medwireNews: Afatinib is effective when given to patients with non-small-cell lung cancer (NSCLC) who have progressed during treatment with erlotinib and/or gefitinib, phase II trial results reveal.
Although response rates were modest, the data support the potential value of afatinib in patients with advanced epidermal growth factor receptor (EGFR)-mutant tumors who have developed resistance to EGFR tyrosine kinase inhibitor therapy.
The trial included 62 patients with stage IIIB/IV pulmonary adenocarcinoma, of whom 45 (72.6%) tested positive for EGFR mutations. All patients had received at least 12 weeks’ treatment with erlotinib and/or gefitinib in the third- or fourth-line setting; 51 (82.3%) patients were considered to have acquired resistance to these therapies.
All patients were started on afatinib, an oral irreversible ErbB family blocker, at a dose of 50 mg/day until progressive disease or intolerable toxicity; the mean duration of treatment was 4.59 months.
Of 61 evaluable patients, five (8.2%) achieved a partial response and 35 (57.4%) had stable disease for at least 6 weeks, giving a disease control rate of 65.6%.
Most responses occurred within 8 weeks of starting afatinib and the mean duration of response was 24.4 weeks, note Nobuyuki Katakami (Kobe City Medical Center General Hospital, Japan) and colleagues, writing in the Journal of Clinical Oncology.
Afatinib reduced the size of target lesions in 79% of patients, with nine (16%) patients having at least a 30% reduction in tumor size. Median progression-free survival was 4.4 months and median overall survival was 19.0 months.
Subgroup analysis found that the treatment benefit was consistent irrespective of patient gender, type of prior therapy, number of previous chemotherapy regimens, and mutation type.
The most common toxicities were diarrhea, rash/acne, and stomatitis, with frequencies of 100%, 91.9%, and 85.5%, respectively. Around two thirds of patients required a reduction in their afatinib dose and 18 (29.0%) patients discontinued afatinib due to treatment-related adverse effects. There were no drug-related deaths.
Noting that there is a growing need for new molecular targeted agents that address the issue of resistance to erlotinib and gefitinib, Katakami and co-authors say that afatinib has shown “modest but noteworthy efficacy.”
They write: “Further evaluation of the potential of afatinib in patients with advanced NSCLC will be addressed by the LUX-Lung phase III clinical trial program and the ongoing study of the afatinib plus cetuximab combination in the resistance setting.”
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