Group A complex u-EGFRm consisted of double mutations of G719X+E709F, G719X+S768I, G719X+L861Q, L858R+T790M, L858R+S768I, L858R+S765I, del19+S768I, del19+L747S, or R776C+L861Q...Response was significantly higher in groups A (70%) and C (54%) compared to B (13%; pairwise comparison P < .001 and .008, respectively)....In clinical practice, afatinib was active in patients with u-EGFRm NSCLC, particularly in complex and single mutations.

U-EGFRm were analysed as complex mutations (Group A), Ins20 (Group B), or single mutations (Group C). Group A complex u-EGFRm consisted of double mutations of G719X+E709F, G719X+S768I, G719X+ L861Q, L858R+T790M, L858R+S768I, Del19+S768I, Del19+L747S, or R776C+L861Q. Response to afatinib was significantly higher in Group A and C (70% and 54%, respectively), compared with Group B (13%; pairwise comparison p < 0.001 and 0.013, respectively). Median OS for the entire cohort was 19.9 m (9.7-30.1). Hazard ratio for OS were 0.27 (95% CI 0.10-0-71, p = 0.009) and 0.40 (95% CI 0.17-0.95, p = 0.037) for Group A and C compared to Group B, respectively. afatinib was active in u-EGFRm NSCLC , particularly in complex and single mutations.

Afatinib was well tolerated with no new safety signals, and efficacy was encouraging in Korean patients with EGFRm+ NSCLC, including those with baseline brain metastases and/or uncommon EGFR mutations....Overall, patients with tumors harboring mutations in exon 20 (alone or as a compound mutation) had a lower ORR [26.7% (1 CR and 3 PRs among 15 patients)] compared with those with tumors harboring mutations in exons 18, 19, and 21 only (Figure 1). Afatinib showed strong activity against compound mutations, including an ORR of 100% in four patients with tumors harboring mutations in both exon 18 and 21 (Figure 1)...patients may appear in >1 category; specific mutations include: G719X (exon 18), Del19 (exon 19), S768I (exon 20), L858R and L861Q (exon 21).