Question

IMPORTANCE Clinical outcomes for glioblastoma remain poor. Treatment with immune checkpoint blockade has shown benefits in many cancer types. To our knowledge, data from a randomized phase 3 clinical trial evaluating a programmed death-1 (PD-1) inhibitor therapy for glioblastoma have not been reported. OBJECTIVE To determine whether single-agent PD-1 blockade with nivolumab improves survival in patients with recurrent glioblastoma compared with bevacizumab. DESIGN, SETTING, AND PARTICIPANTS In this open-label, randomized, phase 3 clinical trial, 439 patients with glioblastoma at first recurrence following standard radiation and temozolomide therapy were enrolled, and 369 were randomized. Patients were enrolled between September 2014 and May 2015. The median follow-up was 9.5 months at data cutoff of January 20, 2017. The study included 57 multicenter, multinational clinical sites. INTERVENTIONS Patients were randomized 1:1 to nivolumab 3 mg/kg or bevacizumab 10 mg/kg every 2 weeks until confirmed disease progression, unacceptable toxic effects, or death. MAIN OUTCOMES AND MEASURES The primary end point was overall survival (OS). RESULTS A total of 369 patients were randomized to nivolumab (n = 184) or bevacizumab (n = 185). The MGMT promoter was methylated in 23.4% (43/184; nivolumab) and 22.7% (42/185; bevacizumab), unmethylated in 32.1% (59/184; nivolumab) and 36.2% (67/185; bevacizumab), and not reported in remaining patients. At median follow-up of 9.5 months, median OS (MOS) was comparable between groups: nivolumab, 9.8 months (95% CI, 8.2-11.8); bevacizumab, 10.0 months (95% CI, 9.0-11.8); HR, 1.04 (95% CI, 0.83-1.30); P = .76. The 12-month OS was 42% in both groups. The objective response rate was higher with bevacizumab (23.1%; 95% CI, 16.7%-30.5%) vs nivolumab (7.8%; 95% CI, 4.1%-13.3%). Grade 3/4 treatment-related adverse events (TRAES) were similar between groups (nivolumab, 33/182 [18.1%]; bevacizumab, 25/165 [15.2%]), with no unexpected neurological TRAEs or deaths due to TRAES. CONCLUSIONS AND RELEVANCE Although the primary end point was not met in this randomized clinical trial, mos was comparable between nivolumab and bevacizumab in the overall patient population with recurrent glioblastoma. The safety profile of nivolumab in patients with glioblastoma was consistent with that in other tumor types. TRIAL REGISTRATION Clinical Trials.gov Identifier: NCT02017717

Identify the scientific premise, main hypothesis addressed by the paper and the research question of the paper

Also, what is the main results and the implication of results

Answer 1

Scientific premise

To identify single-agent-PD-1 blockade with nivolumab as a richer and better treatment for patients with recurrent glioblastoma to make it possible to improve survival; this for use of the treatment instead of the current bevacizumab.

Hypothesis single-agent-PD-1 blockade with nivolumab will serve as a treatment and inmunotheraphy for patients with recurrent glioblastoma will improve the overall survival for patients with this disease, will meet safety and efficacy analysisi and the primary end point of OS improvement when compared to bevacizumab treatment.

Research question Does programmed cell deach 1 inmune checkpoint inhibition with nivolumab improve overall survival compared with bevacizumab treatment for patients with recurrent glioblastoma?

Main results The main results stated in the results of the research with a randomized phase-3 clinical trial of 369 patients with recurrent glioblastoma treated with nivolumab (184 treated with nivolumab) were found that overall survival benefits and improvements were not observed compared to patients with bevacizumab treatment (a total of 185).

Implication

Overall results can state that the treatment will replace the bevacizumab treatment. Clinical outcomes for glioblastoma remain poor.; further studies and research are need to be made to identify it as a secure and effective option, such as the nivolumab in combination with radiotherapy and temozolomide for newly diagnozed glioblastoma patients.