Genomic Landscape- Finding the Fusion
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precision

Precision oncology provides a unique opportunity to improve clinical outcomes1

Benefits of precision oncology

From 2006 to 2018, there was a 7x increase in the number of patients estimated to benefit from genome-based therapy2

Precision oncology benefits
  • Significant improvements in ORR, PFS, and QOL for certain well-characterized molecular alterations with available targeted therapies compared with conventional chemotherapies3-5
  • Potentially avoids cycles of trial and error and associated adverse physical and financial impact6
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aWhen adjusted for age, sex, histologic diagnosis, and number of previous lines of treatment.7

The data-driven difference

Targeting genomic alterations can potentially lead to better outcomes for patients1

OS in NSCLC with targeted vs nontargeted therapy8
OS in NSCLC With Targeted Therapy and OS in Pancreatic Cancer With Matched vs Unmatched Therapy
OS in pancreatic cancer with matched vs unmatched therapy9
OS in NSCLC With Targeted Therapy and OS in Pancreatic Cancer With Matched vs Unmatched Therapy
In both studies, OS was significantly longer in patients who received therapies directed toward their specific alterations.8,9

Key genomic alterations

Point mutations and pathogenic gene fusions are among the most common genomic alterations driving cancer10

Point mutations
Point mutations
(eg, KRAS, BRAF, and EGFR) are changes in DNA base pair(s)11,12
Pathogenic gene fusions
Pathogenic gene fusions
(eg, ALK, NTRK, ROS1, MET, and NRG1) typically occur when 2 different genes join to form an abnormal hybrid gene12-14
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Pathogenic Gene Fusion

Gene Fusion Iconarrow
Fusion protein Selected
Oncogenic fusion protein
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Cancer Selected
Cancer

Point Mutation

Point Mutation Iconarrow
Protein Unselected
Oncogenic protein
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Cancer Selected
Cancer
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Point Mutation
Pathogenic Gene Fusion
Point Mutation Icon
What difference can targeting pathogenic gene fusions make for your patients?
See the datanext page
HR, hazard ratio; IQR, interquartile range; NSCLC, non–small cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; QOL, quality of life.
References: 1. Zhao S, Zhang Z, Zhan J, et al. Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer. BMC Med. 2021;19(1):223. doi:10.1186/s12916-021-02089-z 2. Marquart J, Chen EY, Prasad V. Estimation of the percentage of US patients with cancer who benefit from genome-driven oncology. JAMA Oncol. 2018;4(8):1093-1098. doi:10.1001/jamaoncol.2018.1660 3. Shin DH, Lee D, Hong DW, et al. Oncogenic function and clinical implications of SLC3A2-NRG1 fusion in invasive mucinous adenocarcinoma of the lung. Oncotarget. 2016;7(43):69450-69465. doi:10.18632/oncotarget.11913 4. Doroshow DB, Doroshow JH. Genomics and the history of precision oncology. Surg Oncol Clin N Am. 2020;29(1):35-49. doi:10.1016/j.soc.2019.08.003 5. Lassen UN, Makaroff LE, Stenzinger A, et al. Precision oncology: a clinical and patient perspective. Future Oncol. 2021;17(30):3995-4009. doi:10.2217/fon-2021-0688 6. Personalized Medicine Coalition. The Personalized Medicine Report 2020: Opportunities, Challenges, and the Future. Accessed February 7, 2023. www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/PMC_The_Personalized_Medicine_Report_Opportunity_Challenges_and_the_Future.pdf 7. Haslem DS, Van Norman SB, Fulde G, et al. A retrospective analysis of precision medicine outcomes in patients with advanced cancer reveals improved progression-free survival without increased health care costs. J Oncol Pract. 2017;13(2):e108-e119. doi:10.1200/JOP.2016.011486 8. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. doi:10.1001/jama.2014.3741 9. Pishvaian MJ, Blais EM, Brody JR, et al. Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial. Lancet Oncol. 2020;21(4):508-518. doi:10.1016/S1470-2045(20)30074-7 10. Zhang R, Dong L, Yu J. Concomitant pathogenic mutations and fusions of driver oncogenes in tumors. Front Oncol. 2021;10:544579. doi:10.3389/fonc.2020.544579 11. Gunter C. Point mutation. National Human Genome Research Institute. Updated February 3, 2023. Accessed February 7, 2023. https://www.genome.gov/genetics-glossary/Point-Mutation 12. Malone ER, Oliva M, Sabatini PJB, Stockley TL, Siu LL. Molecular profiling for precision cancer therapies. Genome Med. 2020;12(1):8. doi:10.1186/s13073-019-0703-1 13. Drilon A, Duruisseaux M, Han J-Y, et al. Clinicopathologic features and response to therapy of NRG1 fusion–driven lung cancers: the eNRGy1 Global Multicenter Registry. J Clin Oncol. 2021;39(25):2791-2802. doi:10.1200/JCO.20.03307 14. Latysheva NS, Babu MM. Discovering and understanding oncogenic gene fusions through data intensive computational approaches. Nucleic Acids Res. 2016;44(10):4487-4503. doi:10.1093/nar/gkw282