The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases

Abstract

Purpose Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). Methods A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. Results Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR−/+ was 10/15 months (P=.02) and for ALK−/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK−, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naïve patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P=.84]/1.60 [P=.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD. Conclusion EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.

Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial

“…Mutations in epidermal growth factor receptor are more prevalent among the Japanese population and are associated with delayed onset of brain metastases and longer survival after treatment. (11, 12) Further study of adjuvant WBRT may warrant attention to gene alterations.…”

Estimating prognosis at the time of repeat whole brain radiation therapy for multiple brain metastases: The reirradiation score

“…Recently, the impact of biomarkers on prognostication for patients with BM from primary breast and NSCLC has led to modifications of the GPA. 34 , 35 This information is not available within the current cohort, which may also be a limitation; however, in practice, these data may either be unavailable or rendered irrelevant once patients have progressed through all available lines of systemic therapy. Additionally, we were unable to abstract quality of life, steroid dependence, setting of care, and KPS after completion of repeat WBRT.…”

Applicability of graded prognostic assessment of lung cancer using molecular markers to lung adenocarcinoma patients with brain metastases

“…However, independent prognostic factors vary depending on the primary tumor site, and other biological makers may also play roles. The recently published NSCLC-specific Lung-molGPA index is the first to incorporate both traditional factors, such as patient age and gender, and EGFR and ALK mutation status [ 16 , 17 ]. Our assessment showed that the Lung-molGPA index offers medium OS predictive ability in lung adenocarcinoma patients with BMs.…”

“…To further refine the NSCLC-specific GPA, a new prognostic system, Lung-molGPA, was proposed based on 2,186 NSCLC patients with BMs. This new system included not only age, KPS, extracranial metastases, and number of BMs, but also EGFR and ALK mutation status [ 16 , 17 ].…”