New Classifications and Emerging Treatments in Brain Cancer

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New Classifications and Emerging Treatments in Brain Cancer
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Margaret O. Johnson, MD, MPH

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References
  1. Sokolov AV et al. Pharmacol Rev. 2021;73(4):1-32. doi:10.1124/pharmrev.121.000317
  2. Louis DN et al. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
  3. Mellinghoff IK et al. Clin Cancer Res. 2021;27(16):4491-4499. doi:10.1158/1078-0432.CCR-21-0611
  4. Woo C et al. JCO Clin Cancer Inform. 2021;5:985-994. doi:10.1200/CCI.21.00052
  5. Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO). ClinicalTrials.gov. Updated May 17, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04164901
  6. Servier's pivotal phase 3 indigo trial investigating vorasidenib in IDH-mutant low-grade glioma meets primary endpoint of progression-free survival (PFS) and key secondary endpoint of time to next intervention (TTNI) (no date) Servier US. March 14, 2023. Accessed March 20, 2023. https://www.servier.us/serviers-pivotal-phase-3-indigo-trial-meets-primary-endpoint
  7. Nehra M et al. J Control Release. 2021;338:224-243. doi:10.1016/j.jconrel.2021.08.027
  8. Hersh AM et al. Cancers (Basel). 2022;14(19):4920. doi:10.3390/cancers14194920
  9. Shoaf ML, Desjardins A. Neurotherapeutics. 2022;19(6):1818-1831. doi:10.1007/s13311-022-01256-1
  10. Bagley SJ, O’Rourke DM. Pharmacol Ther. 2020;205:107419. doi:10.1016/j.pharmthera.2019.107419
  11. Batich KA et al. Clin Cancer Res. 2020;26(20):5297-5303. doi:10.1158/1078-0432.CCR-20-1082
  12. Lin J et al. Cancer. 2020;126(13):3053-3060. doi:10.1002/cncr.32884
  13. Barth SK et al. Cancer Epidemiol. 2017;50(pt A):22-29. doi:10.1016/j.canep.2017.07.012
  14. VA and partners hope APOLLO program will be leap forward for precision oncology. US Department of Veteran Affairs. May 1, 2019. Accessed December 8, 2022. https://www.research.va.gov/currents/0519-VA-and-partners-hope-APOLLO-program-will-be-leap-forward-for-precision-oncology.cfm
  15. Konteatis Z et al. ACS Med Chem Lett. 2020;11(2):101-107. doi:10.1021/acsmedchemlett.9b00509
Author and Disclosure Information

Margaret O. Johnson, MD, MPH
Neuro-oncologist, National TeleOncology and National Precision Oncology Program
Veterans Health Administration
Assistant Professor of Neurosurgery,
Preston Robert Tisch Brain Tumor Center,
Duke University School of Medicine
Durham, NC

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Neurology
Cancer
Author(s)
Margaret O. Johnson, MD, MPH
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Margaret O. Johnson, MD, MPH
Author and Disclosure Information

Margaret O. Johnson, MD, MPH
Neuro-oncologist, National TeleOncology and National Precision Oncology Program
Veterans Health Administration
Assistant Professor of Neurosurgery,
Preston Robert Tisch Brain Tumor Center,
Duke University School of Medicine
Durham, NC

Author and Disclosure Information

Margaret O. Johnson, MD, MPH
Neuro-oncologist, National TeleOncology and National Precision Oncology Program
Veterans Health Administration
Assistant Professor of Neurosurgery,
Preston Robert Tisch Brain Tumor Center,
Duke University School of Medicine
Durham, NC

Click to view more from Cancer Data Trends 2023.

Click to view more from Cancer Data Trends 2023.

