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Plasma tumor mutation burden is associated with clinical benefit in patients with non-small cell lung cancer treated with anti-programmed death-1 monotherapy

Authors
 Jii Bum Lee  ;  Hyung Soon Park  ;  Su Jin Choi  ;  Seong Gu Heo  ;  Ho Jung An  ;  Hye Ryun Kim  ;  Min Hee Hong  ;  Sun Min Lim  ;  Kyle Chang  ;  Katie Quinn  ;  Justin Odegaard  ;  Byoung Yong Shim  ;  Byoung Chul Cho 
Citation
 THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, Vol.14 : 17588359221141761, 2022-12 
Journal Title
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
ISSN
 1758-8340 
Issue Date
2022-12
Keywords
anti-PD-1 ; clinical benefit ; genetic alterations ; non-small cell lung cancer ; plasma tumor mutational burden
Abstract
Background: The clinical utility of plasma tumor mutational burden (pTMB) requires further validation. Herein, the pTMB and genetic alterations were investigated as predictive biomarkers for anti-PD-1 monotherapy outcome in metastatic non-small cell lung cancer (NSCLC).

Methods: The GuardantOMNI panel (Guardant Health) was used to identify pTMB and genetic alterations. Data from 99 patients with metastatic NSCLC treated with pembrolizumab or nivolumab in first-, second-, or third-line settings between June 2016 and December 2020 were collected. Associations between pTMB and clinical benefit rate (CBR, stable disease ⩾6 months or partial response), progression-free survival (PFS), and overall survival (OS) were assessed.

Results: Median pTMB in 84 patients was 10.8 mutations/megabase (mut/Mb). Histological analyses revealed that 61 and 36% of the patients had adenocarcinomas and squamous NSCLC, respectively. Most patients were treated with nivolumab (74%) and most anti-PD-1 agents were administered as second-line treatment (70%). The median follow-up duration was of 10.9 months (range, 0.2-40.7). Patients with high pTMB (⩾19 mut/Mb) had a higher CBR (69%) compared with low pTMB patients (33%; p = 0.01). ARID1A (p = 0.007) and either ERBB2 or KIT mutations (p = 0.012) were positive and negative determinants, respectively, for clinical benefit. Multivariate analysis further showed that high pTMB was an independent predictive biomarker for both PFS [hazard ratio (HR) = 0.44, 95% confidence interval (CI): 0.22-0.88, p = 0.02] and OS (HR = 0.37, 95% CI: 0.18-0.76, p = 0.007).

Conclusion: High pTMB (⩾19 mut/Mb) is significantly associated with CBR in patients with NSCLC treated with anti-PD-1 agents.
Files in This Item:
T9992022870.pdf Download
DOI
10.1177/17588359221141761
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Lim, Sun Min(임선민)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193976
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