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Survival analysis for non-squamous NSCLC patients harbored STK11 or KEAP1 mutation receiving atezolizumab

Xiaoling Shang1, Zhenxiang Li2, Jian Sun3

  • 1Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China; Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.

Lung Cancer (Amsterdam, Netherlands)
|February 28, 2021
PubMed
Abstract

Insights

STK11/KEAP1 mutations in non-squamous non-small cell lung cancer (NSCLC) patients were associated with worse survival outcomes with atezolizumab and docetaxel. Patients with KEAP1 mutations may benefit more from atezolizumab than docetaxel.

Area of Science:

  • Oncology
  • Genomics
  • Medical Diagnostics

Background:

  • STK11 and KEAP1 mutations are prevalent in non-small cell lung cancer (NSCLC).
  • The prognostic impact of these mutations on treatment outcomes with atezolizumab and docetaxel requires further investigation.

Purpose of the Study:

  • To analyze the prognostic effect of STK11/KEAP1 mutations in patients with non-squamous NSCLC receiving atezolizumab and docetaxel.
  • To explore the correlation between STK11/KEAP1 mutations, blood-based tumor mutational burden (bTMB), and PD-L1 expression.

Main Methods:

  • Utilized data from OAK and POPLAR clinical trials.
  • Analyzed genomic alteration frequency, bTMB, and PD-L1 expression.
  • Employed Cox regression, Kaplan-Meier, and log-rank tests for survival analysis.

Main Results:

  • STK11/KEAP1 mutations were found in 7.33%/10.76% of non-squamous NSCLC.
  • Patients with STK11/KEAP1 mutations exhibited higher bTMB.
  • STK11/KEAP1 mutations were independent prognostic factors for overall survival (OS) and progression-free survival (PFS).
  • Patients with STK11/KEAP1 mutations had worse OS with both treatments.
  • Atezolizumab showed improved survival over docetaxel for KEAP1-mutated, STK11 wild-type NSCLC patients.

Conclusions:

  • Non-squamous NSCLC patients with STK11/KEAP1 mutations may not derive significant benefit from atezolizumab or docetaxel.
  • Patients with KEAP1 mutations alone may respond better to atezolizumab compared to docetaxel.
Keywords:
AtezolizumabKEAP1 mutationNon-squamous NSCLCSTK11 mutationSurvival

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