Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers Journal Article
| Authors: | Offin, M.; Feldman, D.; Ni, A.; Myers, M. L.; Lai, W. V.; Pentsova, E.; Boire, A.; Daras, M.; Jordan, E. J.; Solit, D. B.; Arcila, M. E.; Jones, D. R.; Isbell, J. M.; Beal, K.; Young, R. J.; Rudin, C. M.; Riely, G. J.; Drilon, A.; Tabar, V.; DeAngelis, L. M.; Yu, H. A.; Kris, M. G.; Li, B. T. |
| Article Title: | Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers |
| Abstract: | Background: Mutations in human epidermal growth factor receptor 2 (HER2; also known as ERBB2) are found in approximately 2% of lung adenocarcinomas. The frequency and clinical course of brain metastases in this oncogenic subset are ill defined. Methods: Baseline and subsequent development of brain metastases was evaluated in consecutive patients with HER2-mutant (n = 98), epidermal growth factor receptor (EGFR)–mutant (n = 200), and KRAS-mutant lung cancers (n = 200). Results: At metastatic diagnosis, the odds ratio (ORs) for brain metastases was similar for patients whose tumors harbored HER2 mutations (19%) in comparison with patients with KRAS mutations (24%; OR for HER2 vs KRAS, 0.7; P =.33) but lower compared to patients with EGFR mutations (31%; OR for HER2 vs EGFR, 0.5; P =.03). Patients with lung cancer and HER2 mutations developed more brain metastases on treatment than patients with KRAS mutations (28% vs 8%; hazard ratio [HR], 5.2; P <.001) and trended more than patients with EGFR mutations (28% vs 16%; HR, 1.7; P =.06). Patients with HER2 YVMA mutations also developed more brain metastases on treatment than patients with KRAS mutations (HR, 5.9; P <.001). The median overall survival (OS) was shorter for patients with HER2-mutant (1.6 years; P <.001) or KRAS-mutant lung cancers (1.1 years; P <.001) than patients with EGFR-mutant lung cancers (3.0 years). Brain metastases occurred in 47% of patients with HER2-mutant lung cancers, which imparted shorter OS (HR, 2.7; P <.001). Conclusions: These data provide a framework for brain imaging surveillance in patients with HER2-mutant lung cancers and underpin the need to develop HER2-targeted agents with central nervous system activity. © 2019 American Cancer Society |
| Keywords: | adult; aged; gene mutation; major clinical study; overall survival; mutation; disease course; cancer growth; comparative study; neuroimaging; lung neoplasms; morbidity; epidermal growth factor receptor; epidermal growth factor receptor 2; cohort analysis; lung cancer; oncogenes; brain metastasis; cancer epidemiology; receptor; egfr gene; k ras protein; electroencephalogram; erbb-2; molecularly targeted therapy; clinical outcome; kras gene; her2 gene; human; male; female; priority journal; article |
| Journal Title: | Cancer |
| Volume: | 125 |
| Issue: | 24 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2019-12-15 |
| Start Page: | 4380 |
| End Page: | 4387 |
| Language: | English |
| DOI: | 10.1002/cncr.32461 |
| PUBMED: | 31469421 |
| PROVIDER: | scopus |
| PMCID: | PMC6891113 |
| DOI/URL: | |
| Notes: | Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work