PMID- 36846007
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230228
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 11
IP  - 3
DP  - 2023 Feb 15
TI  - The efficacy and safety of PD-1 inhibitors for EGFR-mutant non-small cell lung 
      cancer after tyrosine kinase inhibitor failure: a retrospective real-world cohort 
      study.
PG  - 157
LID - 10.21037/atm-22-6272 [doi]
LID - 157
AB  - BACKGROUND: Acquired drug resistance to various tyrosine kinase inhibitor (TKI) 
      inevitably develops in almost all epidermal growth factor receptor (EGFR)-mutant 
      non-small cell lung cancer (NSCLC). The present study aimed to evaluate the 
      efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors for such 
      patients after TKI failure and further explore the subpopulation that exhibited 
      the most benefit. METHODS: A total of 102 EGFR-mutant NSCLC patients who received 
      PD-1 inhibitors after developing resistance to EGFR-TKIs were included in the 
      study. The primary endpoints were progression-free survival (PFS) and grade 3-5 
      adverse events (AEs), while the secondary endpoints were overall survival (OS), 
      disease control rate (DCR) and subgroup analyses. RESULTS: All the 102 patients 
      received 2 or more lines of immunotherapy. The overall median PFS was 4.95 months 
      [95% confidence interval (CI): 3.91-5.89 months]. The EGFR(L858R) group showed a 
      significant PFS benefit compared with the EGFR(D19) group (6.4 vs. 3.5 months, 
      P=0.002), and likewise for the DCR between the 2 groups (EGFR(L858R) vs. 
      EGFR(D19) group: 84.3% vs. 66.7%, P=0.049). In addition, median PFS in the 
      EGFR(T790M)-negative group (6.47 months) was significantly longer than the 
      EGFR(T790M)-positive group (3.20 months) (P=0.003). The overall OS was 10.70 
      months (95% CI: 8.92-12.48 months), without a prognostic factor. There was a 
      trend towards improved PFS and OS with combination therapy. The incidence of 
      grade 3-5 treatment-related AEs was 19.6%, while the incidence of grade 3-5 
      immune-related AEs (irAEs) was 6.9%. Treatment-related AEs were similar in 
      different mutation subtypes. The incidence of grade 3-5 irAEs was higher in the 
      EGFR(D19) group (10.3%) compared with the EGFR(L858R) group (5.9%), and likewise 
      in the EGFR(T790M)-negative group (10%) compared with the EGFR(T790M)-positive 
      group (2.6%). CONCLUSIONS: After EGFR-TKI failure, PD-1 inhibitors provided 
      better survival in advanced NSCLC for the EGFR(L858R) subgroup and 
      EGFR(T790M)-negative subgroup, and there was a trend towards improved outcomes 
      with combination therapy. In addition, toxicity was well tolerated. Our 
      real-world study increased the population size and obtained a similar survival 
      outcome compared from clinical trials.
CI  - 2023 Annals of Translational Medicine. All rights reserved.
FAU - Zhou, Chunyang
AU  - Zhou C
AD  - Department of Radiation Oncology, Qilu Hospital (Qingdao), Cheeloo College of 
      Medicine, Shandong University, Qingdao, China.
FAU - Wang, Zijian
AU  - Wang Z
AD  - College of Traditional Chinese Medicine, Shandong University of Traditional 
      Chinese Medicine, Jinan, China.
FAU - Fu, Chengrui
AU  - Fu C
AD  - Department of Radiation Oncology, Shandong Cancer Hospital and Institute, 
      Shandong First Medical University and Shandong Academy of Medical Sciences, 
      China.
FAU - Tao, Hengmin
AU  - Tao H
AD  - Department of Head and Neck Radiotherapy, Shandong Provincial ENT Hospital, 
      Shandong University, Jinan, China.
FAU - Liu, Chengxin
AU  - Liu C
AD  - Department of Radiation Oncology, Shandong Cancer Hospital and Institute, 
      Shandong First Medical University and Shandong Academy of Medical Sciences, 
      China.
AD  - Cheeloo College of Medicine, Shandong University, Jinan, China.
LA  - eng
PT  - Journal Article
DEP - 20230210
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC9951015
OTO - NOTNLM
OT  - Epidermal growth factor receptor (EGFR)
OT  - immune checkpoint inhibitors (ICIs)
OT  - immune combined therapy
OT  - non-small cell lung cancer (NSCLC)
OT  - programmed death-ligand 1 (PD-L1)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://atm.amegroups.com/article/view/10.21037/atm-22-6272/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2023/02/28 06:00
MHDA- 2023/02/28 06:01
PMCR- 2023/02/15
CRDT- 2023/02/27 05:30
PHST- 2022/11/28 00:00 [received]
PHST- 2023/01/29 00:00 [accepted]
PHST- 2023/02/27 05:30 [entrez]
PHST- 2023/02/28 06:00 [pubmed]
PHST- 2023/02/28 06:01 [medline]
PHST- 2023/02/15 00:00 [pmc-release]
AID - atm-11-03-157 [pii]
AID - 10.21037/atm-22-6272 [doi]
PST - ppublish
SO  - Ann Transl Med. 2023 Feb 15;11(3):157. doi: 10.21037/atm-22-6272. Epub 2023 Feb 
      10.