A Durable Response to Low-Dose Afatinib After Progression on Osimertinib in Advanced Epidermal Growth Factor Receptor (EGFR) L861Q-Mutated Lung Adenocarcinoma: A Case Report.

Although both afatinib and osimertinib have demonstrated clinical activity in treatment-naive non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations, the efficacy and safety of afatinib after progression on osimertinib remain unclear. A 68-year-old man with stage IVA lung adenocarcinoma harboring an uncommon EGFR L861Q mutation and a programmed death-ligand 1 (PD-L1) tumor proportion score of <1% received first-line osimertinib (80 mg once daily) for nine months, achieving a partial response before disease progression. As second-line therapy, he was treated with pembrolizumab plus carboplatin and pemetrexed for four cycles, followed by 13 cycles of maintenance pembrolizumab and pemetrexed, and subsequently five cycles of pembrolizumab monotherapy, maintaining stable disease until further progression. He was then started on low-dose afatinib (20 mg once daily) as third-line therapy, achieving a partial response that has been maintained for 18 months without severe adverse events. This case suggests that low-dose afatinib may provide durable disease control with acceptable tolerability after progression on osimertinib in advanced EGFR L861Q-mutated NSCLC.