PMID- 36729213
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 72
IP  - 6
DP  - 2023 Jun
TI  - Effect of genetic polymorphisms on outcomes following nivolumab for advanced 
      renal cell carcinoma in the SNiP-RCC trial.
PG  - 1903-1915
LID - 10.1007/s00262-023-03367-w [doi]
AB  - BACKGROUND: Anti-PD-1 antibodies are widely used for cancer treatment including 
      advanced renal cell carcinoma (RCC). However, their therapeutic and adverse 
      effects vary among patients. This study aimed to identify genetic markers that 
      predict outcome after nivolumab anti-PD-1 antibody treatment for advanced RCC. 
      METHODS: This study was registered on the website of the University Hospital 
      Medical Information Network (protocol ID, UMIN000037739). Patient enrollment was 
      conducted at 23 institutions in Japan between August 19, 2019, and September 30, 
      2020. Patient follow-up ended on March 31, 2021. Patients were treated with 
      nivolumab for advanced clear cell RCC. A genome-wide association study was 
      performed in the development set, while genotyping of target regions in the 
      validation set was undertaken. Single nucleotide polymorphisms (SNPs) in genes of 
      interest CD274, PDCD1LG2 and PDCD1 were genotyped in the combined set. The 
      primary endpoint was the association of SNPs with objective response following 
      nivolumab treatment. As secondary endpoints, the associations of SNPs with 
      radiographic progression-free survival (rPFS) and treatment-related grade  >/= 3 
      adverse events (AEs) were evaluated. RESULTS: A genome-wide association study 
      followed by a validation study identified that SNPs in FARP1 (rs643896 and 
      rs685736) were associated with objective response and rPFS but not AEs following 
      nivolumab treatment. Furthermore, SNPs in PDCD1LG2 (rs822339 and rs1411262) were 
      associated with objective response, rPFS, and AEs following nivolumab treatment. 
      Genetic risk category determined according to the number of risk alleles in SNPs 
      (rs643896 in FARP1 and rs4527932 in PDCD1LG2) excellently predicted objective 
      response and rPFS in nivolumab treatment. CONCLUSION: This study revealed that 
      SNPs in FARP1 and PDCD1LG2 were correlated with outcome in nivolumab treatment. 
      The use of these SNPs may be beneficial in selecting appropriate treatment for 
      individual patients and may contribute to personalized medicine.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Shiota, Masaki
AU  - Shiota M
AD  - Department of Urology, Graduate School of Medical Sciences, Kyushu University, 
      3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 
      shiota.masaki.101@m.kyushu-u.ac.jp.
FAU - Miyake, Hideaki
AU  - Miyake H
AD  - Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
FAU - Takahashi, Masayuki
AU  - Takahashi M
AD  - Department of Urology, Tokushima University Graduate School of Biomedical 
      Sciences, Tokushima, Japan.
FAU - Oya, Mototsugu
AU  - Oya M
AD  - Department of Urology, Keio University School of Medicine, Tokyo, Japan.
FAU - Tsuchiya, Norihiko
AU  - Tsuchiya N
AD  - Department of Urology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
FAU - Masumori, Naoya
AU  - Masumori N
AD  - Department of Urology, Sapporo Medical University School of Medicine, Sapporo, 
      Japan.
FAU - Matsuyama, Hideyasu
AU  - Matsuyama H
AD  - Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, 
      Japan.
FAU - Obara, Wataru
AU  - Obara W
AD  - Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan.
FAU - Shinohara, Nobuo
AU  - Shinohara N
AD  - Department of Renal and Genitourinary Surgery, Hokkaido University Graduate 
      School of Medicine, Sapporo, Japan.
FAU - Fujimoto, Kiyohide
AU  - Fujimoto K
AD  - Department of Urology, Nara Medical University, Kashihara, Japan.
FAU - Nozawa, Masahiro
AU  - Nozawa M
AD  - Department of Urology, Faculty of Medicine, Kindai University, Osaka, Japan.
FAU - Ohba, Kojiro
AU  - Ohba K
AD  - Department of Urology, Graduate School of Biomedical Sciences, Nagasaki 
      University, Nagasaki, Japan.
FAU - Ohyama, Chikara
AU  - Ohyama C
AD  - Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, 
      Japan.
FAU - Hashine, Katsuyoshi
AU  - Hashine K
AD  - Department of Urology, National Hospital Organization Shikoku Cancer Center, 
      Matsuyama, Ehime, Japan.
FAU - Akamatsu, Shusuke
AU  - Akamatsu S
AD  - Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan.
FAU - Kamba, Tomomi
AU  - Kamba T
AD  - Department of Urology, Graduate School of Medical Sciences, Kumamoto University, 
      Kumamoto, Japan.
FAU - Mita, Koji
AU  - Mita K
AD  - Department of Urology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan.
