PMID- 38379896
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240222
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 15
DP  - 2024
TI  - A meta-analysis of the efficacy of programmed cell death 1/its ligand inhibitors 
      plus cytotoxic T-lymphocyte-associated antigen 4 inhibitors in non-small cell 
      lung cancer.
PG  - 1267763
LID - 10.3389/fphar.2024.1267763 [doi]
LID - 1267763
AB  - Background: Immune checkpoint inhibitors (ICIs), either as monotherapy or in 
      combination with chemotherapy, have improved the therapeutic outcome for 
      non-small cell lung cancer (NSCLC). However, the efficacy of combination 
      therapies, such as programmed cell death 1(PD-1)/its ligand (PD-L1) and cytotoxic 
      T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, in targeting different 
      pathways remains unclear. We performed a meta-analysis to determine whether the 
      addition of a CTLA-4 inhibitor to PD-1/PD-L1 therapy improves the efficacy of 
      PD-1/PD-L1 monotherapy in NSCLC. Methods: We systematically searched various 
      electronic databases for suitable trials. Only randomized controlled trials 
      (RCTs) comparing the clinical efficacy of PD-1/PD-L1 with and without CTLA-4 were 
      included in the analyses. The meta-analysis software RevMan 5.3 was used for 
      statistical analyses. Results: A total of seven RCTs were retrieved. The results 
      suggested that the combination of CTLA-4 and PD-1/PDL-1 inhibitors did not show 
      enhanced efficacy over PD1/PDL-1 inhibitor monotherapy as determined by overall 
      survival (OS) (HR = 0.98, 95% CI = 0.84-1.14, p = 0.79), progression-free 
      survival (PFS) (HR = 0.92, 95% CI = 0.81-1.06, p = 0.25), and objective response 
      rate (ORR) (HR = 1.08, 95% CI = 0.96-1.21, p = 0.19). Furthermore, the 
      combination immunotherapy was associated increased toxicity as evidenced by 
      increased incidence of any type adverse events (AEs) (RR = 1.06, 95% CI = 
      1.00-1.13, p = 0.03), grade >/=3 immune-mediated AEs (RR = 1.58, 95% CI = 
      1.36-1.82, p < 0.05), and treatment discontinuation (RR = 1.83, 95% CI = 
      1.46-2.28, p < 0.05). Conclusion: Combining anti-CTLA-4 with anti-PD-1/PD-L1 
      therapy did not improve the therapeutic efficacy, and was associated with greater 
      toxicity than anti-PD-1/PD-L1 monotherapy in patients with advanced NSCLC. 
      Further investigation of the combination immunotherapy in specific subsets of 
      patients is warranted to identify and define the patient-specific benefits of 
      this combination. Systematic Review Registration: 
      https://www.crd.york.ac.uk/prospero/, identifier CRD42023435399.
CI  - Copyright (c) 2024 Lin, Xiao, Li, Chen, Zhang, Yu, Zhang, Wei and Li.
FAU - Lin, Li
AU  - Lin L
AD  - Department of Oncology, Wuhan Asia General Hospital, Wuhan, China.
FAU - Xiao, Lu
AU  - Xiao L
AD  - Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Li, Lei
AU  - Li L
AD  - Department of Oncology, Wuhan Asia General Hospital, Wuhan, China.
FAU - Chen, Chen
AU  - Chen C
AD  - Department of Oncology, Wuhan Asia General Hospital, Wuhan, China.
FAU - Zhang, Haorong
AU  - Zhang H
AD  - Department of Oncology, Wuhan Asia General Hospital, Wuhan, China.
FAU - Yu, Changyan
AU  - Yu C
AD  - Department of Oncology, Wuhan Asia General Hospital, Wuhan, China.
FAU - Zhang, Lanfang
AU  - Zhang L
AD  - Department of Oncology, Wuhan Asia General Hospital, Wuhan, China.
FAU - Wei, Anhua
AU  - Wei A
AD  - Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Systematic Review
DEP - 20240205
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10877718
OTO - NOTNLM
OT  - CTLA-4 inhibitor
OT  - NSCLC
OT  - PD-1/PD-L1 inhibitor
OT  - meta-analysis
OT  - non-small cell lung cancer
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/02/21 11:15
MHDA- 2024/02/21 11:16
PMCR- 2024/02/05
CRDT- 2024/02/21 04:01
PHST- 2023/07/27 00:00 [received]
PHST- 2024/01/23 00:00 [accepted]
PHST- 2024/02/21 11:16 [medline]
PHST- 2024/02/21 11:15 [pubmed]
PHST- 2024/02/21 04:01 [entrez]
PHST- 2024/02/05 00:00 [pmc-release]
AID - 1267763 [pii]
AID - 10.3389/fphar.2024.1267763 [doi]
PST - epublish
SO  - Front Pharmacol. 2024 Feb 5;15:1267763. doi: 10.3389/fphar.2024.1267763. 
      eCollection 2024.