J-REGISTER: real-world study of Japanese patients with <i>EGFR</i> mutation-positive NSCLC treated with first-line afatinib

The J-REGISTER study assessed outcomes and subsequent treatment in patients with <i>EGFR</i> mutation-positive NSCLC treated with first-line afatinib, including patients with uncommon <i>EGFR</i> mutations. This retrospective study assessed 805 patients treated with afatinib in Japan. The primary objective was time on treatment with afatinib. Other objectives included time on treatment from initiation of afatinib until the end of second-line therapy, and overall survival. Median time on treatment with afatinib was 13.4 months (14.3/10.1 months in patients with common/uncommon mutations). Median overall time on treatment was highest in patients who received sequential afatinib and osimertinib (32.8 months). Median overall survival was 41.2 months. Afatinib is an effective first-line treatment option for Japanese patients with <i>EGFR</i> mutation-positive NSCLC. NCT04795245. This study describes treatment patterns in patients with a type of lung cancer that is caused by a mutation in a gene called the epidermal growth factor receptor (<i>EGFR</i>). Many kinds of <i>EGFR</i> mutations have been identified and are grouped as “common” or “uncommon” mutations. Patients with <i>EGFR</i> mutation-positive cancer are usually treated with tablets called EGFR tyrosine kinase inhibitors (TKIs), which are very effective at silencing abnormal forms of EGFR that drive tumor growth. Unfortunately, tumors may eventually become resistant to EGFR TKIs and alternative treatments are required (named “second-line treatments”). There are several types of EGFR TKI available: first-generation (e.g. gefitinib, erlotinib); second-generation (e.g. afatinib, dacomitinib) and third-generation (osimertinib) TKIs. A few unanswered questions remain regarding the optimal use of EGFR TKIs. Firstly, which EGFR TKI is most effective against uncommon <i>EGFR</i> mutations and, secondly, what is the most effective second-line treatment after first-line treatment with an EGFR TKI? In this study, we reviewed treatment patterns in 805 patients with lung cancer in Japan who received afatinib. We found that half of patients remained on treatment for at least 13 months, providing further evidence that afatinib is an effective therapy. Afatinib was effective in patients with uncommon and common <i>EGFR</i> mutations. The most common second-line treatment after afatinib was chemotherapy. Approximately a third of patients received another EGFR TKI after afatinib, most commonly osimertinib, which was the most effective second-line treatment. Sequential afatinib and osimertinib treatment should be considered. In a real-world study in 805 Japanese patients with<i>EGFR</i> mutation-positive NSCLC treated with first-line afatinib, afatinib appeared to be effective in patients with common and uncommon <i>EGFR</i> mutations. The most effective subsequent treatment option was osimertinib.