PMID- 35747163
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221115
IS  - 1758-8340 (Print)
IS  - 1758-8359 (Electronic)
IS  - 1758-8340 (Linking)
VI  - 14
DP  - 2022
TI  - Network meta-analysis of immune-oncology monotherapy as first-line treatment for 
      advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50.
PG  - 17588359221105024
LID - 10.1177/17588359221105024 [doi]
LID - 17588359221105024
AB  - BACKGROUND: For patients with advanced non-small-cell lung cancer (NSCLC) and 
      high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective 
      first-line immune-oncology monotherapies with significant survival benefits are 
      approved, cemiplimab being the most recent. In a phase III trial, cemiplimab 
      demonstrated significantly improved overall survival (OS) and progression-free 
      survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 
      ⩾50%. A systematic literature review and network meta-analysis (NMA) was 
      conducted to identify/compare the efficacy/safety of cemiplimab versus 
      pembrolizumab or other immune-oncology monotherapies from randomized-controlled 
      trials (RCTs) published in November 2010-2020. METHODS: Relevant RCTs were 
      identified by searching databases and conference proceedings as per ISPOR, NICE, 
      and Preferred Reporting Items for Systematic Reviews and Meta-Analyses 
      guidelines. NMA with time-varying hazard ratios (HRs) was performed for OS and 
      PFS. Analyses were conducted for objective response rate (ORR) and 
      safety/tolerability. Fixed-effect models were used due to limited evidence. 
      Various sensitivity analyses were conducted to validate the base case analyses. 
      RESULTS: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, 
      and KEYNOTE-042 trials were eligible. IMpower110 was excluded because an 
      incompatible PD-L1 assay (SP142) was used for patient selection. For first-line 
      advanced NSCLC with PD-L1 ⩾50%, cemiplimab was associated with statistically 
      significant improvements in PFS [HR (95% credible interval [CrI]): 0.65 
      (0.50-0.86), 1-12 months] and ORR [odds ratio (OR) (95% CrI): 1.64 (1.04-2.62)], 
      and comparable OS [HR (95% CrI): 0.77 (0.54-1.10), 1-12 months] versus 
      pembrolizumab. There was no evidence of differences between cemiplimab and 
      pembrolizumab for Grade 3-5 adverse events (AEs) [OR (95% CrI): 1.47 
      (0.83-2.60)], immune-mediated AEs [1.75 (0.33-7.49)], and all-cause 
      discontinuation due to AEs [1.21 (0.58-2.61)]. CONCLUSIONS: Considering the 
      limitations of indirect treatment comparisons, in patients with advanced NSCLC 
      and PD-L1 ⩾50%, cemiplimab monotherapy demonstrated significant improvements in 
      PFS and ORR, comparable OS, and no evidence of differences in safety/tolerability 
      versus pembrolizumab.
CI  - (c) The Author(s), 2022.
FAU - Freemantle, Nick
AU  - Freemantle N
AUID- ORCID: 0000-0001-5807-5740
AD  - Comprehensive Clinical Trials Unit, University College London, Institute of 
      Clinical Trials and Methodology, 90 High Holborn 2nd Floor, London WC1V 6LJ, UK.
FAU - Xu, Yingxin
AU  - Xu Y
AD  - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
FAU - Wilson, Florence R
AU  - Wilson FR
AD  - Precision HEOR, Vancouver, BC, Canada.
FAU - Guyot, Patricia
AU  - Guyot P
AD  - Sanofi, Chilly-Mazarin, France.
FAU - Chen, Chieh-I
AU  - Chen CI
AD  - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
FAU - Keeping, Sam
AU  - Keeping S
AD  - Precision HEOR, Vancouver, BC, Canada.
FAU - Konidaris, Gerasimos
AU  - Konidaris G
AD  - Sanofi, Reading, UK.
FAU - Chan, Keith
AU  - Chan K
AD  - Precision HEOR, Vancouver, BC, Canada.
FAU - Kuznik, Andreas
AU  - Kuznik A
AD  - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
FAU - Atsou, Kokuvi
AU  - Atsou K
AD  - Sanofi, Chilly-Mazarin, France.
FAU - Glowienka, Emily
AU  - Glowienka E
AD  - Precision HEOR, Boston, MA, USA.
FAU - Pouliot, Jean-Francois
AU  - Pouliot JF
AD  - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
FAU - Gullo, Giuseppe
AU  - Gullo G
AD  - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
FAU - Rietschel, Petra
AU  - Rietschel P
AD  - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
LA  - eng
PT  - Journal Article
DEP - 20220616
PL  - England
TA  - Ther Adv Med Oncol
JT  - Therapeutic advances in medical oncology
JID - 101510808
EIN - Ther Adv Med Oncol. 2022 Sep 13;14:17588359221127078. PMID: 36119642
PMC - PMC9210099
OTO - NOTNLM
OT  - IO monotherapy
OT  - PD-L1 expression
OT  - cemiplimab
OT  - cemiplimab monotherapy
OT  - network meta-analysis
OT  - non-small-cell lung cancer
OT  - systematic literature review
COIS- Conflict of interest statement: Nick Freemantle declares consulting services for 
      ALK, Allergan, Aimmune, AstraZeneca, Gilead, Grifols, Ipsen, MSD, Novartis, Novo 
      Nordisk, Sanofi Aventis, and Vertex; and speaking services for Abbott Singapore 
      and Sanofi Aventis. Yingxin Xu, Chieh-I Chen, Andreas Kuznik, Jean-Francois 
      Pouliot, Giuseppe Gullo, and Petra Rietschel are employees and stockholders of 
      Regeneron Pharmaceuticals, Inc. Florence R. Wilson, Sam Keeping, Keith Chan, and 
      Emily Glowienka are employees of Precision HEOR and received funding to produce 
      this work. Patricia Guyot, Gerasimos Konidaris, and Kokuvi Atsou are employees of 
      Sanofi and may own shares or stock options in the company.
EDAT- 2022/06/25 06:00
MHDA- 2022/06/25 06:01
PMCR- 2022/06/16
CRDT- 2022/06/24 02:07
PHST- 2021/11/12 00:00 [received]
PHST- 2022/05/16 00:00 [accepted]
PHST- 2022/06/24 02:07 [entrez]
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/06/25 06:01 [medline]
PHST- 2022/06/16 00:00 [pmc-release]
AID - 10.1177_17588359221105024 [pii]
AID - 10.1177/17588359221105024 [doi]
PST - epublish
SO  - Ther Adv Med Oncol. 2022 Jun 16;14:17588359221105024. doi: 
      10.1177/17588359221105024. eCollection 2022.