Brain metastases in Japanese NSCLC patients: prognostic assessment and the use of osimertinib and immune checkpoint inhibitors: a retrospective study

Background: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not yet been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed. Methods: We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and received radiotherapy for BM initially at the Hokkaido Cancer Center. Lung-molGPA items, sequence of therapy, use of osimertinib, expression of PD-L1 (classified as high, low, and no) and use of immune checkpoint inhibitors (ICI) were evaluated for influence. The main outcome measure was survival from the day of diagnosis of BM, and log-rank tests were performed to compare the results. Results: The median survival times for adenocarcinoma by groupings of GPA score (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p<0.0001), respectively. The median survival times for non-adenocarcinoma by groupings of GPA score (0‒1.0, 1.5‒2.0, and 2.5‒3.0) Group were 3.2, 11.0, and 16.0 months (p=0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome. The median survival times for the group with and without osimertinib treatment were 34.2 and 17.6 months, respectively (p=0.0164). In a comparison of treatment sequences, no significant differences were found between groups; however, patients who received both irradiation and tyrosine-kinase inhibitor for BM had better prognoses than patients with only irradiation for BM (35.8 months vs 14.8 months, p=0.0007). In patients tested for PD-L1 expression, the median survival times after diagnosis of brain metastasis were 5.6, 22.5, and 9.3 months for high-, low- and no-expression groups (p=0.2198), respectively. Also, in patients with high PD-L1 expression, those with ICI had better survival (median OS, 8.6 months) than those without (median OS, 3.6 months). Conclusions: We conformed that Lung-molGPA successfully classified Japanese NSCLC patients with brain metastasis by prognosis. Osimertinib was shown to extend survival of EGFR-positive NSCLC patients with BM, and ICI proved effective in patients with high PD-L1 expression.Trial registration: Not applicable