PMID- 36897735
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230916
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 102
IP  - 10
DP  - 2023 Mar 10
TI  - Efficacy and safety of PD1/PDL1 inhibitors combined with radiotherapy and 
      anti-angiogenic therapy for solid tumors: A systematic review and meta-analysis.
PG  - e33204
LID - 10.1097/MD.0000000000033204 [doi]
LID - e33204
AB  - BACKGROUND: The triple combination of programmed cell death 1 (PD1)/programmed 
      cell death ligand 1 (PDL1) inhibitors, radiotherapy (RT), and anti-angiogenesis 
      agents has been widely used in the treatment of solid tumors and has shown 
      positive efficacy. We conducted a meta-analysis to evaluate the efficacy and 
      safety of PD1/PDL1 inhibitors combined with anti-angiogenic agents and RT for the 
      treatment of solid cancers. METHODS: A systematic search of PubMed, Embase, 
      Cochrane Library, and Web of Science databases was conducted from inception to 
      October 31, 2022. Studies involving patients with solid cancers who received 
      PD1/PDL1 inhibitors combined with RT and anti-angiogenic agents treatment that 
      reported overall response rate, complete remission rate, disease control rate, 
      and adverse events (AEs) were included. A random-effects or fixed-effects model 
      was used for the pooled rates, and 95% confidence intervals (CIs) were determined 
      for all outcomes. The quality of the included literature was assessed using the 
      methodological index for nonrandomized studies critical appraisal checklist. 
      Egger test was used to assess the publication bias in the included studies. 
      RESULTS: Ten studies (4 nonrandomized controlled trials and 6 single-arm trials), 
      including 365 patients, were identified and included in the meta-analysis. The 
      pooled overall response rate after treatment with PD1/PDL1 inhibitors combined 
      with RT and anti-angiogenic agents was 59% (95% CI: 48-70%), whereas the disease 
      control rate and complete remission rate were 92% (95% CI: 81-103%) and 48% (95% 
      CI: 35-61%), respectively. Moreover, the meta-analysis showed that compared with 
      triple-regimen, monotherapy or dual-combination treatment did not improve overall 
      survival (hazard ratio = 0.499, 95% CI: 0.399-0.734) and progression-free 
      survival (hazard ratio = 0.522, 95% CI: 0.352-0.774). The pooled rate of grade 3 
      to 4 AEs was 26.9% (95% CI: 7.8%-45.9), and the common AEs to triple therapy 
      included leukopenia (25%), thrombocytopenia (23.8%), fatigue (23.2%), 
      gastrointestinal discomfort (22%), increased alanine aminotransferase (22%), and 
      neutropenia (21.4%). CONCLUSION: In the treatment of solid tumors, PD1/PDL1 
      inhibitors combined with RT and anti-angiogenic drugs achieved a positive 
      response and better survival benefits than monotherapy or dual therapy. In 
      addition, combination therapy is tolerable and safe. REGISTRATION: PROSPERO ID: 
      CRD42022371433.
CI  - Copyright (c) 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
FAU - Xian, Feng
AU  - Xian F
AUID- ORCID: 0000-0002-1310-3506
AD  - Department of Oncology, Nanchong Central Hospital, The Second Clinical Institute 
      of North Sichuan Medical College, Nanchong, China.
AD  - School of Medicine, University of Electronic Science and Technology of China, 
      Chengdu, China.
FAU - Wu, Jing
AU  - Wu J
AD  - Department of Operations Management, Nanchong Central Hospital, The Second 
      Clinical Institute of North Sichuan Medical College, Nanchong, China.
FAU - Zhong, Liming
AU  - Zhong L
AD  - Department of Operations Management, Nanchong Central Hospital, The Second 
      Clinical Institute of North Sichuan Medical College, Nanchong, China.
FAU - Xu, Guohui
AU  - Xu G
AD  - School of Medicine, University of Electronic Science and Technology of China, 
      Chengdu, China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Angiogenesis Inhibitors)
SB  - IM
MH  - Humans
MH  - *Neoplasms/drug therapy
MH  - Angiogenesis Inhibitors/therapeutic use
MH  - Immunotherapy
PMC - PMC9997836
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2023/03/11 06:00
MHDA- 2023/03/15 06:00
PMCR- 2023/03/10
CRDT- 2023/03/10 12:04
PHST- 2023/03/10 12:04 [entrez]
PHST- 2023/03/11 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/03/10 00:00 [pmc-release]
AID - 00005792-202303100-00070 [pii]
AID - 10.1097/MD.0000000000033204 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2023 Mar 10;102(10):e33204. doi: 
      10.1097/MD.0000000000033204.