Tolerability-guided dose adjustment of the kinase inhibitor afatinib reduced treatment-related adverse events without negatively impacting efficacy in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC), according to results from a study presented at the European Lung Cancer Conference (ELCC) 2016.1

The U.S. Food and Drug Administration (FDA)-approved dose for first-line afatinib in patients with EGFR mutation-positive NSCLC is 40 mg/day; however, the dose can be adjusted based on individual tolerability. Therefore, researchers sought to assess the impact of afatinib dose adjustment on adverse events, pharmacokinetics, and progression-free survival.

For the post-hoc analysis, researchers examined data from the LUX-Lung 3 and LUX-Lung 6 studies, which included 229 and 239 afatinib-treated patients, respectively. Participants who experienced a treatment-related grade 3 or selected prolonged grade 2 adverse event with afatinib 40 mg could be dose-reduced in 10 mg increments to a minimum of 20 mg.

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Results showed that dose reductions occurred in 53% of afatinib-treated patients in LUX-Lung 3 and 28% of afatinib-treated patients in LUX-Lung 6, with the majority experienced within the first 6 months of treatment.

Researchers found that dose reduction resulted in decreases in the incidence and severity of EGFR-mediated drug-related adverse events, such as diarrhea, rash/acne, stomatitis, and nail changes.

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In terms of efficacy, median progression-free survival was 11.3 months for patients who dose reduced during the first 6 months of treatment compared with 11.0 months for those who did not dose reduce among patients of the LUX-Lung 3 trial (hazard ratio [HR], 1.25; 95% CI, 0.91-1.72). Similarly, median progression-free survival was 12.3 months and 11.0 months, respectively, in the LUX-Lung 6 study (HR, 1.00; 95% CI, 0.69-1.46).


  1. Schuler M, Yang J, Sequist LV, et al. Impact of dose adjustment on the safety and efficacy of afatinib in patients (pts) with advanced EGFR mutation-positive non-small cell lung cancer (NSCLC): Post-hoc analyses of LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6). Poster presentation at: European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland.