PMID- 34101874
OWN - NLM
STAT- MEDLINE
DCOM- 20220204
LR  - 20220204
IS  - 1365-2710 (Electronic)
IS  - 0269-4727 (Linking)
VI  - 46
IP  - 6
DP  - 2021 Dec
TI  - The benefits and risks of CTLA4 inhibitor plus PD1/PDL1 inhibitor in stage 
      IIIB/IV non-small cell lung cancer: A systematic analysis and meta-analysis based 
      on randomized controlled trials.
PG  - 1519-1530
LID - 10.1111/jcpt.13465 [doi]
AB  - WHAT IS KNOWN AND OBJECTIVE: Although immune checkpoint inhibitors (ICIs) have 
      shown clinical benefit for patients with non-small cell lung cancer (NSCLC), the 
      efficacy of the combination of ICIs targeting different pathways is still 
      unclear. We performed this meta-analysis to explore the efficacy of cytotoxic 
      T-lymphocyte-associated protein 4 (CTLA-4) inhibitor plus programmed cell death 1 
      receptor (PD-1)/programmed cell death receptor ligand 1 (PD-L1) inhibitor therapy 
      (CP) for NSCLC IIIB/IV patients. METHODS: We systematically searched the main 
      databases for relevant studies. The main outcomes were overall survival (OS) and 
      progression-free survival (PFS). RESULTS AND DISCUSSION: We identified 3526 
      articles, including 5 randomized controlled trials (RCTs) (4377 patients), in our 
      meta-analysis. We conducted two comparisons of CP versus chemotherapy or PD1/PDL1 
      inhibitor (P). Compared with chemotherapy, CP was more effective, with better OS 
      (hazard ratio [HR]: 0.77, 95% CI [confidence interval]: 0.66-0.91; p = 0.001), 
      better PFS (HR: 0.77, 95% CI: 0.70-0.85; p < 0.00001) and comparable objective 
      response rate (ORR) (risk ratio [RR]: 1.27, 95% CI: 0.98-1.65; p = 0.07); in 
      terms of toxicity, CP was comparable to chemotherapy across all-grade adverse 
      events (AEs) (RR: 0.87, 95% CI: 0.73-1.03; p = 0.11) and grade 3-5 AEs (RR: 0.85, 
      95% CI: 0.63-1.14; p = 0.27). Compared with P, CP had no superiority in efficacy 
      in terms of the OS (HR: 1.04, 95%CI: 0.86-1.24; p=0.70), PFS (HR: 0.95, 95%CI: 
      0.75-1.22; p = 0.70) and the ORR (RR: 1.07, 95% CI: 0.95-1.21; p = 0.27) but CP 
      was more effective than P when PD-L1 expression was <1% (RR: 0.77,95%CI: 
      0.60-0.98; p = 0.04); in terms of toxicity, CP was associated with increased 
      all-grade AEs (RR:1.07, 95% CI: 0.97-1.19; p = 0.18) and grade 3-5 AEs (RR:1.58, 
      95% CI: 1.21-2.07; p = 0.0008). WHAT IS NEW AND CONCLUSION: CP is a beneficial 
      therapeutic schedule with longer PFS and OS than chemotherapy and has an 
      acceptable, manageable grade 3-4 AE rate in IIIB/IV NSCLC. However, compared with 
      P, CP results in better OS only in patients with PD-L1 expression <1%.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Liu, Qiangyun
AU  - Liu Q
AD  - Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, China.
AD  - Jiangxi medical college, Nanchang University, Nanchang, China.
FAU - Fang, Zige
AU  - Fang Z
AUID- ORCID: 0000-0002-1925-3935
AD  - Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, China.
AD  - Jiangxi medical college, Nanchang University, Nanchang, China.
FAU - Liu, Miaowen
AU  - Liu M
AD  - Jiangxi medical college, Nanchang University, Nanchang, China.
AD  - Department of Oncology, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, China.
FAU - Xu, Ruoxin
AU  - Xu R
AD  - Jiangxi medical college, Nanchang University, Nanchang, China.
AD  - Department of Oncology, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, China.
FAU - Yi, Fengming
AU  - Yi F
AD  - Department of Oncology, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, China.
FAU - Wei, Yiping
AU  - Wei Y
AD  - Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, China.
FAU - Zeng, Linxiang
AU  - Zeng L
AD  - Department of Emergency and Critical Care Medicine, The Second Affiliated 
      Hospital of Nanchang University, Nanchang, China.
FAU - Zhang, Wenxiong
AU  - Zhang W
AUID- ORCID: 0000-0003-2962-0847
AD  - Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, China.
LA  - eng
GR  - 81560345/National Natural Science Foundation of China/
GR  - 20181BAB215027/Natural Science Foundation of Jiangxi Province/
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20210608
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Antineoplastic Agents, Immunological/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/*therapeutic use
MH  - B7-H1 Antigen/*antagonists & inhibitors
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Humans
MH  - Immune Checkpoint Inhibitors/administration & dosage/adverse effects/*therapeutic 
      use
MH  - Lung Neoplasms/*drug therapy
MH  - Neoplasm Staging
MH  - Randomized Controlled Trials as Topic
OTO - NOTNLM
OT  - CTLA4 inhibitor
OT  - PD1/PDL1 inhibitor
OT  - meta-analysis
OT  - non-small cell lung cancer
OT  - systematic analysis
EDAT- 2021/06/09 06:00
MHDA- 2022/02/05 06:00
CRDT- 2021/06/08 17:38
PHST- 2021/05/21 00:00 [revised]
PHST- 2021/04/25 00:00 [received]
PHST- 2021/05/24 00:00 [accepted]
PHST- 2021/06/09 06:00 [pubmed]
PHST- 2022/02/05 06:00 [medline]
PHST- 2021/06/08 17:38 [entrez]
AID - 10.1111/jcpt.13465 [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2021 Dec;46(6):1519-1530. doi: 10.1111/jcpt.13465. Epub 2021 
      Jun 8.