Advancing Glioblastoma Research Through a Phase 3 Niraparib Trial
Season 1, Episode 128, Sep 23, 12:00 PM
Investigators of the Gliofocus trial look to set a clinically relevant “benchmark” in the glioblastoma field, according to Nader Sanai, MD.
In a conversation with CancerNetwork®, Nader Sanai, MD discussed the current state of the glioblastoma field, highlighting ongoing research efforts to help improve outcomes among patients with this disease.
Sanai is the director of the Ivy Brain Tumor Center and J.N Harber Professor of Neurological Surgery, Francis and Dionne Najafi chair for Neurosurgical Oncology, and chief of neurological oncology at Barrow Neurological Institute.
Specifically, Sanai described plans to assess treatment with niraparib (Zejula) compared with temozolomide (Temodar) in a population of patients with newly diagnosed MGMT unmethylated glioblastoma as part of the phase 3 Gliofocus study (NCT06388733).1 He contextualized the rationale for conducting this study by focusing on findings from a proof-of-concept hybrid study (NCT05076513) and detailing how they supported additional investigation into the utility of niraparib.
According to findings from this proof-of-concept study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the median overall survival (OS) was 20.3 months among patients who received niraparib in combination with radiotherapy.2 Additionally, data showed that niraparib reached drug concentrations in Gadolinium-nonenhancing newly diagnosed glioblastoma tissue exceeding those of any other evaluated PARP inhibitors; investigators identified no new safety signals after combining niraparib with radiotherapy in this population.
With the Gliofocus trial, Sanai and co-investigators aim to provide a clinically meaningful quality of life benefit with niraparib-based therapy beyond a marginally valuable statistical advantage. By evaluating treatment with niraparib, investigators look to improve historical survival rates reported with standard-of-care options among patients with unmethylated disease.
“What we’re looking to do with this trial is set a benchmark that’s clinically relevant for patients and providers. The [OS] target for the study is 18 months, which is to effectively convert [a] 12-month natural history to a natural history closer to the methylated glioblastoma population,” Sanai said. “We think that is a meaningful transformation of a difficult patient population, a significant chunk of survival time that would be beneficial to patients, providers, and caregivers. Importantly, [it may also mean] an advantage for quality of life, which is of paramount importance for this patient population.”
References
1. A study comparing niraparib with temozolomide in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma. ClinicalTrials.gov. Updated June 24, 2024. Accessed September 16, 2024. https://tinyurl.com/y25er8p9
2. Sanai N, Umemura Y, Margaryan T, et al. Niraparib efficacy in patients with newly-diagnosed glioblastoma: Clinical readout of a phase 0/2 "trigger" trial. J Clin Oncol. 2024;42(suppl 16):2002. doi:10.1200/JCO.2024.42.16_suppl.2002
Sanai is the director of the Ivy Brain Tumor Center and J.N Harber Professor of Neurological Surgery, Francis and Dionne Najafi chair for Neurosurgical Oncology, and chief of neurological oncology at Barrow Neurological Institute.
Specifically, Sanai described plans to assess treatment with niraparib (Zejula) compared with temozolomide (Temodar) in a population of patients with newly diagnosed MGMT unmethylated glioblastoma as part of the phase 3 Gliofocus study (NCT06388733).1 He contextualized the rationale for conducting this study by focusing on findings from a proof-of-concept hybrid study (NCT05076513) and detailing how they supported additional investigation into the utility of niraparib.
According to findings from this proof-of-concept study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the median overall survival (OS) was 20.3 months among patients who received niraparib in combination with radiotherapy.2 Additionally, data showed that niraparib reached drug concentrations in Gadolinium-nonenhancing newly diagnosed glioblastoma tissue exceeding those of any other evaluated PARP inhibitors; investigators identified no new safety signals after combining niraparib with radiotherapy in this population.
With the Gliofocus trial, Sanai and co-investigators aim to provide a clinically meaningful quality of life benefit with niraparib-based therapy beyond a marginally valuable statistical advantage. By evaluating treatment with niraparib, investigators look to improve historical survival rates reported with standard-of-care options among patients with unmethylated disease.
“What we’re looking to do with this trial is set a benchmark that’s clinically relevant for patients and providers. The [OS] target for the study is 18 months, which is to effectively convert [a] 12-month natural history to a natural history closer to the methylated glioblastoma population,” Sanai said. “We think that is a meaningful transformation of a difficult patient population, a significant chunk of survival time that would be beneficial to patients, providers, and caregivers. Importantly, [it may also mean] an advantage for quality of life, which is of paramount importance for this patient population.”
References
1. A study comparing niraparib with temozolomide in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma. ClinicalTrials.gov. Updated June 24, 2024. Accessed September 16, 2024. https://tinyurl.com/y25er8p9
2. Sanai N, Umemura Y, Margaryan T, et al. Niraparib efficacy in patients with newly-diagnosed glioblastoma: Clinical readout of a phase 0/2 "trigger" trial. J Clin Oncol. 2024;42(suppl 16):2002. doi:10.1200/JCO.2024.42.16_suppl.2002