How would you treat a patient with stage 4 NSCLC with EGFR R776H mutation?

R776H is a rare exon 20 point mutation. Preclinical models suggest that it is an activating mutation and that it is sensitive to erlotinib, afatinib, and osimertinib [Kohsaka et al., PMID 30404555]. Several case studies of patients with rare EGFR mutations have reported responses to EGFR TKIs (erlotinib or afatinib) in patients with a solitary R776H mutation or double mutations (R776H + G724S or G719S or L858R or L861Q) [He et al., PMID 33644199; Kuiper et al., PMID 27875527; Kobayashi et al., P...

This is a challenging EGFR mutation. My two questions:

1) Is the patient a lifelong never smoker or heavy smoker?

2) Is there a co-existing EGFR alteration?

These R776H mutations frequently co-occur with others such as L858R, L861Q, and G719A [Ruan and Kannan, PMID 26101090]. The mutation activates EGFR in a dimerization-dependent manner. Based on pre-clinical models, the R776H equivalent mutations in ErbB2 and ErbB4 are predicted to be activating as well, but whether this translates to efficacy wi...