Atezolizumab prolongs overall survival over docetaxel in advanced non-small-cell lung cancer patients harboring STK11 or KEAP1 mutation

Wei Nie, Lu Gan, Xin Wang, Kai Gu, Fang Fei Qian, Min Juan Hu, Ding Zhang, Shi Qing Chen, Jun Lu, Shu Hui Cao, Jing Wen Li, Yue Wang, Bo Zhang, Shu Yuan Wang, Chang Hui Li, Ping Yang, Mi–Die Xu, Xue Yan Zhang, Hua Zhong, Bao Hui Han

Research output: Contribution to journalArticlepeer-review

Abstract

Somatic mutations of STK11 or KEAP1 are associated with poor clinical outcomes for advanced non-small-cell lung cancer (aNSCLC) patients receiving immune checkpoint inhibitors (ICIs), chemotherapy, or targeted therapy. Which treatment regimens work better for STK11 or KEAP1 mutated (SKmut) aNSCLC patients is unknown. In this study, the efficacy of atezolizumab versus docetaxel in SKmut aNSCLC was compared. A total of 157 SKmut aNSCLC patients were identified from POPLAR and OAK trials, who were tested by blood-based FoundationOne next-generation sequencing assay. Detailed clinical data and genetic alterations were collected. Two independent cohorts were used for biomarker validation (n = 30 and 20, respectively). Median overall survival was 7.3 months (95% confidence interval [CI], 4.8 to 9.9) in the atezolizumab group versus 5.8 months (95% CI, 4.4 to 7.2) in the docetaxel group (adjusted hazard ratio [HR] for death, 0.70; 95% CI, 0.49 to 0.99; P = .042). Among atezolizumab-treated patients, objective response rate, disease control rate, and durable clinical benefit were higher when blood tumor mutation burden (bTMB) and PD-L1 being higher (biomarker 1, n = 61) or with FAT3 mutation-positive tumors (biomarker 2, n = 83) than otherwise. The interactions for survival between these two biomarkers and treatments were significant, which were further validated in two independent cohorts. In SKmut patients with aNSCLC, atezolizumab was associated with significantly longer overall survival in comparison to docetaxel. Having FAT3 mutation or high TMB and PD-L1 expression potentially predict favorable response in SKmut patients receiving atezolizumab.

Original languageEnglish (US)
Article number1865670
JournalOncoImmunology
Volume10
Issue number1
DOIs
StatePublished - 2021

Keywords

  • KEAP1
  • NSCLC
  • STK11
  • immune checkpoint inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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