PMID- 34692475
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220427
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Anlotinib Combined With Anti-PD-1 Antibodies Therapy in Patients With Advanced 
      Refractory Solid Tumors: A Single-Center, Observational, Prospective Study.
PG  - 683502
LID - 10.3389/fonc.2021.683502 [doi]
LID - 683502
AB  - INTRODUCTION: Anlotinib (AL3818) is a novel multi-target tyrosine kinase 
      inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR) and 
      suppressing tumor growth. Modulation of tumor suppressive immune microenvironment 
      via the inhibition of vascular endothelial growth factor may augment the activity 
      of immune checkpoint inhibitors. Here we described the results of safety, and 
      clinical efficacy of anlotinib combined with immunotherapy in patients with 
      advanced solid tumors, the serum cytokine levels, and peripheral blood T 
      lymphocyte populations were detected simultaneously. METHODS: Twenty six cases 
      with advanced late-stage cancers including lung, gallbladder, endometrial, 
      gastric, pancreatic, penile cancers and melanoma were treated since January 2019. 
      Patients received a combination of anlotinib (12mg) once daily on day 1 to day 14 
      (21 days as a course) plus anti-PD-1 antibodies every 3 weeks until progression 
      or intolerable toxicity. Imaging was performed every 6 weeks for the first year 
      of therapy. Blood samples were collected from patients prospectively. Serum 
      interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor necrosis factor-alpha (TNF-alpha), 
      interferon-gamma (IFN-gamma) and circulating immune cell subsets were measured at 
      baseline and after two cycles of treatment via flow cytometry. RESULTS: There 
      were ten tumor types enrolled with lung, gallbladder, cholangiocarcinoma and soft 
      tissue sarcoma being the most common. Most patients had received front line 
      treatments for metastatic disease (80.8%). The objective response rate (ORR) was 
      23.1%, including one complete response (CR) (3.8%) and five partial responses 
      (PR) (19.2%) and a disease control rate (DCR=CR+PR+SD) of 80.8% (21 of 26). The 
      median PFS was 8.37 months (95% CI: 6.5-10.0 months). Three patients (11.5%) had 
      grade 3 treatment-related adverse events. There were no grade 4 or 5 
      treatment-related adverse events. Grades 3 toxicities included hand-foot syndrome 
      (n=2) and hypertension (n=1). Higher serum IL-2, IL-4, IL-10, TNF-alpha, IFN-gamma levels 
      and lower ratios of CD4/CD8 T cells were found in the responders compared with 
      non-responders. CONCLUSIONS: The preliminary data showed that the combination of 
      anlotinib and anti-PD-1 antibodies demonstrated promising durable antitumor 
      efficacy with acceptable toxicity in patients with various advance tumors, and 
      promoted favorable changes in serum IL-2, IL-4, IL-10, TNF-alpha, IFN-gamma levels and 
      circulating immune cell subsets in clinical responders. It is worth to further 
      validate the efficacy in a randomized prospective trial.
CI  - Copyright (c) 2021 Yuan, Zhu, Mao, Wang, Qian, Wu, Guo and Xu.
FAU - Yuan, Min
AU  - Yuan M
AD  - Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Zhu, Zhongzheng
AU  - Zhu Z
AD  - Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Mao, Wei
AU  - Mao W
AD  - Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Qian, Hong
AU  - Qian H
AD  - Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Wu, Jianguo
AU  - Wu J
AD  - Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Guo, Xianling
AU  - Guo X
AD  - Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Xu, Qing
AU  - Xu Q
AD  - Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20211007
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
EIN - Front Oncol. 2022 Jan 04;11:796625. PMID: 35059318
PMC - PMC8529018
OTO - NOTNLM
OT  - angiogenesis
OT  - anlotinib
OT  - anti-PD-1 antibody
OT  - immunotherapy
OT  - serum cytokine
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/10/26 06:00
MHDA- 2021/10/26 06:01
PMCR- 2021/01/01
CRDT- 2021/10/25 06:38
PHST- 2021/03/26 00:00 [received]
PHST- 2021/09/17 00:00 [accepted]
PHST- 2021/10/25 06:38 [entrez]
PHST- 2021/10/26 06:00 [pubmed]
PHST- 2021/10/26 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.683502 [doi]
PST - epublish
SO  - Front Oncol. 2021 Oct 7;11:683502. doi: 10.3389/fonc.2021.683502. eCollection 
      2021.