Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study
We evaluated the efficacy and safety of bevacizumab beyond progression (BBP) in Japanese patients with newly diagnosed glioblastoma and explored predictors of response to bevacizumab. This phase II study evaluated a protocol-defined primary therapy by radiotherapy with concurrent and adjuvant temozo...
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/22/5522 |
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| author | Motoo Nagane Koichi Ichimura Ritsuko Onuki Daichi Narushima Mai Honda-Kitahara Kaishi Satomi Arata Tomiyama Yasuhito Arai Tatsuhiro Shibata Yoshitaka Narita Takeo Uzuka Hideo Nakamura Mitsutoshi Nakada Yoshiki Arakawa Takanori Ohnishi Akitake Mukasa Shota Tanaka Toshihiko Wakabayashi Tomokazu Aoki Shigeki Aoki Soichiro Shibui Masao Matsutani Keisuke Ishizawa Hideaki Yokoo Hiroyoshi Suzuki Satoshi Morita Mamoru Kato Ryo Nishikawa |
| author_facet | Motoo Nagane Koichi Ichimura Ritsuko Onuki Daichi Narushima Mai Honda-Kitahara Kaishi Satomi Arata Tomiyama Yasuhito Arai Tatsuhiro Shibata Yoshitaka Narita Takeo Uzuka Hideo Nakamura Mitsutoshi Nakada Yoshiki Arakawa Takanori Ohnishi Akitake Mukasa Shota Tanaka Toshihiko Wakabayashi Tomokazu Aoki Shigeki Aoki Soichiro Shibui Masao Matsutani Keisuke Ishizawa Hideaki Yokoo Hiroyoshi Suzuki Satoshi Morita Mamoru Kato Ryo Nishikawa |
| author_sort | Motoo Nagane |
| collection | DOAJ |
| description | We evaluated the efficacy and safety of bevacizumab beyond progression (BBP) in Japanese patients with newly diagnosed glioblastoma and explored predictors of response to bevacizumab. This phase II study evaluated a protocol-defined primary therapy by radiotherapy with concurrent and adjuvant temozolomide plus bevacizumab, followed by bevacizumab monotherapy, and secondary therapy (BBP: bevacizumab upon progression). Ninety patients received the protocol-defined primary therapy (BBP group, <i>n</i> = 25). Median overall survival (mOS) and median progression-free survival (mPFS) were 25.0 and 14.9 months, respectively. In the BBP group, in which <i>O<sup>6</sup></i>-methylguanine-DNA methyltransferase (<i>MGMT</i>)-unmethylated tumors predominated, mOS and mPFS were 5.8 and 1.9 months from BBP initiation and 16.8 and 11.4 months from the initial diagnosis, respectively. The primary endpoint, the 2-year survival rate of the BBP group, was 27.0% and was unmet. No unexpected adverse events occurred. Expression profiling using RNA sequencing identified that Cluster 2, which was enriched with the genes involved in macrophage or microglia activation, was associated with longer OS and PFS independent of the <i>MGMT</i> methylation status. Cluster 2 was identified as a significantly favorable independent predictor for PFS, along with younger age and methylated <i>MGMT</i>. The novel expression classifier may predict the prognosis of glioblastoma patients treated with bevacizumab. |
| first_indexed | 2024-03-09T18:26:01Z |
| format | Article |
| id | doaj.art-0bd5bbbae8564ab29264e7e1066c5d9d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T18:26:01Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0bd5bbbae8564ab29264e7e1066c5d9d2023-11-24T07:52:33ZengMDPI AGCancers2072-66942022-11-011422552210.3390/cancers14225522Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker StudyMotoo Nagane0Koichi Ichimura1Ritsuko Onuki2Daichi Narushima3Mai Honda-Kitahara4Kaishi Satomi5Arata Tomiyama6Yasuhito Arai7Tatsuhiro Shibata8Yoshitaka Narita9Takeo Uzuka10Hideo Nakamura11Mitsutoshi Nakada12Yoshiki Arakawa13Takanori Ohnishi14Akitake Mukasa15Shota Tanaka16Toshihiko Wakabayashi17Tomokazu Aoki18Shigeki Aoki19Soichiro Shibui20Masao Matsutani21Keisuke Ishizawa22Hideaki Yokoo23Hiroyoshi Suzuki24Satoshi Morita25Mamoru Kato26Ryo Nishikawa27Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo 181-8611, JapanDepartment of Brain Disease Translational Research, Juntendo University Graduate School of Medicine, Tokyo 113-8421, JapanDivision of Bioinformatics, National Cancer Center Research Institute, Tokyo 104-0045, JapanDivision of Bioinformatics, National Cancer Center Research Institute, Tokyo 104-0045, JapanDivision of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo 104-0045, JapanDepartment of Diagnostic Pathology, National Cancer Center Hospital, Tokyo 104-0045, JapanDepartment of Brain Disease Translational Research, Juntendo University Faculty of Medicine, Tokyo 113-8421, JapanDivision of Cancer Genomics, National Cancer Center Research Institute, Tokyo 104-0045, JapanDivision