PMID- 33314747
OWN - NLM
STAT- MEDLINE
DCOM- 20210820
LR  - 20210820
IS  - 2523-3548 (Electronic)
IS  - 2523-3548 (Linking)
VI  - 40
IP  - 12
DP  - 2020 Dec
TI  - Phase II clinical trial using camrelizumab combined with apatinib and 
      chemotherapy as the first-line treatment of advanced esophageal squamous cell 
      carcinoma.
PG  - 711-720
LID - 10.1002/cac2.12119 [doi]
AB  - BACKGROUND: Effective therapeutic options are limited for patients with advanced 
      esophageal squamous cell carcinoma (ESCC). The incorporation of an immune 
      checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly 
      adopted chemotherapy may produce synergistic effects. Therefore, we aimed to 
      investigate the efficacy and safety of camrelizumab plus apatinib combined with 
      chemotherapy as the first-line treatment of advanced ESCC. METHODS: In this 
      single-arm prospective phase II trial, patients with unresectable locally 
      advanced or recurrent/metastatic ESCC received camrelizumab 200 mg, liposomal 
      paclitaxel 150 mg/m(2) , and nedaplatin 50 mg/m(2) on day 1, and apatinib 250 mg 
      on days 1-14. The treatments were repeated every 14 days for up to 9 cycles, 
      followed by maintenance therapy with camrelizumab and apatinib. The primary 
      endpoint was objective response rate (ORR) according to the Response Evaluation 
      Criteria in Solid Tumors (version 1.1). Secondary endpoints included disease 
      control rate (DCR), progression-free survival (PFS), overall survival (OS), and 
      safety. RESULTS: We enrolled 30 patients between August 7, 2018 and February 23, 
      2019. The median follow-up was 24.98 months (95% confidence interval [CI]: 
      23.05-26.16 months). The centrally assessed ORR was 80.0% (95% CI: 61.4%-92.3%), 
      with a median duration of response of 9.77 months (range: 1.54 to 24.82+ months). 
      The DCR reached 96.7% (95% CI: 82.8%-99.9%). The median PFS was 6.85 months (95% 
      CI: 4.46-14.20 months), and the median OS was 19.43 months (95% CI: 9.93 months - 
      not reached). The most common grade 3-4 treatment-related adverse events (AEs) 
      were leukopenia (83.3%), neutropenia (60.0%), and increased aspartate 
      aminotransferase level (26.7%). Treatment-related serious AEs included febrile 
      neutropenia, leukopenia, and anorexia in one patient (3.3%), and single cases of 
      increased blood bilirubin level (3.3%) and toxic epidermal necrolysis (3.3%). No 
      treatment-related deaths occurred. CONCLUSIONS: Camrelizumab plus apatinib 
      combined with liposomal paclitaxel and nedaplatin as first-line treatment 
      demonstrated feasible anti-tumor activity and manageable safety in patients with 
      advanced ESCC. Randomized trials to evaluate this new combination strategy are 
      warranted. TRIAL REGISTRATION: This trial was registered on July 27, 2018, at 
      ClinicalTrials.gov (identifier: NCT03603756).
CI  - (c) 2020 The Authors. Cancer Communications published by John Wiley & Sons 
      Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.
FAU - Zhang, Bo
AU  - Zhang B
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, 100021, P. R. China.
FAU - Qi, Ling
AU  - Qi L
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, 100021, P. R. China.
FAU - Wang, Xi
AU  - Wang X
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, 100021, P. R. China.
FAU - Xu, Jianping
AU  - Xu J
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, 100021, P. R. China.
FAU - Liu, Yun
AU  - Liu Y
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, 100021, P. R. China.
FAU - Mu, Lan
AU  - Mu L
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, 100021, P. R. China.
FAU - Wang, Xingyuan
AU  - Wang X
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, 100021, P. R. China.
FAU - Bai, Lidan
AU  - Bai L
AD  - Jiangsu Hengrui Medicine Co. Ltd., Lianyungang, Jiangsu, 222047, P. R. China.
FAU - Huang, Jing
AU  - Huang J
AUID- ORCID: 0000-0002-2167-8385
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, 100021, P. R. China.
LA  - eng
SI  - ClinicalTrials.gov/NCT03603756
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201212
PL  - United States
TA  - Cancer Commun (Lond)
JT  - Cancer communications (London, England)
JID - 101723675
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Pyridines)
RN  - 5S371K6132 (apatinib)
RN  - 73096E137E (camrelizumab)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - *Esophageal Neoplasms/drug therapy
MH  - *Esophageal Squamous Cell Carcinoma/drug therapy
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local
MH  - Prospective Studies
MH  - Pyridines/*therapeutic use
PMC - PMC7743020
OTO - NOTNLM
OT  - anti-angiogenesis
OT  - apatinib
OT  - camrelizumab
OT  - chemotherapy
OT  - esophageal squamous cell carcinoma
OT  - first-line
OT  - immunotherapy
OT  - liposomal paclitaxel
OT  - nedaplatin
OT  - objective response rate
COIS- LB is an employee of Jiangsu Hengrui Medicine Co. Ltd; other authors declare no 
      potential conflict of interest.
EDAT- 2020/12/15 06:00
MHDA- 2021/08/21 06:00
PMCR- 2020/12/12
CRDT- 2020/12/14 11:18
PHST- 2020/08/28 00:00 [received]
PHST- 2020/10/07 00:00 [revised]
PHST- 2020/11/26 00:00 [accepted]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2021/08/21 06:00 [medline]
PHST- 2020/12/14 11:18 [entrez]
PHST- 2020/12/12 00:00 [pmc-release]
AID - CAC212119 [pii]
AID - 10.1002/cac2.12119 [doi]
PST - ppublish
SO  - Cancer Commun (Lond). 2020 Dec;40(12):711-720. doi: 10.1002/cac2.12119. Epub 2020 
      Dec 12.