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 20: Including S768I, V765A, T783A, V774A, S784P, R776C, R776H, V765M, G779C, G779F, G779S, T783A, T783I, L798F, L798H, K806E, Q812R, L814P Mutation in exon 21: L861Q, R831H, V834I, L838P, L861R....

Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated....For the four patients with L861Q mutation, ORR was 50.0% (95%CI 6.8 to 93.2%) and DCR was 100% (95%CI 39.8 to 100.0%).

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.

Among the 9 patients with EGFR exon 21 mutated NSCLC in this study, 8 patients harboring L858R mutation while one patients harboring L861Q mutation....They all received low dose of dacomitinib as initial treatment. The ORR was 77.8% and DCR was 100%....Our study showed that dacomitinib (15 mg, once a day) may be also effective for patients harboring EGFR exon 21 mutated NSCLC...