Afatinib in EGFR TKI-naïve patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer: Interim analysis of a Phase 3b study

Abstract

Randomized controlled trials have demonstrated that afatinib is a suitable treatment option for patients with epidermal growth factor receptor mutation-positive (EGFRm +) non-small cell lung cancer (NSCLC). However, such studies often exclude patients treated in routine clinical practice. We report interim results from a Phase 3b, open-label, multicenter, single-arm, exploratory trial, in which afatinib was investigated in a realworld setting. Materials and methods: Patients with EGFRm + tyrosine kinase inhibitor (TKI)-naïve NSCLC received afatinib 40 mg orally, once-daily, until disease progression, or voluntary withdrawal. Primary objective was safety. Results: Overall, 479 patients received afatinib: median age 65 years, 8 % of patients had an ECOG performance status ≥ 2, 17 % had brain metastases, and 13 % had tumors containing uncommon mutations only. All but one patient (99.8 %) had an adverse event (AE). Treatment-related AEs (TRAEs; any/grade ≥ 3) occurred in 97 %/44 % of patients; most common were diarrhea (87 %/16 %) and rash (51 %/11 %). AEs leading to afatinib dose-reduction were reported in 258 patients (54 %), and 37 patients (8 %) discontinued treatment due to a TRAE. Objective response rate was 45.5 %, median duration of response was 14.1 months (95 % CI: 12.2-16.4). Overall median time to symptomatic progression and progression-free survival were 14.9 months (95 % CI: 13.8-17.6) and 13.4 months

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

“…The median PFS and OS of patients with brain or bone metastatic sites are around 8.0–9.0 months and 20.0–25.0 months respectively, and the median PFS and OS of patients with liver metastasis are around 6.7 months and 9.2–13.4 months, respectively [ 12 , 13 ], although the median PFS and OS of patients without these metastatic sites are around 11.0–15.0 months and 17.5–38.0 months, respectively. Additionally, the clinical efficacy of afatinib in patients with brain metastasis is reported to be shorter than that in patients without brain metastasis (10.1 vs 13.9 months) [ 14 ]. These results indicate that metastatic sites of EGFR -mutant NSCLC are critical factors for EGFR-TKI efficacy and directly affect patient outcomes.…”

Comparison of T790M Acquisition After Treatment With First- and Second-Generation Tyrosine-Kinase Inhibitors: A Systematic Review and Network Meta-Analysis

“…Erlotinib as the first line of treatment for NSCLC patients with sensitive EGFR gene mutations revealed an ORR of 58–83%, PFS of 9.7–13 months, and OS of 23–33 months ( 5 ). Afatinib is an irreversible covalent inhibitor of the ErbB receptor family, which includes EGFR, ErbB2/HER2, and ErbB4/HER4 ( 6 ). It was approved by the FDA for treating NSCLC patients with exon 21 L858R substitutions and exon 19 deletions in 2013 and for uncommon EGFR mutations such as L861Q in exon 21 and G719X in exon 18 in 2018 ( 6 ).…”

Afatinib in EGFR TKI-Naïve Patients with Locally Advanced or Metastatic EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Pooled Analysis of Three Phase IIIb Studies

“…To date, available real-world evidence suggests that afatinib is effective and tolerable in diverse patient populations treated in routine clinical practice (14)(15)(16)(17)(18). Here, in order to assess outcomes in a larger cohort, we report a combined analysis of three phase IIIb studies of afatinib in EGFR TKI-naïve patients with EGFRm+ NSCLC treated in a setting similar to daily clinical practice (19,20).…”