of Cancer Genomics, National Cancer Center Research Institute, Tokyo 104-0045, JapanDepartment of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo 104-0045, JapanDepartment of Neurosurgery, Dokkyo Medical University, Tochigi 321-0293, JapanDepartment of Neurosurgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8555, JapanDepartment of Neurosurgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, JapanDepartment of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, JapanDepartment of Neurosurgery, Graduate School of Medicine, Ehime University, Ehime 790-0052, JapanDepartment of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, JapanDepartment of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, JapanDepartment of Neurosurgery, Graduate School of Medicine, Nagoya University, Aichi 464-8601, JapanDepartment of Neurosurgery, Kyoto Medical Center, Kyoto 612-8555, JapanDepartment of Radiology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, JapanDepartment of Neurosurgery, Teikyo University Hospital, Kawasaki 213-8507, JapanDepartment of Neurosurgery, Kurosawa Hospital, Gunma 370-1203, JapanDepartment of Pathology, Saitama Medical University, Saitama 350-0495, JapanDepartment of Human Pathology, Graduate School of Medicine, Gunma University, Gunma 371-8511, JapanDepartment of Pathology and Laboratory Medicine, National Hospital Organization Sendai Medical Center, Miyagi 983-8520, JapanDepartment of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, JapanDivision of Bioinformatics, National Cancer Center Research Institute, Tokyo 104-0045, JapanDepartment of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama 350-1298, JapanWe evaluated the efficacy and safety of bevacizumab beyond progression (BBP) in Japanese patients with newly diagnosed glioblastoma and explored predictors of response to bevacizumab. This phase II study evaluated a protocol-defined primary therapy by radiotherapy with concurrent and adjuvant temozolomide plus bevacizumab, followed by bevacizumab monotherapy, and secondary therapy (BBP: bevacizumab upon progression). Ninety patients received the protocol-defined primary therapy (BBP group, <i>n</i> = 25). Median overall survival (mOS) and median progression-free survival (mPFS) were 25.0 and 14.9 months, respectively. In the BBP group, in which <i>O<sup>6</sup></i>-methylguanine-DNA methyltransferase (<i>MGMT</i>)-unmethylated tumors predominated, mOS and mPFS were 5.8 and 1.9 months from BBP initiation and 16.8 and 11.4 months from the initial diagnosis, respectively. The primary endpoint, the 2-year survival rate of the BBP group, was 27.0% and was unmet. No unexpected adverse events occurred. Expression profiling using RNA sequencing identified that Cluster 2, which was enriched with the genes involved in macrophage or microglia activation, was associated with longer OS and PFS independent of the <i>MGMT</i> methylation status. Cluster 2 was identified as a significantly favorable independent predictor for PFS, along with younger age and methylated <i>MGMT</i>. The novel expression classifier may predict the prognosis of glioblastoma patients treated with bevacizumab.https://www.mdpi.com/2072-6694/14/22/5522bevacizumabglioblastomatemozolomideprogressionbiomarker |
| spellingShingle | Motoo Nagane Koichi Ichimura Ritsuko Onuki Daichi Narushima Mai Honda-Kitahara Kaishi Satomi Arata Tomiyama Yasuhito Arai Tatsuhiro Shibata Yoshitaka Narita Takeo Uzuka Hideo Nakamura Mitsutoshi Nakada Yoshiki Arakawa Takanori Ohnishi Akitake Mukasa Shota Tanaka Toshihiko Wakabayashi Tomokazu Aoki Shigeki Aoki Soichiro Shibui Masao Matsutani Keisuke Ishizawa Hideaki Yokoo Hiroyoshi Suzuki Satoshi Morita Mamoru Kato Ryo Nishikawa Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study Cancers bevacizumab glioblastoma temozolomide progression biomarker |
| title | Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study |
| title_full | Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study |
| title_fullStr | Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study |
| title_full_unstemmed | Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study |
| title_short | Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study |
| title_sort | bevacizumab beyond progression for newly diagnosed glioblastoma biomark phase ii safety efficacy and biomarker study |
| topic | bevacizumab glioblastoma temozolomide progression biomarker |
| url | https://www.mdpi.com/2072-6694/14/22/5522 |
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