Targeted Therapies and Utility of the Lung-molGPA in Non-Small-Cell Lung Cancer Patients with Brain Metastases

Abstract

Introduction: Therapeutic advances have increased the survival of non-small-cell lung cancer (NSCLC) patients as well as the life-time risk of being diagnosed with brain metastases (BM). Although BM have historically been associated with poor prognosis, it is unclear whether they remain a strong predictor of reduced survival. This study aimed to evaluate the prognostic value of BM and the utility of the Lung-molGPA. Methods: This single-center retrospective database analysis included 1393 NSCLC patients with newly diagnosed BM who registered at the Instituto Nacional de Cancerología of Mexico (INCan) from 2010-2020. The Kaplan–Meier method and log-rank test were used for the survival analysis. Survival times were calculated from the date of NSCLC diagnosis (OS), or BM diagnosis, to the date of death or last follow-up. Cox proportional-hazards models were used to calculate the hazard ratio (HR) for death and the significance of the parameters evaluated. Results: Out of 1058 patients who underwent genetic testing for epidermal growth factor receptor (EGFR) mutations and/or anaplastic lymphoma kinase (ALK) rearrangements, 650 had a positive tumor mutational/rearrangement status (543 had EGFR mutations, 104 had ALK rearrangements, and 3 had both EGFR and ALK alterations). Median OS did not differ between patients with BM and without BM (17.7 months [95% CI, 15.4−19.0] vs 16.6 months [95% CI, 14.3−19.0]; P=0.362). In contrast, the presence of BM was associated with worse OS in patients with a negative tumor mutational status (HR: 1.225 [95% CI, 1.041−1.443]; P=0.015), who did not receive TKI therapy (HR: 1.269 [95% CI, 1.082−1.488]; P=0.003), or with non-adenocarcinoma histology (HR: 1.582 [95% CI, 1.118−2.238]; P=0.01). The median survival after BM diagnosis was 4.27, 6.96, 14.68, and 18.89 months for adenocarcinoma patients with Lung-molGPA scores 0−1, 1.5−2, 2.5−3, and 3.5−4 (P <0.0001). For non-adenocarcinoma patients with Lung-molGPA scores 0−1, 1.5−2, and 2.5−3, the corresponding estimates were 0.95, 2.89, and 9.39 months (P<0.0001). Conclusions: These results show that the prognosis of NSCLC patients with BM is no longer uniformly poor and should be individually assessed. Furthermore, the validity of the Lung-molGPA was confirmed in an independent population from a different geographical region.