A Need for More Molecular Profiling in Brain Metastases.

As local disease control improves, the public health impact of brain metastases (BrM) continues to grow. Molecular features are frequently different between primary and metastatic tumors as a result of clonal evolution during neoplasm migration, selective pressures imposed by systemic treatments, and differences in the local microenvironment. However, biomarker information in BrM is not routinely obtained despite emerging evidence of its clinical value. We review evidence of discordance in clinically actionable biomarkers between primary tumors, extracranial metastases, and BrM. Although BrM biopsy/resection imposes clinical risks, these risks must be weighed against the potential benefits of assessing biomarkers in BrM. First, new treatment targets unique to a patient's BrM may be identified. Second, as BrM may occur late in a patient's disease course, resistance to initial targeted therapies and/or loss of previously identified biomarkers can occur by the time of occult BrM, rendering initial and other targeted therapies ineffective. Thus, current biomarker data can inform real-time treatment options. Third, biomarker information in BrM may provide useful prognostic information for patients. Appreciating the importance of biomarker analyses in BrM tissue, including how it may identify specific drivers of BrM, is critical for the development of more effective treatment strategies to improve outcomes for this growing patient population.
Competing Interests: CA receives research funding from PUMA, Lilly, Merck, Seattle, Genetics, Nektar, Tesaro, G1-Therapeutics, ZION, Novartis, and Pfizer; a compensated consultant role from Genentech (1/2019–), Eisai (1/2019–), IPSEN (2/2019–), Seattle Genetics (11/15/2019–11/15/2020), Astra Zeneca (3/2020–6/2020), Novartis (5/2020–5/2022), Immunomedics (10/1/2020–9/22/2021), Elucida (9/2020), and Athenex (2/2021–2/2023); and royalties from UpToDate and Jones and Bartlett. AS receives research funding (paid to institution) from Bristol Myers Squibb, Immunocore and Merck and a compensated consultant role from Novartis, Pfizer, Iovance, and Regeneron. ZR receives royalties for intellectual property related to cancer molecular diagnostic testing that has been licensed to Genetron Health and is managed by Duke University. JC receives research funding (as PI) from Bristol-Myers Squibb, Genentech, Spectrum, Adaptimmune, Medpacto, Bayer, AbbVie, Moderna, GlaxoSmithKline, Array, AstraZeneca, Grid Therapeutics, and CBMG; speaker at Merck and AstraZeneca; adviser at AstraZeneca (10/2018, 10/26/19), Guardant (12/18/18), Merck (3/8/19), Pfizer (1/10/20), NGM Biopharmaceuticals (1/20/20), Spectrum (9/18/20), Genentech (11/1/20); travel from Merck, AstraZeneca, Pfizer, and NGM Bio; Board of Directors at Lung Cancer Initiative of North Carolina (uncompensated); and DMSC at G1 Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Shen, Van Swearingen, Price, Bulsara, Verhaak, Baëta, Painter, Reitman, Salama, Clarke, Anders, Fecci, Goodwin and Walsh.)