References
  1. Sokolov AV et al. Pharmacol Rev. 2021;73(4):1-32. doi:10.1124/pharmrev.121.000317
  2. Louis DN et al. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
  3. Mellinghoff IK et al. Clin Cancer Res. 2021;27(16):4491-4499. doi:10.1158/1078-0432.CCR-21-0611
  4. Woo C et al. JCO Clin Cancer Inform. 2021;5:985-994. doi:10.1200/CCI.21.00052
  5. Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO). ClinicalTrials.gov. Updated May 17, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04164901
  6. Servier's pivotal phase 3 indigo trial investigating vorasidenib in IDH-mutant low-grade glioma meets primary endpoint of progression-free survival (PFS) and key secondary endpoint of time to next intervention (TTNI) (no date) Servier US. March 14, 2023. Accessed March 20, 2023. https://www.servier.us/serviers-pivotal-phase-3-indigo-trial-meets-primary-endpoint
  7. Nehra M et al. J Control Release. 2021;338:224-243. doi:10.1016/j.jconrel.2021.08.027
  8. Hersh AM et al. Cancers (Basel). 2022;14(19):4920. doi:10.3390/cancers14194920
  9. Shoaf ML, Desjardins A. Neurotherapeutics. 2022;19(6):1818-1831. doi:10.1007/s13311-022-01256-1
  10. Bagley SJ, O’Rourke DM. Pharmacol Ther. 2020;205:107419. doi:10.1016/j.pharmthera.2019.107419
  11. Batich KA et al. Clin Cancer Res. 2020;26(20):5297-5303. doi:10.1158/1078-0432.CCR-20-1082
  12. Lin J et al. Cancer. 2020;126(13):3053-3060. doi:10.1002/cncr.32884
  13. Barth SK et al. Cancer Epidemiol. 2017;50(pt A):22-29. doi:10.1016/j.canep.2017.07.012
  14. VA and partners hope APOLLO program will be leap forward for precision oncology. US Department of Veteran Affairs. May 1, 2019. Accessed December 8, 2022. https://www.research.va.gov/currents/0519-VA-and-partners-hope-APOLLO-program-will-be-leap-forward-for-precision-oncology.cfm
  15. Konteatis Z et al. ACS Med Chem Lett. 2020;11(2):101-107. doi:10.1021/acsmedchemlett.9b00509
References
  1. Sokolov AV et al. Pharmacol Rev. 2021;73(4):1-32. doi:10.1124/pharmrev.121.000317
  2. Louis DN et al. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
  3. Mellinghoff IK et al. Clin Cancer Res. 2021;27(16):4491-4499. doi:10.1158/1078-0432.CCR-21-0611
  4. Woo C et al. JCO Clin Cancer Inform. 2021;5:985-994. doi:10.1200/CCI.21.00052
  5. Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO). ClinicalTrials.gov. Updated May 17, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04164901
  6. Servier's pivotal phase 3 indigo trial investigating vorasidenib in IDH-mutant low-grade glioma meets primary endpoint of progression-free survival (PFS) and key secondary endpoint of time to next intervention (TTNI) (no date) Servier US. March 14, 2023. Accessed March 20, 2023. https://www.servier.us/serviers-pivotal-phase-3-indigo-trial-meets-primary-endpoint
  7. Nehra M et al. J Control Release. 2021;338:224-243. doi:10.1016/j.jconrel.2021.08.027
  8. Hersh AM et al. Cancers (Basel). 2022;14(19):4920. doi:10.3390/cancers14194920
  9. Shoaf ML, Desjardins A. Neurotherapeutics. 2022;19(6):1818-1831. doi:10.1007/s13311-022-01256-1
  10. Bagley SJ, O’Rourke DM. Pharmacol Ther. 2020;205:107419. doi:10.1016/j.pharmthera.2019.107419
  11. Batich KA et al. Clin Cancer Res. 2020;26(20):5297-5303. doi:10.1158/1078-0432.CCR-20-1082
  12. Lin J et al. Cancer. 2020;126(13):3053-3060. doi:10.1002/cncr.32884
  13. Barth SK et al. Cancer Epidemiol. 2017;50(pt A):22-29. doi:10.1016/j.canep.2017.07.012
  14. VA and partners hope APOLLO program will be leap forward for precision oncology. US Department of Veteran Affairs. May 1, 2019. Accessed December 8, 2022. https://www.research.va.gov/currents/0519-VA-and-partners-hope-APOLLO-program-will-be-leap-forward-for-precision-oncology.cfm
  15. Konteatis Z et al. ACS Med Chem Lett. 2020;11(2):101-107. doi:10.1021/acsmedchemlett.9b00509
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Brain cancer remains a tremendous challenge in oncology, often with the worst prognosis and fewest approved treatment options.1 Classifying, treating, and identifying the causes in both the general population and in veterans have been challenging; but recently, there has been progress.2-4 In 2021, the World Health Organization (WHO) updated the classification system for primary brain and spinal cord tumors.2 Most importantly, the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) updates included the importance of molecular diagnostic techniques to ensure appropriate diagnoses.2 

Along with the progress in tumor classification, treatment advances are also showing promise with the use of new targeted therapies.3 A multi-site phase 3 clinical trial investigating an isocitrate dehydrogenase (IDH) inhibitor, vorasidenib, in patients with residual or recurrent IDH mutant low-grade glioma met its primary endpoint of PFS in March 2023.5,6 In addition to brain-penetrant targeted therapies, advances in drug administration and delivery have also emerged to circumvent the blood-brain barrier using nanotechnology, focused ultrasound, oncolytic viruses, vaccines, and CAR T-cell therapies.7-11

Many unanswered questions remain regarding the rates and outcomes for veterans with brain cancer. However, investigations and initiatives are ongoing to better understand the role of military service and exposures that may be associated with an increased risk of developing brain tumors.4,12,13 In addition, efforts are in place to improve molecular characterization and personalized treatments for brain cancer through the Applied Proteogenomics Organizational Learning and Outcomes (APOLLO) and NPOP.14 Despite the complexity of brain cancer, with its numerous challenges and unknowns, there have been recent advances in classification and potential treatments. Understanding the causes and improving treatments for brain cancer in the veteran population is paramount.

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