학술논문
Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer
Document Type
Original Paper
Author
Jee, Justin; Lebow, Emily S.; Yeh, Randy; Das, Jeeban P.; Namakydoust, Azadeh; Paik, Paul K.; Chaft, Jamie E.; Jayakumaran, Gowtham; Rose Brannon, A.; Benayed, Ryma; Zehir, Ahmet; Donoghue, Mark; Schultz, Nikolaus; Chakravarty, Debyani; Kundra, Ritika; Madupuri, Ramyasree; Murciano-Goroff, Yonina R.; Tu, Hai-Yan; Xu, Chong-Rui; Martinez, Andrés; Wilhelm, Clare; Galle, Jesse; Daly, Bobby; Yu, Helena A.; Offin, Michael; Hellmann, Matthew D.; Lito, Piro; Arbour, Kathryn C.; Zauderer, Marjorie G.; Kris, Mark G.; Ng, Kenneth K.; Eng, Juliana; Preeshagul, Isabel; Victoria Lai, W.; Fiore, John J.; Iqbal, Afsheen; Molena, Daniela; Rocco, Gaetano; Park, Bernard J.; Lim, Lee P.; Li, Mark; Tong-Li, Candace; De Silva, Madhawa; Chan, David L.; Diakos, Connie I.; Itchins, Malinda; Clarke, Stephen; Pavlakis, Nick; Lee, Adrian; Rekhtman, Natasha; Chang, Jason; Travis, William D.; Riely, Gregory J.; Solit, David B.; Gonen, Mithat; Rusch, Valerie W.; Rimner, Andreas; Gomez, Daniel; Drilon, Alexander; Scher, Howard I.; Shah, Sohrab P.; Berger, Michael F.; Arcila, Maria E.; Ladanyi, Marc; Levine, Ross L.; Shen, Ronglai; Razavi, Pedram; Reis-Filho, Jorge S.; Jones, David R.; Rudin, Charles M.; Isbell, James M.; Li, Bob T.
Source
Nature Medicine. 28(11):2353-2363
Subject
Language
English
ISSN
1078-8956
1546-170X
1546-170X
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.
In a prospective international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy, ctDNA detection was associated with shorter survival, independently of clinicopathologic features and metabolic tumor volume.
In a prospective international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy, ctDNA detection was associated with shorter survival, independently of clinicopathologic features and metabolic tumor volume.