Median age of EGFR/ALK+ NSCLC BM patients was 60 years (range 29.8-82.6 y) and ~50% (n = 44) had Karnofsky performance status (KPS) score >80.Median number of BM was 2 (1 to ≥99).
Osimertinib is a tyrosine kinase inhibitor (TKI) of the mutated epidermal growth factor receptor (EGFRm) with observed efficacy in patients with brain metastases.
Number of BM does not impact outcomes in the EGFR/ALK+ NSCLC patients, implying that targeted therapy along with surgery and/or radiation may improve OS irrespective of the number of BM.
We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed.
Compared with ALK-rearranged or EGFR-mutant NSCLC, ROS1-rearranged NSCLC was less likely to present with extrathoracic metastases (ROS1, 49%; ALK, 75%; EGFR, 72%; P < .01), including brain metastases (ROS1, 9%; ALK, 25%; EGFR, 40%; P < .04).
Compared with ALK-rearranged or EGFR-mutant NSCLC, ROS1-rearranged NSCLC was less likely to present with extrathoracic metastases (ROS1, 49%; ALK, 75%; EGFR, 72%; P < .01), including brain metastases (ROS1, 9%; ALK, 25%; EGFR, 40%; P < .04).
The results of this study suggest that the brain-penetrant PI3K/mTOR targeting GDC-0084 is a promising treatment option for breast cancer brain metastases with dysregulated PI3K/mTOR signaling pathway conferred by activating <i>PIK3CA</i> mutations.
The present study was designed to ascertain whether CuE inhibits YAP and its downstream gene expression in the human NSCLC cell lines H2030‑BrM3 (K‑rasG12C mutation) and PC9‑BrM3 (EGFRΔexon19 mutation), which have high potential for brain metastasis.
Kaplan Meier analysis showed that clinical stage and brain metastasis were significantly associated with OS (both P<0.05), but neither KRAS exon 3 mutation nor PTEN exon 7 mutation was significantly associated with OS (P>0.05).
After adjusting covariables, EGFR mutations were associated with BM in never-smokers (adjusted OR = 2.07, 95% CI = 1.02-4.34) and K-RAS mutations were risk factors for BM in males (adjusted OR = 3.86, 95% CI = 1.01-14.43).
Epidermal Growth Factor Receptor Mutation Status Confers Survival Benefit in Patients with Non-Small-Cell Lung Cancer Undergoing Surgical Resection of Brain Metastases: A Retrospective Cohort Study.
Mutations of major drivers, including EGFR, KRAS, TP53, and ALK, were highly concordant between primary NSCLC and matched BMs (>80%), whereas discordance suggested the unique genomic evolution and oncogenic mechanisms of NSCLC BMs.
Furthermore, RET and HER2 inhibition in a PDX model of BrM led to a statistically significant antitumor response vs control (n = 4, % tumor growth inhibition [mean difference; SD], anti-RET = 86.3% [1176; 258.3], P < .001; anti-HER2 = 91.2% [1114; 257.9], P < .01).
Patients with breast cancer who were ≤45 years regardless of HER2 status or had HER2<sup>+</sup> disease regardless of age and underwent SRS for brain metastases were included.
Regarding molecular factors, all driver mutations in lung adenocarcinoma had a favorable effect (EGFR, HR 0.53, 95%CI 0.31-0.89; ALK, HR 0.28, 95%CI 0.12-0.66; KRAS, HR 0.65, 95%CI 0.47-0.92), triple negative status predicted poor prognosis in breast adenocarcinoma (HR 2.04, 95%CI 1.13-3.69), while no effect of BRAF/NRAS mutations was demonstrated in melanoma BMs.
The results of this study suggest that the brain-penetrant PI3K/mTOR targeting GDC-0084 is a promising treatment option for breast cancer brain metastases with dysregulated PI3K/mTOR signaling pathway conferred by activating <i>PIK3CA</i> mutations.