PMID- 33338862
OWN - NLM
STAT- MEDLINE
DCOM- 20210526
LR  - 20210526
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 91
DP  - 2021 Feb
TI  - Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and 
      lenvatinib monotherapies in cancers: A systematic review.
PG  - 107281
LID - S1567-5769(20)33748-6 [pii]
LID - 10.1016/j.intimp.2020.107281 [doi]
AB  - OBJECTIVE: Both pembrolizumab and lenvatinib demonstrate antitumor activity and 
      safety in cancers. However, whether their combination is safer and more effective 
      than monotherapies remains unknown. A systematic review was performed to assess 
      the safety and efficacy of pembrolizumab plus lenvatinib versus their respective 
      monotherapies in solid cancers. METHODS: PubMed, Embase, and Cochrane Library 
      were searched. Forty-two clinical trials with 8155 patients were included. 
      RESULTS: The total >/=grade 3 adverse events (AEs) and objective response rates 
      (ORRs) among pembrolizumab plus lenvatinib and pembrolizumab or lenvatinib 
      monotherapies in solid cancers were 68.0% vs 17.7% vs 68.5% and 40.6% vs 20.8% vs 
      43.3%, respectively. The most common AEs of pembrolizumab plus lenvatinib were 
      hypertension (20-61.1%), fatigue (12-59.1%), diarrhea (9-51.9%), hypothyroidism 
      (25-47%), and proteinuria (8-17%). Good ORRs for combination therapy were 
      observed in renal cell carcinoma (70%), gastric cancer (69%), melanoma (48%), 
      head and neck squamous cell carcinoma (46%), and endometrial cancer (38-53%), 
      while these rates were reported as 27%, 11.6-22%, 26-37%, 14.6-23%, and 11-14.3% 
      for monotherapies, respectively. Longer median progression-free survival (mPFS) 
      and median overall survival (mOS) were observed for hepatocellular carcinoma 
      (mPFS 9.3 months, mOS 22.0 months), renal cell carcinoma (mPFS 19.8 months), 
      gastric cancer (mPFS 7.1 months, mOS not reached), and endometrial cancer (mPFS 
      7.4 months, mOS 16.7 months). CONCLUSIONS: Compared with their monotherapies, 
      pembrolizumab plus lenvatinib showed more promising antitumor activity and 
      resulted in higher ORRs and significant survival benefits in the above cancers. 
      Toxicities were manageable, with no unexpected safety issues.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Mo, Dun-Chang
AU  - Mo DC
AD  - Radiotherapy Department, The Third Affiliated Hospital of Guangxi Medical 
      University, Nanning 530031, Guangxi, China.
FAU - Luo, Peng-Hui
AU  - Luo PH
AD  - Radiotherapy Department, The Third Affiliated Hospital of Guangxi Medical 
      University, Nanning 530031, Guangxi, China.
FAU - Huang, Shang-Xiao
AU  - Huang SX
AD  - Radiotherapy Department, The Third Affiliated Hospital of Guangxi Medical 
      University, Nanning 530031, Guangxi, China.
FAU - Wang, Han-Lei
AU  - Wang HL
AD  - Radiotherapy Department, The Third Affiliated Hospital of Guangxi Medical 
      University, Nanning 530031, Guangxi, China.
FAU - Huang, Jian-Feng
AU  - Huang JF
AD  - Radiotherapy Department, The Third Affiliated Hospital of Guangxi Medical 
      University, Nanning 530031, Guangxi, China. Electronic address: nnhjf520@163.com.
LA  - eng
PT  - Journal Article
PT  - Systematic Review
DEP - 20201216
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Quinolines)
RN  - DPT0O3T46P (pembrolizumab)
RN  - EE083865G2 (lenvatinib)
SB  - IM
MH  - Angiogenesis Inhibitors/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
MH  - Antineoplastic Agents, Immunological/adverse effects/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Clinical Trials as Topic
MH  - Humans
MH  - Neoplasms/*drug therapy/mortality/pathology
MH  - Phenylurea Compounds/adverse effects/*therapeutic use
MH  - Progression-Free Survival
MH  - Quinolines/adverse effects/*therapeutic use
MH  - Time Factors
OTO - NOTNLM
OT  - Lenvatinib
OT  - Monotherapy
OT  - Pembrolizumab
OT  - Safety and efficacy
OT  - Systematic review
EDAT- 2020/12/19 06:00
MHDA- 2021/05/27 06:00
CRDT- 2020/12/18 20:14
PHST- 2020/09/26 00:00 [received]
PHST- 2020/12/03 00:00 [revised]
PHST- 2020/12/03 00:00 [accepted]
PHST- 2020/12/19 06:00 [pubmed]
PHST- 2021/05/27 06:00 [medline]
PHST- 2020/12/18 20:14 [entrez]
AID - S1567-5769(20)33748-6 [pii]
AID - 10.1016/j.intimp.2020.107281 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2021 Feb;91:107281. doi: 10.1016/j.intimp.2020.107281. Epub 
      2020 Dec 16.