PMID- 35625837
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230308
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 10
IP  - 5
DP  - 2022 May 10
TI  - Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus 
      Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis.
LID - 10.3390/biomedicines10051101 [doi]
LID - 1101
AB  - Background: Recently, the combination of durvalumab and tremelimumab, two immune 
      checkpoint inhibitors, for the treatment of different types of cancers has been 
      considered; however, its overall effects, including its safety, are still unclear 
      and need to be further investigated. Objectives: The aim of the present 
      systematic review and meta-analysis was to investigate the safety and 
      tolerability of this combination of drugs. Methods: A systematic review of the 
      literature, based on the Preferred Reporting Items for Systematic Reviews and 
      Meta-analyses (PRISMA) statement, was conducted by employing online electronic 
      databases and the American Society of Clinical Oncology (ASCO) Meeting Library. 
      The selection of eligible publications was made following a staged screening and 
      selection process. The software RevMan 5.4 was used to run the quantitative 
      analysis and forest plots, while the Cochrane tool was employed for risk of bias 
      assessment. Results: From the retrieved 157 results, 9 randomized controlled 
      trials involving 3060 patients were included. By comparing the combination of 
      durvalumab and tremelimumab vs. durvalumab monotherapy, it was observed that: 
      adverse events (AEs) >/= Grade 3 incidence was 32.6% (536/1646) vs. 23.8% 
      (336/1414) (Z = 2.80; p = 0.005; risk ratio (RR) = 1.44), reduced appetite 
      incidence was 10.8% (154/1427) vs. 8.3% (108/1305) (Z = 2.26; p = 0.02; RR = 
      1.31), diarrhea was reported in 15.6% (229/1473) vs. 8.1% (110/1352) (Z = 5.90; p 
      < 0.00001; RR = 1.91), rash incidence was equal to 11.1% (160/1441) vs. 6.5% 
      (86/1320) (Z = 4.35; p <0.0001; RR = 1.75), pruritis was 13.6% (201/1473) vs. 
      7.7% (104/1352) (Z = 5.35; p < 0.00001; RR = 1.83), fever was 10.5% (42/399) vs. 
      6.6% (22/330) (Z = 2.27; p = 0.02; RR = 1.77), discontinuation rate was 18% 
      (91/504) vs. 3% (36/434) (Z = 4.78; p < 0.00001; RR = 2.41), and death rate was 
      2.6% (13/504) vs. 0.7% (3/434) (Z = 1.90; p = 0.06; RR = 2.77). Conclusions: It 
      was observed that the combined (durvalumab and tremelimumab) vs. monotherapy 
      (durvalumab) is associated with a higher risk of treatment discontinuation, 
      mortality, fever, diarrhea, rash, pruritis, and reduced appetite. This 
      information is relevant and should be disclosed, especially to patients that are 
      currently enrolled in clinical trials considering this combined therapy.
FAU - Fahmy, Omar
AU  - Fahmy O
AD  - Department of Urology, Universiti Putra Malaysia, Selangor 43400, Malaysia.
FAU - Ahmed, Osama A A
AU  - Ahmed OAA
AUID- ORCID: 0000-0002-3204-381X
AD  - Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, 
      Jeddah 21589, Saudi Arabia.
AD  - Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz 
      University, Jeddah 21589, Saudi Arabia.
AD  - Center of Excellence for Drug Research and Pharmaceutical Industries, King 
      Abdulaziz University, Jeddah 21589, Saudi Arabia.
FAU - Khairul-Asri, Mohd Ghani
AU  - Khairul-Asri MG
AD  - Department of Urology, Universiti Putra Malaysia, Selangor 43400, Malaysia.
FAU - Alhakamy, Nabil A
AU  - Alhakamy NA
AUID- ORCID: 0000-0002-3826-1519
AD  - Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, 
      Jeddah 21589, Saudi Arabia.
AD  - Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz 
      University, Jeddah 21589, Saudi Arabia.
AD  - Center of Excellence for Drug Research and Pharmaceutical Industries, King 
      Abdulaziz University, Jeddah 21589, Saudi Arabia.
AD  - Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz 
      University, Jeddah 21589, Saudi Arabia.
FAU - Alharbi, Waleed S
AU  - Alharbi WS
AUID- ORCID: 0000-0001-7727-6126
AD  - Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, 
      Jeddah 21589, Saudi Arabia.
AD  - Center of Excellence for Drug Research and Pharmaceutical Industries, King 
      Abdulaziz University, Jeddah 21589, Saudi Arabia.
FAU - Fahmy, Usama A
AU  - Fahmy UA
AUID- ORCID: 0000-0002-6094-5570
AD  - Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, 
      Jeddah 21589, Saudi Arabia.
AD  - Center of Excellence for Drug Research and Pharmaceutical Industries, King 
      Abdulaziz University, Jeddah 21589, Saudi Arabia.
FAU - El-Moselhy, Mohamed A
AU  - El-Moselhy MA
AD  - Clinical Pharmacy and Pharmacology Department, Ibn Sina National College for 
      Medical Studies, Jeddah 21589, Saudi Arabia.
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 
      Minia 61519, Egypt.
FAU - Fresta, Claudia G
AU  - Fresta CG
AD  - Department of Drug and Health Sciences, University of Catania, 95125 Catania, 
      Italy.
FAU - Caruso, Giuseppe
AU  - Caruso G
AUID- ORCID: 0000-0003-1571-5327
AD  - Department of Drug and Health Sciences, University of Catania, 95125 Catania, 
      Italy.
AD  - Unit of Neuropharmacology and Translational Neurosciences, Oasi Research 
      Institute-IRCCS, 94018 Troina, Italy.
FAU - Caraci, Filippo
AU  - Caraci F
AD  - Department of Drug and Health Sciences, University of Catania, 95125 Catania, 
      Italy.
AD  - Unit of Neuropharmacology and Translational Neurosciences, Oasi Research 
      Institute-IRCCS, 94018 Troina, Italy.
LA  - eng
GR  - FP-028-43/Deanship of Scientific Research (DSR) at King Abdulaziz University/
PT  - Journal Article
PT  - Review
DEP - 20220510
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC9138649
OTO - NOTNLM
OT  - adverse effects
OT  - checkpoint inhibitors
OT  - combined therapy
OT  - durvalumab
OT  - monotherapy
OT  - tremelimumab
COIS- The authors declare no conflict of interest.
EDAT- 2022/05/29 06:00
MHDA- 2022/05/29 06:01
PMCR- 2022/05/10
CRDT- 2022/05/28 01:08
PHST- 2022/03/20 00:00 [received]
PHST- 2022/04/30 00:00 [revised]
PHST- 2022/05/02 00:00 [accepted]
PHST- 2022/05/28 01:08 [entrez]
PHST- 2022/05/29 06:00 [pubmed]
PHST- 2022/05/29 06:01 [medline]
PHST- 2022/05/10 00:00 [pmc-release]
AID - biomedicines10051101 [pii]
AID - biomedicines-10-01101 [pii]
AID - 10.3390/biomedicines10051101 [doi]
PST - epublish
SO  - Biomedicines. 2022 May 10;10(5):1101. doi: 10.3390/biomedicines10051101.