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

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Therapeutic Advances in Medical Oncology, Vol 14 (2022)
Druh dokumentu: article
ISSN: 1758-8359
17588359
DOI: 10.1177/17588359221141761
Popis: 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.
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