Efficacy of osimertinib resumption with dabrafenib and trametinib for elderly patients with EGFR-mutated lung adenocarcinoma harboring acquired BRAF V600E resistant mutation resistant to osimertinib

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) provides survival benefits in non-small cell lung cancer (NSCLC) with EGFR mutations. The acquired v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation is present in ⁓3% of cases as a resistance mechanism to osimertinib, a third-generation EGFR TKI. However, there is no consensus on the optimal therapy for patients with osimertinib-resistant EGFR-mutated NSCLC harboring a BRAF V600E mutation. Here, we present the case of the oldest patient treated with a combination of osimertinib, dabrafenib, and trametinib. In an 81-year-old woman, osimertinib resumption with reduced doses of dabrafenib and trametinib showed therapeutic efficacy with an acceptable safety profile after osimertinib failure. The present case suggests that under active dose modifications of dabrafenib and trametinib, triple TKI therapy exerts therapeutic effects in elderly patients with osimertinib-resistant EGFR-mutated NSCLC and a BRAF V600E mutation.