PMID- 37582945
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231119
IS  - 2730-664X (Electronic)
IS  - 2730-664X (Linking)
VI  - 3
IP  - 1
DP  - 2023 Aug 15
TI  - Phase I/II clinical trial of nivolumab in combination with oligo-fractionated 
      irradiation for unresectable advanced or recurrent gastric cancer.
PG  - 111
LID - 10.1038/s43856-023-00343-4 [doi]
LID - 111
AB  - BACKGROUND: Although immune checkpoint inhibitors (ICI) targeting for PD-1 axis 
      is a promising approach for advanced gastric cancer (GC) patients, the response 
      rate is still limited. Induction of synergistic effect of irradiation with ICI 
      targeting for the PD-1 axis can be an attractive strategy. The aim of this study 
      was to assess the effect of the combination of irradiation with anti-PD-1 therapy 
      for advanced GC. METHODS: We conducted a single-arm, phase I/II trial in GC 
      patients treated with a combination of nivolumab and oligo-fractionated 
      irradiation (22.5 Gy/5 fractions/5 days) (NCT03453164). Eligible patients 
      (n = 40) had unresectable advanced or recurrent GC which progressed after primary 
      and secondary chemotherapy with more than one lesion. The primary endpoint is the 
      disease control rate (DCR) of non-irradiated target lesions and the secondary 
      endpoints are the median survival time (MST), safety, and DCR of irradiated 
      lesions. RESULTS: We observe that the DCR for the non-irradiated target as the 
      abscopal effect is 22.5% (90% confidence interval (CI), 12.3-36.0), and the DCR 
      for the irradiated lesion is 40.0% (90% CI, 26.9-54.2). The median survival time 
      is 230 days (95% CI, 157-330), and grade 3 and higher adverse events (AEs) are 
      observed in 16 patients (39 %) with no obvious additional AEs when adding 
      irradiation. CONCLUSIONS: The present study suggests that the combination of 
      nivolumab with oligo-fractionated irradiation has the potential to induce a 
      promising anti-tumor effect for advanced GC.
CI  - (c) 2023. Springer Nature Limited.
FAU - Mimura, Kosaku
AU  - Mimura K
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
AD  - Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical 
      University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Ogata, Takashi
AU  - Ogata T
AD  - Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao 
      Asahi, Yokohama, 241-8515, Japan.
FAU - Yoshimoto, Yuya
AU  - Yoshimoto Y
AD  - Department of Radiation Oncology, Fukushima Medical University School of 
      Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Yoshida, Daisaku
AU  - Yoshida D
AD  - Department of Radiation Oncology, Kanagawa Cancer Center, 2-3-2 Nakao Asahi, 
      Yokohama, 241-8515, Japan.
FAU - Nakajima, Shotaro
AU  - Nakajima S
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Sato, Hisashi
AU  - Sato H
AD  - Department of Radiation Oncology, Fukushima Medical University School of 
      Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Machida, Nozomu
AU  - Machida N
AD  - Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao Asahi, 
      Yokohama, 241-8515, Japan.
FAU - Yamada, Takanobu
AU  - Yamada T
AD  - Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao 
      Asahi, Yokohama, 241-8515, Japan.
FAU - Watanabe, Yohei
AU  - Watanabe Y
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Tamaki, Tomoaki
AU  - Tamaki T
AD  - Department of Radiation Oncology, Fukushima Medical University School of 
      Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Fujikawa, Hirohito
AU  - Fujikawa H
AD  - Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao 
      Asahi, Yokohama, 241-8515, Japan.
FAU - Inokuchi, Yasuhiro
AU  - Inokuchi Y
AD  - Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao Asahi, 
      Yokohama, 241-8515, Japan.
FAU - Hayase, Suguru
AU  - Hayase S
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Hanayama, Hiroyuki
AU  - Hanayama H
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Saze, Zenichiro
AU  - Saze Z
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Katoh, Hiroyuki
AU  - Katoh H
AD  - Department of Radiation Oncology, Kanagawa Cancer Center, 2-3-2 Nakao Asahi, 
      Yokohama, 241-8515, Japan.
FAU - Takahashi, Fumiaki
AU  - Takahashi F
AUID- ORCID: 0000-0001-9201-1089
AD  - Department of Information Science, Iwate Medical University, 1-1-1 Idaidori, 
      Yahaba, Shiwa, Iwate, 028-3694, Japan.
FAU - Oshima, Takashi
AU  - Oshima T
AD  - Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao 
      Asahi, Yokohama, 241-8515, Japan.
FAU - Suzuki, Yoshiyuki
AU  - Suzuki Y
AD  - Department of Radiation Oncology, Fukushima Medical University School of 
      Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
FAU - Kono, Koji
AU  - Kono K
AUID- ORCID: 0000-0003-0106-2767
AD  - Department of Gastrointestinal Tract Surgery, Fukushima Medical University School 
      of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan. kojikono@fmu.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20230815
PL  - England
TA  - Commun Med (Lond)
JT  - Communications medicine
JID - 9918250414506676
PMC - PMC10427681
OAB - Immunotherapy is a type of treatment that triggers the immune system to kill 
      cancers. Combining immunotherapy with radiotherapy may enhance its effects. We 
      evaluated this in a clinical trial in which we treated patients with advanced or 
      recurrent cancers of the stomach (gastric cancer) with a combination of 
      immunotherapy and radiotherapy. The combination was able to control disease in a 
      subset of patients and was safe, with no obvious additional adverse effects when 
      adding radiotherapy. The median survival time-at which point half of the patients 
      treated are still alive-was 230 days. While these results are promising, larger, 
      more rigorous studies are needed to determine whether this combination therapy is 
      better than alternative approaches to treating advanced or recurrent gastric 
      cancers.
OABL- eng
COIS- K.K. reports speaker fee from ONO Pharmaceutical Co., Ltd. and Bristol-Myers 
      Squibb. The remaining authors declare no competing interests. ONO Pharmaceutical 
      Co., Ltd. and Bristol-Myers Squibb are not involved in the planning of study 
      design, progress of this study, data collection and analysis, interpretation of 
      results, and manuscript preparation.
EDAT- 2023/08/16 00:42
MHDA- 2023/08/16 00:43
PMCR- 2023/08/15
CRDT- 2023/08/15 23:36
PHST- 2023/03/07 00:00 [received]
PHST- 2023/08/04 00:00 [accepted]
PHST- 2023/08/16 00:43 [medline]
PHST- 2023/08/16 00:42 [pubmed]
PHST- 2023/08/15 23:36 [entrez]
PHST- 2023/08/15 00:00 [pmc-release]
AID - 10.1038/s43856-023-00343-4 [pii]
AID - 343 [pii]
AID - 10.1038/s43856-023-00343-4 [doi]
PST - epublish
SO  - Commun Med (Lond). 2023 Aug 15;3(1):111. doi: 10.1038/s43856-023-00343-4.