The NCCN NSCLC Panel has preference stratified the systemic therapy regimens and decided that afatinib or osimertinib are preferred options for patients with metastatic NSCLC and EGFR L861Q, G719X, and S768I mutation; other recommended options include erlotinib, gefitinib, dacomitinib.

...Mutation in exon 18: G719X(X=A/C/S/D/E), 18del, E709X(X=G/M/V/H/DA/K), V689M, S720P/F, P699S, N700D, E709Q, G721A, V740A, L718P; Mutation in exon 19: Few exon 19 point mutations with unknown structure and kinase activity have been found in EGFR-TKI responders, however, a new class of sensitizing mutations, exon 19 insertions, were recently found, these patients were also eligible for this study: I744_K745insKIPVAI, K745_E746insIPVAIK, K745_E746insVPVAIK, K745_E746insTPVAIK....

Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated....For the major EGFR mutation types, ORR of patients with G719X was 66.7% (95%CI 29.9 to 92.5%) and DCR was 88.9% (95%CI 51.8 to 99.7%).

G719X was the most common mutation in both cohorts, followed by L861Q and S768I in the DC and S768I and L861Q in the AC....The objective response rate (ORR) was significantly higher in the DC than in the AC (60.5 vs. 26.7%, p = 0.008) (Figure 2a). The Kaplan–Meier analysis revealed a longer, albeit not significantly longer, median PFS (mPFS) in the DC than in the AC (12.0 months vs. 10.0 months, p = 0.305) (Figure 2b). The ORRs of subtypes, including mutation category (Figure 2c) and exon category (Figure 2d), were generally higher in the DC than in the AC, especially “other mutation types” in the mutation category (66.7 vs. 9.1%, p = 0.003)....Dacomitinib demonstrated a more favorable efficacy than afatinib in terms of PFS and showed a manageable toxicity profile in patients with NSCLC carrying uncommon EGFR mutations.

In total, 32 NSCLC patients were enrolled between July 2020 and January 2022, and 18 (56.3%) patients received dacomitinib as first-line therapy….The mutations identified were G719X (n = 24; 75%), followed by L861X (n = 10; 31.3%), and S768I (n = 8; 25%). In the first-line setting, 72.2% of patients (13/18) had a confirmed partial response and 100% (18/18) had disease control...56.3% of patients (18/32) had a confirmed partial response and 90.6% (29/32) had disease control, and the median PFS was 10.3 months (95% confidence interval, 6.1–14.5) and the median OS was 36.5 months....Dacomitinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring major uncommon EGFR mutations.