Lung Cancer: Targets and Therapy (Jan 2024)
The Nail in the Coffin?: Examining the KEYNOTE-789 Clinical Trial’s Impact
Abstract
Zhaohui Liao Arter,1,2 Misako Nagasaka1– 3 1Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA, USA; 2Chao Family Comprehensive Cancer Center, Orange, CA, USA; 3Department of Medicine, St. Marianna University School of Medicine, Kawasaki, JapanCorrespondence: Misako Nagasaka, Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, Orange, CA, 92602, USA, Email [email protected]: 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, post-osimertinib, chemo-immunotherapy, targeted therapy
