ECB-ART-51866
Nat Med
2022 Nov 01;2811:2353-2363. doi: 10.1038/s41591-022-02047-z.
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Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer.
Jee J
,
Lebow ES
,
Yeh R
,
Das JP
,
Namakydoust A
,
Paik PK
,
Chaft JE
,
Jayakumaran G
,
Rose Brannon A
,
Benayed R
,
Zehir A
,
Donoghue M
,
Schultz N
,
Chakravarty D
,
Kundra R
,
Madupuri R
,
Murciano-Goroff YR
,
Tu HY
,
Xu CR
,
Martinez A
,
Wilhelm C
,
Galle J
,
Daly B
,
Yu HA
,
Offin M
,
Hellmann MD
,
Lito P
,
Arbour KC
,
Zauderer MG
,
Kris MG
,
Ng KK
,
Eng J
,
Preeshagul I
,
Victoria Lai W
,
Fiore JJ
,
Iqbal A
,
Molena D
,
Rocco G
,
Park BJ
,
Lim LP
,
Li M
,
Tong-Li C
,
De Silva M
,
Chan DL
,
Diakos CI
,
Itchins M
,
Clarke S
,
Pavlakis N
,
Lee A
,
Rekhtman N
,
Chang J
,
Travis WD
,
Riely GJ
,
Solit DB
,
Gonen M
,
Rusch VW
,
Rimner A
,
Gomez D
,
Drilon A
,
Scher HI
,
Shah SP
,
Berger MF
,
Arcila ME
,
Ladanyi M
,
Levine RL
,
Shen R
,
Razavi P
,
Reis-Filho JS
,
Jones DR
,
Rudin CM
,
Isbell JM
,
Li BT
.
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.
PubMed ID: 36357680
Article link: Nat Med
Grant support: [+]
P30 CA008748 NCI NIH HHS , T32 CA009207 NCI NIH HHS , UL1 TR000457 NCATS NIH HHS , P50 CA247749 NCI NIH HHS , R01 CA279264 NCI NIH HHS , R01 CA230267 NCI NIH HHS , R01 CA230745 NCI NIH HHS , P01 CA129243 NCI NIH HHS
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