Tolerability-guided dose adjustment of afatinib reduced the incidence and severity of adverse drug reactions (ADRs) without affecting efficacy in the LUX-Lung (LL) studies in EGFR mutation-positive (EGFRm+) NSCLC. We evaluated the impact of modifying the recommended starting dose of afatinib (40mg) on efficacy and safety in a real-world setting.
This non-interventional, observational, multi-country/site study used medical records of TKI-naïve patients with EGFRm+ (Del19/L858R) NSCLC treated with first-line afatinib. Primary outcomes were incidence of ADRs, time on treatment (TT), and time to progression (TTP), relative to LL3. Secondary outcomes were percentage of patients with/reasons for modified starting dose.
Overall, 228 patients from 13 countries were included. Baseline characteristics were similar to LL3, but with more Del19 (78% vs. 49%) and fewer Asian patients (44% vs. 72%); 12% had ECOG PS2/3; 31% received afatinib starting doses of <40mg, 20% of whom increased their dose during the study. Of the 40mg starters, 67% underwent dose reductions which occurred more frequently in females, Eastern-Asian patients, and in those with lower body weight. ADRs were the main reason for dose modifications; overall ADR incidence in the
<40mg starters was similar to ≥40mg starters, with fewer ≥G3 ADRs and SAEs than LL3 (28% vs. 49% and 5% vs. 14%, respectively). Median TT and TTP (18.7 and 20.8 months, respectively) were not impacted by dose adjustments. The effectiveness of afatinib was demonstrated across all patient subgroups (ECOG PS0/1 vs. 2/3, age <75 vs. ≥75 years, EGFRm); TT and TTP were significantly longer in patients with ECOG PS0/1 vs. PS2/3.
Dose adjustments with afatinib in real-world practice reduced the frequency and intensity of ADRs without impacting efficacy. A long TT/TTP regardless of afatinib dose adjustments, and an acceptable safety profile highlighted the benefit of tailoring afatinib dose based on individual patient characteristics and ADRs.