Synapse - Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer

Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer Journal Article

Authors:	Jee, J.; Lebow, E. S.; Yeh, R.; Das, J. P.; Namakydoust, A.; Paik, P. K.; Chaft, J. E.; Jayakumaran, G.; Brannon, A. R.; Benayed, R.; Zehir, A.; Donoghue, M.; Schultz, N.; Chakravarty, D.; Kundra, R.; Madupuri, R.; Murciano-Goroff, Y. R.; Tu, H. Y.; Xu, C. R.; Martinez, A.; Wilhelm, C.; Galle, J.; Daly, B.; Yu, H. A.; Offin, M.; Hellmann, M. D.; Lito, P.; Arbour, K. C.; Zauderer, M. G.; Kris, M. G.; Ng, K. K.; Eng, J.; Preeshagul, I.; Lai, W. V.; Fiore, J. J.; Iqbal, A.; Molena, D.; Rocco, G.; Park, B. J.; Lim, L. P.; Li, M.; Tong-Li, C.; De Silva, M.; Chan, D. L.; Diakos, C. I.; Itchins, M.; Clarke, S.; Pavlakis, N.; Lee, A.; Rekhtman, N.; Chang, J.; Travis, W. D.; Riely, G. J.; Solit, D. B.; Gonen, M.; Rusch, V. W.; Rimner, A.; Gomez, D.; Drilon, A.; Scher, H. I.; Shah, S. P.; Berger, M. F.; Arcila, M. E.; Ladanyi, M.; Levine, R. L.; Shen, R.; Razavi, P.; Reis-Filho, J. S.; Jones, D. R.; Rudin, C. M.; Isbell, J. M.; Li, B. T.
Article Title:	Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer
Abstract:	Circulating tumor DNA (ctDNA) sequencing guides therapy decisions but has been studied mostly in small cohorts without sufficient follow-up to determine its influence on overall survival. We prospectively followed an international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy. ctDNA detection was associated with shorter survival (hazard ratio (HR), 2.05; 95% confidence interval (CI), 1.74–2.42; P < 0.001) independently of clinicopathologic features and metabolic tumor volume. Among the 722 (64%) patients with detectable ctDNA, 255 (23%) matched to targeted therapy by ctDNA sequencing had longer survival than those not treated with targeted therapy (HR, 0.63; 95% CI, 0.52–0.76; P < 0.001). Genomic alterations in ctDNA not detected by time-matched tissue sequencing were found in 25% of the patients. These ctDNA-only alterations disproportionately featured subclonal drivers of resistance, including RICTOR and PIK3CA alterations, and were associated with short survival. Minimally invasive ctDNA profiling can identify heterogeneous drivers not captured in tissue sequencing and expand community access to life-prolonging therapy. © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords:	genetics; mutation; carcinoma, non-small-cell lung; lung neoplasms; tumor marker; lung tumor; non small cell lung cancer; high throughput sequencing; high-throughput nucleotide sequencing; humans; human; circulating tumor dna; biomarkers, tumor
Journal Title:	Nature Medicine
Volume:	28
Issue:	11
ISSN:	1078-8956
Publisher:	Nature Publishing Group
Date Published:	2022-11-01
Start Page:	2353
End Page:	2363
Language:	English
DOI:	10.1038/s41591-022-02047-z
PUBMED:	36357680
PROVIDER:	scopus
PMCID:	PMC10338177
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141677358&doi=10.1038%2fs41591-022-02047-z&partnerID=40&md5=f33dc545030638f7436d5282a07022b5
Notes:	Article -- Export Date: 1 December 2022 -- Source: Scopus