Abstract
Background: Afatinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), is approved for first-line therapy in advanced EGFR mutation–positive non-small-cell lung cancer (NSCLC) and has previously demonstrated activity after failure of chemotherapy and reversible EGFR TKI, with improved response and progression-free survival, compared with placebo. Outcomes in pretreated patients with advanced NSCLC receiving afatinib through a Canadian special access program (sap) are reported here. Methods: Patients with NSCLC progressing after at least 1 line of chemotherapy and an EGFR TKI were eligible to enrol in the sap. Characteristics of patients from the two largest accruing Canadian centres were retrospectively reviewed, including demographics, disease and treatment data, and patient outcomes. Results: The 53 patients who received afatinib (57% women, 51% never-smokers, 26% of East Asian ethnicity, and 66% with adenocarcinoma) had a median age of 59 years. EGFR mutations were documented in 25%, and EGFR wildtype in 8%. All patients had received prior EGFR TKI treatment, with 42% achieving a response. Patients took afatinib for a median of 2 months (range: 0–26 months); 17% required 1 or more dose reductions. Of 47 evaluable patients receiving afatinib, 10 experienced tumour shrinkage, and 11, stable disease. Median survival from afatinib initiation was 5 months (95% confidence interval: 2 months to 8 months). Grade 3 or greater diarrhea, rash, paronychia, and stomatitis were seen in 9%, 11%, 6%, and 4% of patients respectively. Conclusions: In an unselected population of pretreated patients with advanced NSCLC after TKI failure, median survival with afatinib therapy was 5 months. Through a sap, afatinib demonstrated activity in clinical practice, with manageable toxicity.