Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor-Based Immunotherapy.
Yulian Khagi,Aaron M. Goodman,Gregory A. Daniels,Sandip Pravin Patel,Assuntina G. Sacco,James Michael Randall,Lyudmila Bazhenova,Razelle Kurzrock +7 more
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TLDR
Given the association of alteration number on liquid biopsy and checkpoint inhibitor–based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted.Abstract:
Purpose: Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response.Experimental Design: We assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived ctDNA NGS testing (54-70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations.Results: Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, >3 alterations versus VUS ≤3 alterations), SD ≥6 months/PR/CR 45% versus 15%, respectively; P = 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 vs. 3 had a median PFS of 23 versus 2.3 months (P = 0.0004).Conclusions: Given the association of alteration number on liquid biopsy and checkpoint inhibitor-based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted. Clin Cancer Res; 23(19); 5729-36. ©2017 AACR.read more
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The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy
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Current and future perspectives of liquid biopsies in genomics-driven oncology.
TL;DR: The potential of liquid biopsies is highlighted by studies that show they can track the evolutionary dynamics and heterogeneity of tumours and can detect very early emergence of therapy resistance, residual disease and recurrence, but their analytical validity and clinical utility must be rigorously demonstrated before this potential can be realized.
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Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC
Christian Rolfo,Philip C. Mack,Giorgio V. Scagliotti,Paul Baas,Fabrice Barlesi,Trever G. Bivona,Roy S. Herbst,Tony Mok,Nir Peled,Robert Pirker,Luis E. Raez,Martin Reck,Jonathan W. Riess,Lecia V. Sequist,Frances A. Shepherd,Lynette M. Sholl,Daniel Shao-Weng Tan,Heather A. Wakelee,Ignacio I. Wistuba,Murry W. Wynes,David P. Carbone,Fred R. Hirsch,David R. Gandara +22 more
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Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Patients With Non-Small Cell Lung Cancer With Use of a Next-Generation Sequencing Cancer Gene Panel.
Zhijie Wang,Jianchun Duan,Shangli Cai,Miao Han,Hua Dong,Jun Zhao,Bo Zhu,Shuhang Wang,Minglei Zhuo,Jianguo Sun,Qiming Wang,Hua Bai,Jiefei Han,Yanhua Tian,Jing Lu,Tongfu Xu,Xiaochen Zhao,Guoqiang Wang,Xinkai Cao,Fugen Li,Dalei Wang,Chen Yuejun,Yuezong Bai,Jing Zhao,Zhengyi Zhao,Yuzi Zhang,Lei Xiong,Jie He,Shugeng Gao,Jie Wang +29 more
TL;DR: The findings suggest that established NCC-GP150 with an optimized gene panel size and algorithm is feasible for bTMB estimation, which may serve as a potential biomarker of clinical benefit in patients with NSCLC treated with anti–PD-1 and anti-PD-L1 agents.
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Pembrolizumab for the treatment of non-small cell lung cancer
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TL;DR: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer and PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolIZumab.
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