Introduction Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). However, questions remain about the optimal treatment sequence of EGFR TKIs. The global, observational GioTag study demonstrated prolonged time on treatment with sequential afatinib and osimertinib therapy in patients who acquired the T790M mutation. Here, we assessed outcomes in patients who received the approved 40-mg starting dose of afatinib, as used in the clinical trial setting. Methods In the non-interventional, global, multicenter GioTag study, patients had T790M-positive disease following first-line afatinib and started osimertinib treatment ≥ 10 months prior to data entry. Primary outcome was time on treatment. This subanalysis assessed outcomes in patients who received afatinib 40 mg. Results In 169 patients who received an afatinib starting dose of 40 mg, median time on treatment was 27.6 months (90% confidence interval [CI] 26.3–31.3). Benefit was seen across patient subgroups, particularly those with Del19-positive disease and Asian patients; median time on treatment was 29.9 months (90% CI 27.6–46.7) in patients with Del19-positive disease and 46.7 months (90% CI 28.4–not reached) in Asian patients. The 2-year overall survival rate was 80%. Conclusions These real-world results support the overall study results and demonstrate prolonged time on treatment with sequential afatinib and osimertinib. The results suggest that sequential afatinib and osimertinib is a feasible therapeutic strategy for patients who acquire the T790M mutation, particularly those with Del19-positive disease or Asian patients. Trial Registration Number NCT03370770. Electronic Supplementary Material The online version of this article (10.1007/s12325-019-01187-y) contains supplementary material, which is available to authorized users.