How would you approach post-chemoradiation consolidation in a patient with stage III lung adenocarcinoma with an EGFR exon 18 G719A mutation and highly positive PD-L1 level?

Based on currently available FDA-approved therapies, osimertinib is a suitable choice. While G719A is an atypical EGFR TK mutation and some studies show that this variant may be less sensitive to osimertinib compared to the other classic mutations, the same retrospective studies also show clinical efficacy in 30-50% of treated patients; thus, osimertinib is the preferred choice over durvalumab.

Responsiveness of G719X mutations in exon 18 to EGFR-TKIs has been reported (Otsuka et al., PMID 26124334, Leduc et al., PMID 28945865). A combined posthoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6 clinical trials has demonstrated that NSCLC patients harboring G719X had an objective response rate of 77.8% to afatinib, with a PFS of 13.8 months, which was longer than that with chemotherapy but had shorter overall survival than that with chemotherapy (Wu et al., PMID 29178024). A retrospe...