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

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Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer
Nature Medicine ( IF 58.7 ) Pub Date : 2022-11-10 , DOI: 10.1038/s41591-022-02047-z
Justin Jee ₁ , Emily S Lebow ₁ , Randy Yeh ₁ , Jeeban P Das ₁ , Azadeh Namakydoust ₁ , Paul K Paik _{1,

2} , Jamie E Chaft _{1,

2} , Gowtham Jayakumaran ₁ , A Rose Brannon ₁ , Ryma Benayed ₁ , Ahmet Zehir ₁ , Mark Donoghue ₁ , Nikolaus Schultz ₁ , Debyani Chakravarty ₁ , Ritika Kundra ₁ , Ramyasree Madupuri ₁ , Yonina R Murciano-Goroff ₁ , Hai-Yan Tu _{1,

3} , Chong-Rui Xu _{1,

3} , Andrés Martinez ₁ , Clare Wilhelm ₁ , Jesse Galle ₁ , Bobby Daly _{1,

2} , Helena A Yu _{1,

2} , Michael Offin _{1,

2} , Matthew D Hellmann _{1,

2} , Piro Lito _{1,

2} , Kathryn C Arbour _{1,

2} , Marjorie G Zauderer _{1,

2} , Mark G Kris _{1,

2} , Kenneth K Ng _{1,

2} , Juliana Eng _{1,

2} , Isabel Preeshagul _{1,

2} , W Victoria Lai _{1,

2} , John J Fiore _{1,

2} , Afsheen Iqbal _{1,

2} , Daniela Molena _{1,

2} , Gaetano Rocco _{1,

2} , Bernard J Park _{1,

2} , Lee P Lim ₄ , Mark Li ₄ , Candace Tong-Li _{5,

6} , Madhawa De Silva ₅ , David L Chan ₅ , Connie I Diakos ₅ , Malinda Itchins ₅ , Stephen Clarke ₅ , Nick Pavlakis ₅ , Adrian Lee ₅ , Natasha Rekhtman _{1,

2} , Jason Chang _{1,

2} , William D Travis _{1,

2} , Gregory J Riely _{1,

2} , David B Solit _{1,

2} , Mithat Gonen ₁ , Valerie W Rusch _{1,

2} , Andreas Rimner _{1,

2} , Daniel Gomez _{1,

2} , Alexander Drilon _{1,

2} , Howard I Scher _{1,

2} , Sohrab P Shah ₁ , Michael F Berger ₁ , Maria E Arcila _{1,

2} , Marc Ladanyi _{1,

2} , Ross L Levine _{1,

2} , Ronglai Shen ₁ , Pedram Razavi _{1,

2} , Jorge S Reis-Filho _{1,

2} , David R Jones _{1,

2} , Charles M Rudin _{1,

2} , James M Isbell _{1,

2} , Bob T Li _{1,

2}

Affiliation

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.

中文翻译：

循环肿瘤 DNA 引导治疗晚期非小细胞肺癌的总体生存率

循环肿瘤 DNA (ctDNA) 测序可指导治疗决策，但主要在小规模队列中进行研究，没有足够的随访来确定其对总体生存的影响。我们前瞻性地跟踪了一个由 1,127 名接受 ctDNA 指导治疗的非小细胞肺癌患者组成的国际队列。 ctDNA 检测与较短的生存期相关（风险比 (HR)，2.05；95% 置信区间 (CI)，1.74–2.42； P < 0.001），与临床病理特征和代谢肿瘤体积无关。在 722 名 (64%) 具有可检测 ctDNA 的患者中，255 名 (23%) 通过 ctDNA 测序匹配靶向治疗的患者比未接受靶向治疗的患者生存期更长（HR，0.63；95% CI，0.52-0.76； P < 0.001 ）。在 25% 的患者中发现了时间匹配的组织测序未检测到的 ctDNA 基因组改变。这些仅 ctDNA 的改变不成比例地具有亚克隆耐药驱动因素，包括RICTOR和PIK3CA改变，并且与短生存期相关。微创 ctDNA 分析可以识别组织测序中未捕获的异质驱动因素，并扩大社区获得延长生命治疗的机会。

更新日期：2022-11-10

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