The Nail in the Coffin?: Examining the KEYNOTE-789 Clinical Trial's Impact

Zhaohui Liao Arter; Misako Nagasaka

doi:10.2147/LCTT.S443099

The Nail in the Coffin?: Examining the KEYNOTE-789 Clinical Trial's Impact

Lung Cancer (Auckl). 2024 Jan 25:15:1-8. doi: 10.2147/LCTT.S443099. eCollection 2024.

Authors

Zhaohui Liao Arter^{1

2}, Misako Nagasaka^{1

2

3}

Affiliations

¹ Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA, USA.
² Chao Family Comprehensive Cancer Center, Orange, CA, USA.
³ Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Abstract

Targeted therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), have revolutionized the treatment landscape for EGFR-mutant non-small cell lung cancer (NSCLC). However, the emergence of resistance to EGFR TKIs especially the third generation TKIs such as osimertinib remains a major clinical challenge. As a broader strategy for combating resistance, several clinical trials have explored the efficacy of immune checkpoint inhibitors (ICIs)+chemotherapy in EGFR-mutated NSCLC. Until now, the ORIENT-31 and IMpower150 trials suggested that ICIs+ chemotherapy may be more effective than chemotherapy alone after failure of EGFR-TKIs (although ORIENT-31 was negative for overall survival [OS] and IMpower150 was a subset analysis, so the study was not powered to detect a difference); however, the CheckMate-722 trial yielded disappointing results. Thus, the results of this global trial KEYNOTE-789 were highly anticipated.

Keywords: EGFR; chemo-immunotherapy; post-osimertinib; targeted therapy.

Grants and funding

No funding was received for this project.