PMID- 35296556
OWN - NLM
STAT- MEDLINE
DCOM- 20220405
LR  - 20220712
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 10
IP  - 3
DP  - 2022 Mar
TI  - Efficacy and safety of neoadjuvant sintilimab, oxaliplatin and capecitabine in 
      patients with locally advanced, resectable gastric or gastroesophageal junction 
      adenocarcinoma: early results of a phase 2 study.
LID - 10.1136/jitc-2021-003635 [doi]
LID - e003635
AB  - Immune checkpoint inhibitors have greatly improved the prognoses of diverse 
      advanced malignancies, including gastric and gastroesophageal junction (G/GEJ) 
      cancer. However, the role of anti-programmed cell death protein-1 treatment in 
      the neoadjuvant setting remains unclear. This phase 2 study aimed to evaluate 
      sintilimab plus CapeOx as a neoadjuvant regimen in patients with advanced 
      resectable G/GEJ adenocarcinoma. Eligible patients with resectable G/GEJ 
      adenocarcinoma stage cT3-4NanyM0 were enrolled. Patients received neoadjuvant 
      treatment with sintilimab (3 mg/kg for cases <60 kg or 200 mg for those >/=60 kg on 
      day 1) plus CapeOx (oxaliplatin at 130 mg/m(2) on D1 and capecitabine at 1000 
      mg/m(2) two times per day on D1-D14) every 21 days, for three cycles before 
      surgical resection, followed by adjuvant treatment with three cycles of CapeOx 
      with the same dosages after surgical resection. The primary endpoint was 
      pathological complete response (pCR) rate. Secondary endpoints included objective 
      response rate, tumor regression grade per Becker criteria, survival and safety. 
      As of July 30, 2020, 36 patients were enrolled. Totally 7 (19.4%) patients had 
      GEJ cancer, and 34 (94.4%) patients were clinical stage III cases. A total of 35 
      (97.2%) patients completed three cycles of neoadjuvant treatment, and 1 patients 
      received two cycles due to adverse events. All patients underwent surgery and the 
      R0 resection rate was 97.2%. In this study, pCR and major pathological response 
      were achieved in 7 (19.4%, 95% CI: 8.8% to 35.7%; 90% CI: 10.7% to 33.1%) and 17 
      (47.2%, 95% CI: 31.6% to 64.3%) patients, respectively. Thirty-one patients 
      received adjuvant treatment. By December 20, 2021, three patients died after 
      disease relapse, and two patients were alive with relapse. Median disease-free 
      survival (DFS) and overall survival (OS) were not reached. The 1-year DFS and OS 
      rates were 90.3% (95% CI: 80.4% to 100.0%) and 94.1% (95% CI: 86.5% to 100.0%), 
      respectively. The most common (>1 patient) grade 3 treatment-related adverse 
      events during neoadjuvant treatment were anemia and neutropenia (n=5 each, 
      13.9%). No serious adverse events (AEs) or grade 4-5 AEs were observed. 
      Sintilimab plus oxaliplatin/capecitabine showed promising efficacy with 
      encouraging pCR rate and good safety profile in the neoadjuvant setting. This 
      combination regimen might present a new option for patients with locally 
      advanced, resectable G/GEJ adenocarcinoma. Trial registration; NCT04065282.
CI  - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Jiang, Haiping
AU  - Jiang H
AD  - Department of Medical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Yu, Xiongfei
AU  - Yu X
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Li, Ning
AU  - Li N
AD  - Department of Medical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Kong, Mei
AU  - Kong M
AD  - Department of Pathology, The First Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou, China.
FAU - Ma, Zhimin
AU  - Ma Z
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Zhou, Donghui
AU  - Zhou D
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Wang, Weibin
AU  - Wang W
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Wang, Haohao
AU  - Wang H
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Wang, Haiyong
AU  - Wang H
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - He, Kuifeng
AU  - He K
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Li, Zhongqi
AU  - Li Z
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Lu, Yimin
AU  - Lu Y
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Zhao, Kui
AU  - Zhao K
AD  - Department of Nuclear Medicine, PET Centre, The First Affiliated Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
FAU - Zhang, Yafei
AU  - Zhang Y
AD  - Department of Nuclear Medicine, PET Centre, The First Affiliated Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
FAU - Xu, Nong
AU  - Xu N
AD  - Department of Medical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Li, Ziran
AU  - Li Z
AD  - Department of Medical Science and Strategy Oncology, Innovent Biologics, Inc, 
      Suzhou, China.
FAU - Liu, Ying
AU  - Liu Y
AD  - Department of Medical Science and Strategy Oncology, Innovent Biologics, Inc, 
      Suzhou, China.
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Medical Science and Strategy Oncology, Innovent Biologics, Inc, 
      Suzhou, China.
FAU - Wang, Yisen
AU  - Wang Y
AD  - Department of Translational Medicine, Innovent Biologics, Inc, Suzhou, China.
FAU - Teng, Lisong
AU  - Teng L
AD  - Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China lsteng@zju.edu.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT04065282
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 04ZR38536J (Oxaliplatin)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - 8FU7FQ8UPK (sintilimab)
SB  - IM
MH  - *Adenocarcinoma/pathology
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Capecitabine/therapeutic use
MH  - Esophagogastric Junction/pathology
MH  - Humans
MH  - *Neoadjuvant Therapy/methods
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Oxaliplatin/therapeutic use
PMC - PMC8928365
OTO - NOTNLM
OT  - antibodies, neoplasm
OT  - clinical trials as topic
OT  - clinical trials, phase II as topic
OT  - gastrointestinal neoplasms
OT  - immunotherapy
COIS- Competing interests: HJ received advisory fees from Innovent Biologics. ZL, YL 
      and Yan Wang are employees of Innovent Biologics.
EDAT- 2022/03/18 06:00
MHDA- 2022/04/06 06:00
PMCR- 2022/03/16
CRDT- 2022/03/17 05:31
PHST- 2022/02/14 00:00 [accepted]
PHST- 2022/03/17 05:31 [entrez]
PHST- 2022/03/18 06:00 [pubmed]
PHST- 2022/04/06 06:00 [medline]
PHST- 2022/03/16 00:00 [pmc-release]
AID - jitc-2021-003635 [pii]
AID - 10.1136/jitc-2021-003635 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2022 Mar;10(3):e003635. doi: 10.1136/jitc-2021-003635.