Two Cases of Epidermal Growth Factor Receptor L861R Mutation-Positive Lung Adenocarcinoma Treated With Osimertinib and Afatinib.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are detected in approximately 40%-50% of patients with lung adenocarcinoma in Asian populations and in around 10% of patients in Western populations. Among these, the EGFR L861R mutation is uncommon and undetectable using conventional polymerase chain reaction methods. Recently, clinically available next-generation sequencing (NGS) has been used to detect L861R mutations, potentially increasing the number of identified cases of L861R-positive non-small cell lung cancer. Herein, we present two cases of EGFR L861R-mutated lung adenocarcinoma treated with afatinib and osimertinib to evaluate the clinical efficacy and tolerability of these targeted therapies. CASE: Case 1: A 63-year-old man with lung adenocarcinoma harboring an EGFR L861R mutation (cStage IVB) received afatinib 40 mg/day. Computer tomography (CT) on Day 49 showed shrinkage of the primary tumor, accompanied by a decrease in tumor markers. The afatinib dose was reduced to 30 mg/day due to Grade 1 diarrhea and an acneiform rash. Ground-glass opacities were subsequently observed around the tumor. Although pneumonitis was initially suspected, the findings were subsequently considered consistent with carcinomatous lymphangitis. Consequently, afatinib was discontinued on Day 56. Case 2: An 83-year-old man with lung adenocarcinoma harboring an EGFR L861R mutation (cStage IVB) received osimertinib 80 mg/day. Afatinib was avoided due to concerns regarding tolerability in the elderly. CT imaging on Day 14 showed tumor shrinkage with reduced attenuation and decreased levels of tumor markers. However, osimertinib was discontinued on Day 104 due to a Grade 3 skin rash. The response to osimertinib was evaluated as stable disease. Following treatment discontinuation, the disease progressed to multiple brain metastases, and supportive care was initiated. CONCLUSION: Here, we present the first case showing the anti-tumor efficacy of afatinib and the second case showing the anti-tumor efficacy of osimertinib in a patient with EGFR L861R-positive lung adenocarcinoma. Despite their short treatment durations, afatinib and osimertinib may have potential clinical activity in patients with EGFR L861R-positive lung cancer.