PMID- 33262133
OWN - NLM
STAT- MEDLINE
DCOM- 20220120
LR  - 20231213
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 27
IP  - 4
DP  - 2021 Feb 15
TI  - Multicenter Phase I/II Study of Nivolumab Combined with Paclitaxel Plus 
      Ramucirumab as Second-line Treatment in Patients with Advanced Gastric Cancer.
PG  - 1029-1036
LID - 10.1158/1078-0432.CCR-20-3559 [doi]
AB  - PURPOSE: We conducted a phase I/II study to investigate the safety and efficacy 
      of nivolumab with paclitaxel plus ramucirumab. PATIENTS AND METHODS: Patients 
      with advanced gastric cancer (AGC) refractory to first-line chemotherapy were 
      included. Patients received nivolumab (3 mg/kg on days 1 and 15) combined with 
      paclitaxel (80 mg/m(2) on days 1, 8, and 15) and ramucirumab (8 mg/kg on days 1 
      and 15) every 4 weeks. After feasibility evaluation in six patients (phase I), 37 
      additional patients were enrolled in the phase II part with the primary endpoint 
      of 6-month progression-free survival (PFS) rate with two-sided 80% confidence 
      interval (CI). The combined positive score (CPS) was defined as the number of 
      programmed death-ligand 1-positive cells divided by the total number of viable 
      tumor cells multiplied by 100. RESULTS: Forty-three patients were enrolled. Of 
      these, 60.5% had CPS >/= 1. Dose-limiting toxicities were observed in two patients, 
      and the recommended dose was determined as level 1. Thirty-nine (90.7%) patients 
      experienced treatment-related adverse events (AEs) grade >/=3 and 14 (32.6%) 
      patients experienced immune-related AEs grade >/=3. The overall response rate was 
      37.2% (95% CI, 23.0%-53.5%) and the 6-month PFS rate was 46.5% (80% CI, 
      36.4%-55.8%; P = 0.067). Median survival time was 13.1 months (95% CI, 8.0-16.6 
      months): 13.8 months (95% CI, 8.0-19.5 months) in patients with CPS >/= 1 and 8.0 
      months (95% CI, 4.8-24.1 months) in patients with CPS < 1. CONCLUSIONS: Nivolumab 
      with paclitaxel plus ramucirumab demonstrated promising antitumor activity with 
      manageable toxicities as second-line treatment for AGC.
CI  - (c)2020 American Association for Cancer Research.
FAU - Nakajima, Takako Eguchi
AU  - Nakajima TE
AD  - Department of Clinical Oncology, St. Marianna University School of Medicine, 
      Kawasaki, Kanagawa, Japan. tnakajima@kuhp.kyoto-u.ac.jp.
AD  - Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy, 
      Kyoto University Hospital, Kyoto City, Kyoto, Japan.
FAU - Kadowaki, Shigenori
AU  - Kadowaki S
AD  - Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, 
      Japan.
FAU - Minashi, Keiko
AU  - Minashi K
AD  - Department of Clinical Trial Promotion, Chiba Cancer Center, Chuo, Chiba, Japan.
FAU - Nishina, Tomohiro
AU  - Nishina T
AD  - Department of Gastrointestinal Medical Oncology, National Hospital Organization 
      Shikoku Cancer Center, Matsuyama, Ehime, Japan.
FAU - Yamanaka, Takeharu
AU  - Yamanaka T
AD  - Department of Biostatistics, Yokohama City University School of Medicine, 
      Yokohama, Kanagawa, Japan.
FAU - Hayashi, Yuichiro
AU  - Hayashi Y
AD  - Division of Pathology, Keio University School of Medicine, Shinjuku, Tokyo, 
      Japan.
FAU - Izawa, Naoki
AU  - Izawa N
AD  - Department of Clinical Oncology, St. Marianna University School of Medicine, 
      Kawasaki, Kanagawa, Japan.
FAU - Muro, Kei
AU  - Muro K
AD  - Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, 
      Japan.
FAU - Hironaka, Shuichi
AU  - Hironaka S
AUID- ORCID: 0000-0001-9714-231X
AD  - Department of Clinical Trial Promotion, Chiba Cancer Center, Chuo, Chiba, Japan.
AD  - Department of Medical Oncology and Hematology, Oita University Faculty of 
      Medicine, Oita, Japan.
FAU - Kajiwara, Takeshi
AU  - Kajiwara T
AD  - Department of Gastrointestinal Medical Oncology, National Hospital Organization 
      Shikoku Cancer Center, Matsuyama, Ehime, Japan.
FAU - Kawakami, Yutaka
AU  - Kawakami Y
AD  - Division of Cellular Signaling, Institute for Advanced Medical Research, Keio 
      University School of Medicine, Shinjuku, Tokyo, Japan.
AD  - Department of Immunology, International University of Health and Welfare School 
      of Medicine, Narita, Chiba, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20201201
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 31YO63LBSN (Nivolumab)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nivolumab/*administration & dosage/adverse effects
MH  - Paclitaxel/*administration & dosage/adverse effects
MH  - Progression-Free Survival
MH  - Stomach Neoplasms/diagnosis/*drug therapy/mortality/pathology
MH  - Ramucirumab
EDAT- 2020/12/03 06:00
MHDA- 2022/01/21 06:00
CRDT- 2020/12/02 05:24
PHST- 2020/09/09 00:00 [received]
PHST- 2020/10/27 00:00 [revised]
PHST- 2020/11/25 00:00 [accepted]
PHST- 2020/12/03 06:00 [pubmed]
PHST- 2022/01/21 06:00 [medline]
PHST- 2020/12/02 05:24 [entrez]
AID - 1078-0432.CCR-20-3559 [pii]
AID - 10.1158/1078-0432.CCR-20-3559 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2021 Feb 15;27(4):1029-1036. doi: 10.1158/1078-0432.CCR-20-3559. 
      Epub 2020 Dec 1.