Lower Starting Dose of Afatinib for the Treatment of Metastatic Lung Adenocarcinoma Harboring Exon 21 and Exon 19 Mutations

Abstract

BackgroundAfatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib. MethodsWe designed a retrospective study, enrolled all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg afatinib as their starting dose in three Kaohsiung Medical University-affiliated hospitals in TaiwanResultsA total of 179 patients were enrolled in the study, of which 102 (57%) and 77 (43%) received 30 mg and 40 mg afatinib daily as their initial treatment, respectively. The patients initially using 30 mg afatinib daily had a similar RR (74% vs. 82%, p = 0.1661), median PFS (14.5 months vs. 14.80 months, log-rank p = 0.465) and median OS (34 months vs 25.2 months, log-rank p = 0.5982) compared with those initially using 40 mg afatinib daily. Patients with the lower starting dose had fewer ADRs compared with patients receiving 40 mg as their starting dose. The overall incidence of moderate (49% vs 77%, p=0.002) or severe (7% vs 24%, p<0.0001) ADRs was significantly lower in patients receiving 30 mg afatinib compared with those receiving 40 mg. ConclusionPatients receiving 30 mg afatinib as their starting dose had non-inferior RRs, PFS, OS and significantly fewer serious ADRs compared with those patients who received standard 40 mg afatinib as their starting dose.

Metabolic complete tumor response in a patient with epidermal growth factor receptor mutant non-small cell lung cancer treated with a reduced dose of afatinib

“…In fact, more severe AEs were observed in patients who received the standard 40 mg afatinib daily compared with those who received a first-generation EGFR-TKI, such as gefitinib or erlotinib. 31 Therefore, in clinical practice, many clinicians prescribe a lower starting dose of afatinib 32,33 or perform dose modifications 34,35 to improve patient outcomes and adherence, 31 without compromising its beneficial effect.…”

“…Furthermore, a recent clinical trial that enrolled patients with metastatic lung adenocarcinoma who were treated with either 30 mg or 40 mg afatinib daily as first-line treatment demonstrated that patients who received an initial afatinib dose of 40 mg daily required dose reduction (or discontinuation) more frequently than those who initially received 30 mg daily (40% vs. 8%); however, this study did not discriminate between patients with Ex19Dels and those with exon 21 L858R point mutations. 31…”