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

被引：102

作者：

Jee, Justin ^{[1
]}

Lebow, Emily S. ^{[1
]}

Yeh, Randy ^{[1
]}

Das, Jeeban P. ^{[1
]}

Namakydoust, Azadeh ^{[1
]}

Paik, Paul K. ^{[1
,2
]}

Chaft, Jamie E. ^{[1
,2
]}

Jayakumaran, Gowtham ^{[1
]}

Brannon, A. Rose ^{[1
]}

Benayed, Ryma ^{[1
]}

Zehir, Ahmet ^{[1
]}

Donoghue, Mark ^{[1
]}

Schultz, Nikolaus ^{[1
]}

Chakravarty, Debyani ^{[1
]}

Kundra, Ritika ^{[1
]}

Madupuri, Ramyasree ^{[1
]}

Murciano-Goroff, Yonina R. ^{[1
]}

Tu, Hai-Yan ^{[1
,3
,4
]}

Xu, Chong-Rui ^{[1
,3
,4
]}

Martinez, Andres ^{[1
]}

Wilhelm, Clare ^{[1
]}

Galle, Jesse ^{[1
]}

Daly, Bobby ^{[1
,2
]}

Yu, Helena A. ^{[1
,2
]}

Offin, Michael ^{[1
,2
]}

Hellmann, Matthew D. ^{[1
,2
]}

Lito, Piro ^{[1
,2
]}

Arbour, Kathryn C. ^{[1
,2
]}

Zauderer, Marjorie G. ^{[1
,2
]}

Kris, Mark G. ^{[1
,2
]}

Ng, Kenneth K. ^{[1
,2
]}

Eng, Juliana ^{[1
,2
]}

Preeshagul, Isabel ^{[1
,2
]}

Lai, W. Victoria ^{[1
,2
]}

Fiore, John J. ^{[1
,2
]}

Iqbal, Afsheen ^{[1
,2
]}

Molena, Daniela ^{[1
,2
]}

Rocco, Gaetano ^{[1
,2
]}

Park, Bernard J. ^{[1
,2
]}

Lim, Lee P. ^{[5
]}

Li, Mark ^{[5
]}

Tong-Li, Candace ^{[6
,7
]}

De Silva, Madhawa ^{[6
]}

Chan, David L. ^{[6
]}

Diakos, Connie, I ^{[6
]}

Itchins, Malinda ^{[6
]}

Clarke, Stephen ^{[6
]}

Pavlakis, Nick ^{[6
]}

Lee, Adrian ^{[6
]}

Rekhtman, Natasha ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[2] Cornell Univ, Weill Cornell Med, New York, NY 10021 USA

[3] Guangdong Prov Peoples Hosp, Guangdong Lung Canc Inst, Guangzhou, Peoples R China

[4] Guangdong Acad Med Sci, Guangzhou, Peoples R China

[5] Agilent Technol, Resolut Biosci, Kirkland, WA USA

[6] Univ Sydney, GenesisCare, Sydney, NSW, Australia

[7] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA

来源：

NATURE MEDICINE | 2022年 / 28卷 / 11期

基金：

美国国家卫生研究院;

关键词：

CLINICAL-TRIALS; LIQUID BIOPSY; EGFR; ASSOCIATION; RESISTANCE; EVOLUTION; ONCOLOGY; MUTATION; UTILITY; ASSAYS;

D O I：

10.1038/s41591-022-02047-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. 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.

引用

页码：2353 / +

页数：21

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