Bristol Myers Squibb Drug Ineffective for Recurrent Glioblastoma

Bristol Myer’s Squibb drug, nivolumab, did not improve overall survival compared with the drug bevacizumab in the treatment of recurrent glioblastoma in a phase 3 clinical trial, according to a recent study.

Recently published in JAMA Network Open, the randomized phase 3 clinical trial of 369 patients with recurrent glioblastoma treated with nivolumab did not meet the primary end point of overall survival.

But the safety profile of nivolumab in patients with glioblastoma was consistent with that in other tumor types.

Nivolumab is a fully human immunoglobulin G4 monoclonal antibody targeting the programmed death-1 immune checkpoint receptor, researchers said. 

Eligible patients were 18 years or older and had histologically confirmed World Health Organization grade IV recurrent glioblastoma or gliosarcoma after first-line treatment with radiotherapy and temozolomide.

Researchers randomized patients to receive nivolumab 3 mg/kg (184 patients) or bevacizumab 10 mg/kg (185 patients) every two weeks until confirmed disease progression, adverse effects, or death.

Tumor assessments were carried out using contrast-enhanced MRI at baseline, day 1 of weeks 7 and 13, and every 8 weeks following. Follow-up for survival was every 3 months.

The median OS was comparable between both nivolumab, and bevacizumab, at 9.8 months and 9.4 months, respectively. The 12-month OS was 42 percent in both groups. 

Nearly 175 of 184 patients (95 percent) in the nivolumab group and 158 of 185 patients (85 percent) in the bevacizumab group had permanently discontinued the treatment. The most common reason noted was disease progression.

Researchers stated that overall, glioblastoma has an extremely poor prognosis. Treatment options at recurrence are limited and no therapy has prolonged overall survival, which underscores the need for novel therapeutic interventions for patients.

The use of immunotherapy to promote antitumor immune response continues as an area of active research in the treatment of glioblastoma. 

“To our knowledge, the CheckMate 143 randomized clinical trial is the first phase 3 study investigating the use of a PD-1 inhibitor in patients with recurrent glioblastoma,” researchers explained. 

“The study did not meet the primary end point of overall survival. The safety profile of nivolumab in patients with glioblastoma was consistent with that in other tumor types,” they continued. “Patients with methylated MGMT promoter glioblastoma and no baseline corticosteroid use may potentially derive benefit from treatment with immune checkpoint inhibition.”

Although not notably effective against recurring glioblastoma, nivolumab was found to be effective in patients with advanced kidney cancer that had progressed after their initial treatment, soon after becoming the standard of care for these patients.

At the end of April, Bristol Myers and Exelixis released positive phase 3 clinical trial results evaluating nivolumab in combination with cabometyx for use against untreated kidney patients.

CheckMate-9ER met its endpoint of progression-free survival (PFS) at final analysis and the secondary endpoint of overall survival. The combination of cabozantinib plus nivolumab is beneficial in the key efficacy measures of progression-free survival and overall survival for previously untreated kidney cancer patients. 

Researchers stressed that if approved, the combination may become a vital new option for patients with metastatic renal cell carcinoma.

“The positive topline results from the Phase 3 CheckMate -9ER trial evaluating Opdivo in combination with CABOMETYX build on our understanding of Opdivo-based regimens, and we look forward to working with global health authorities to help bring this new combination regimen to previously untreated patients, a population that despite recent advances, remains in need of additional therapeutic options that extend survival,” Brian Lamon, PhD, development lead for genitourinary cancers at Bristol Myers Squibb, said in the announcement.