK) and progression-free survival (PFS) in the Phase III LUX-Lung 3 (LL3) trial.

Methods: All pts treated with afatinib in LL3 were included in the analyses (n = 229). Pts were initiated at the protocol-defined and approved dose of 40 mg. For pts experiencing drug-related grade 3 or selected prolonged grade 2 AEs, afatinib was dose reduced by 10 mg decrements to 30 mg or a final dose of 20 mg. Frequency and severity of the most common AEs before and after dose reduction were analysed. Final PK data collected as part of the standard visit schedule (Day 43) were used to compare plasma afatinib concentrations in pts who reduced to 30 mg versus those remaining at 40 mg. PFS was compared between pts who dose reduced within the first 6 months of treatment and those who did not.

Results: Dose reductions occurred in 53% (122/229) of pts; the majority (86%) within the first 6 months of treatment. In pts who dose reduced, decreases in the incidences of drug-related all grade (grade ≥3) AEs were 99.2% (20.5%) to 46.7% (4.1%) for diarrhoea, 88.5% (26.2%) to 38.5% (3.3%) for rash/acne, 77.0% (12.3%) to 27.9% (0%) for stomatitis, and 44.3% (16.4%) to 36.9% (4.9%) for nail effects. Dose reduction was more likely in pts with higher plasma concentrations of afatinib. Median PFS was 11.3 months in pts who dose reduced during the first 6 months of treatment versus 11.0 months in pts who did not (HR = 1.25 [95% CI, 0.91 – 1.72]).

Conclusion: In LL3, tolerability-guided dose adjustment of afatinib was an effective measure to reduce treatment-related AEs without reducing therapeutic efficacy.