Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study.


Journal

International journal of clinical oncology
ISSN: 1437-7772
Titre abrégé: Int J Clin Oncol
Pays: Japan
ID NLM: 9616295

Informations de publication

Date de publication:
Dec 2021
Historique:
received: 30 03 2021
accepted: 07 09 2021
pubmed: 30 9 2021
medline: 16 11 2021
entrez: 29 9 2021
Statut: ppublish

Résumé

An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma. Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%. Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27-66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4-17.7) and 1.5 (1.4-1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3-4 and 2.0% for Grade 5; most adverse events resolved and were manageable. The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types. JapicCTI-152967.

Sections du résumé

BACKGROUND BACKGROUND
An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma.
METHODS METHODS
Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%.
RESULTS RESULTS
Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27-66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4-17.7) and 1.5 (1.4-1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3-4 and 2.0% for Grade 5; most adverse events resolved and were manageable.
CONCLUSIONS CONCLUSIONS
The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types.
CLINICAL TRIAL REGISTRATION BACKGROUND
JapicCTI-152967.

Identifiants

pubmed: 34586548
doi: 10.1007/s10147-021-02028-1
pii: 10.1007/s10147-021-02028-1
pmc: PMC8580927
doi:

Substances chimiques

Nivolumab 31YO63LBSN

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2205-2215

Informations de copyright

© 2021. The Author(s).

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Auteurs

Tomokazu Aoki (T)

Department of Neurosurgery, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihatacho, Fushimi Ward, Kyoto, 612-8555, Japan. totorolangdom@yahoo.co.jp.

Naoki Kagawa (N)

Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Kazuhiko Sugiyama (K)

Department of Clinical Oncology and Neuro-Oncology Program, Hiroshima University Hospital, Hiroshima, Japan.

Toshihiko Wakabayashi (T)

Department of Neurosurgery, Nagoya University Hospital, Nagoya, Japan.

Yoshiki Arakawa (Y)

Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Shigeru Yamaguchi (S)

Department of Neurosurgery, Hokkaido University Hospital, Hokkaido, Japan.

Shota Tanaka (S)

Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan.

Eiichi Ishikawa (E)

Department of Neurosurgery, University of Tsukuba Hospital, Ibaraki, Japan.

Yoshihiro Muragaki (Y)

Department of Neurosurgery, Tokyo Women's Medical University Hospital, Tokyo, Japan.

Motoo Nagane (M)

Faculty of Medicine, Department of Neurosurgery, Kyorin University, Tokyo, Japan.

Mitsutoshi Nakada (M)

Department of Neurosurgery, Kanazawa University Hospital, Kanazawa, Japan.

Satoshi Suehiro (S)

Department of Neurosurgery, Ehime University Hospital, Ehime, Japan.

Nobuhiro Hata (N)

Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Junichiro Kuroda (J)

Department of Neurosurgery, Kumamoto University Hospital, Kumamoto, Japan.

Yoshitaka Narita (Y)

Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.

Yukihiko Sonoda (Y)

Department of Neurosurgery, Yamagata University Hospital, Yamagata, Japan.

Yasuo Iwadate (Y)

Department of Neurological Surgery, Chiba University Hospital, Chiba, Japan.

Manabu Natsumeda (M)

Department of Neurosurgery, Niigata University Medical and Dental Hospital, Niigata, Japan.

Yoichi Nakazato (Y)

Hidaka Center for Pathologic Diagnosis and Research, Hidaka Hospital, Gunma, Japan.

Hironobu Minami (H)

Department Medical Oncology/Hematology, Kobe University, Kobe, Japan.

Yuki Hirata (Y)

Oncology Early Clinical Development Planning, Ono Pharmaceutical Co., Ltd, Osaka, Japan.

Shunsuke Hagihara (S)

Department of Statistical Analysis, Ono Pharmaceutical Co., Ltd, Osaka, Japan.

Ryo Nishikawa (R)

Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan.

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