I have an 85-year-old female patient with many comorbidities with an ECOG PS of 2 recently diagnosed with stage IV adenocarcinoma of the right upper lung with a right pleural effusion (not sampled), mediastinal adenopathy, and bone metastases. She has no history of tobacco product use. Her tumor ancillary pathology testing has demonstrated an EGFR E709-T710delinsD mutation and a TP53 mutation with no other actionable findings. She does not seem to be a reasonable candidate for chemotherapy. I found limited literature pertaining to her EGFR mutation suggesting superiority of afatinib first generation EGFR TKI therapy but was wondering if you felt that a afatinib, osimertinib, or some other treatment approach would be reasonable for her. She would like to be treated.
Great question. John Heymach's group published a preclinical paper https://www.nature.com/articles/s41586-021-03898-1 putting this mutation as affecting the PACC loop. These mutations are suggested to be more sensitive to the second generation inhibitors. This is supported by a patient series from China with 17 of these mutations and better benefit of afatinib over 1st generation EGFR inhibitors. I would go with the afatinib. It's starting dose has been modified to 30mg daily though this still might be tough for an 85 year old and maybe it is better to start a bit lower.