FAU - Gotoh, Momokazu
AU  - Gotoh M
AD  - Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Tatarano, Shuichi
AU  - Tatarano S
AD  - Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima 
      University, Kagoshima, Japan.
FAU - Fujisawa, Masato
AU  - Fujisawa M
AD  - Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
FAU - Tomita, Yoshihiko
AU  - Tomita Y
AD  - Department of Urology and Molecular Oncology, Graduate School of Medicine and 
      Dental Sciences, Niigata University, Niigata, Japan.
FAU - Mukai, Shoichiro
AU  - Mukai S
AD  - Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, 
      Japan.
FAU - Ito, Keiichi
AU  - Ito K
AD  - Department of Urology, National Defense Medical College, Saitama, Japan.
FAU - Tanegashima, Tokiyoshi
AU  - Tanegashima T
AD  - Department of Urology, Graduate School of Medical Sciences, Kyushu University, 
      3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
FAU - Tokunaga, Shoji
AU  - Tokunaga S
AD  - Medical Information Center, Kyushu University Hospital, Fukuoka, Japan.
FAU - Eto, Masatoshi
AU  - Eto M
AD  - Department of Urology, Graduate School of Medical Sciences, Kyushu University, 
      3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
CN  - SNiP-RCC investigators
LA  - eng
PT  - Journal Article
DEP - 20230202
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Humans
MH  - Nivolumab/therapeutic use
MH  - *Carcinoma, Renal Cell/drug therapy/genetics
MH  - Genome-Wide Association Study
MH  - Progression-Free Survival
MH  - Polymorphism, Single Nucleotide
MH  - *Kidney Neoplasms/drug therapy/genetics
PMC - PMC10992440
OTO - NOTNLM
OT  - Anti-PD-1 antibody
OT  - Genome-wide association study
OT  - Nivolumab
OT  - Renal cell carcinoma
OT  - Single nucleotide polymorphism
COIS- Hideaki Miyake received honoraria from Ono Pharmaceutical. Masayuki Takahashi 
      received honoraria from Ono Pharmaceutical and Bristol-Myers Squibb. Mototsugu 
      Oya received honoraria from Pfizer, Novartis, Bayer, MSD, Eisai, Ono 
      Pharmaceutical, Bristol-Myers Squibb, Takeda Pharmaceutical and Merck Biopharma. 
      Norihiko Tsuchiya received honoraria from Pfizer, Novartis, MSD, Eisai, 
      Bristol-Myers Squibb, Takeda Pharmaceutical and Merck Biopharma, and support for 
      attending meetings from Merck Biopharma. Naoya Masumori received honoraria from 
      MSD, Bristol-Myers Squibb, Takeda Pharmaceutical and Ono Pharmaceutical. Hideyasu 
      Matsuyama received grants from Janssen Pharma, Takeda Pharmaceutical, Baxter, 
      KyowaKirin and Sanofi, and honoraria from Janssen Pharma, AstraZeneca, Merck 
      Biopharma, Bayer, Astellas Pharma and Chugai. Wataru Obara received honoraria 
      from Ono Pharmaceutical, Merck Biopharma, Takeda Pharmaceutical and Astellas 
      Pharma. Nobuo Shinohara received grants from Ono Pharmaceutical, honoraria from 
      Ono Pharmaceutical and Bristol-Myers Squibb, and support for attending meetings 
      from Ono Pharmaceutical and Bristol-Myers Squibb. Masahiro Nozawa received 
      honoraria from Takeda Pharmaceutical. Shusuke Akamatsu received grants from 
      Astellas Pharma, AstraZeneca and Tosoh, and honoraria from Janssen Pharma, 
      AstraZeneca, Bayer, Astellas Pharma, Sanofi and Takeda Pharmaceutical. Tomomi 
      Kamba received honoraria from AstraZeneca and Merck Biopharma. Masatoshi Eto 
      received from grants from Ono Pharmaceutical, and honoraria from Ono 
      Pharmaceutical and Bristol-Myers Squibb. All other authors declare no conflicts 
      of interests to the current manuscript.
EDAT- 2023/02/03 06:00
MHDA- 2023/05/22 06:42
PMCR- 2023/02/02
CRDT- 2023/02/02 11:18
PHST- 2022/11/09 00:00 [received]
PHST- 2023/01/04 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/02/03 06:00 [pubmed]
PHST- 2023/02/02 11:18 [entrez]
PHST- 2023/02/02 00:00 [pmc-release]
AID - 10.1007/s00262-023-03367-w [pii]
AID - 3367 [pii]
AID - 10.1007/s00262-023-03367-w [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2023 Jun;72(6):1903-1915. doi: 
      10.1007/s00262-023-03367-w. Epub 2023 Feb 2.