Unveiling the Potential of Combined Therapies for Glioblastoma

The NAVAL trial (NCT03452579) investigated the effectiveness of combining the immunotherapy nivolumab (Opdivo) with different doses of the anti-angiogenic therapy bevacizumab (Avastin) in treating recurrent glioblastoma (rGBM). Previous studies have shown limited success with immunotherapy alone for this aggressive brain cancer.

The trial compared a standard dose and a lower dose of bevacizumab in combination with nivolumab. While overall survival and progression-free survival were similar between the 2 groups, post hoc analysis suggested a potential benefit for older patients in the standard-dose group.

Interestingly, the study found that the standard dose of bevacizumab led to a stronger immune response and reduced immunosuppressive cells. These findings suggest that combining immunotherapy with specific anti-angiogenic strategies might be a promising approach for treating rGBM.

The most common adverse effects were fatigue, proteinuria, diarrhea, hypertension, and increased lipase levels.

Here, Manmeet Ahluwalia, MD, deputy director, chief scientific officer, chief of solid tumor medical oncology, and Fernandez Family Foundation Endowed Chair in Cancer Research, Miami Cancer Institute, part of Baptist Health South Florida, discusses the trial.

Transcription:

0:05 | Glioblastoma is one of the most common primary brain tumors that we see in the United States. Unfortunately, the outcomes of this patient population are fairly dismal. Despite all the advances in radiation, chemotherapy, and surgery, an average survival of 15 to 18 months. All of our patients tend to occur around 6 to 9 months after diagnosis. And there is not even a single therapy that has been approved with any survival benefit in recurrent glioblastoma. So this trial, we focused in finding a combination of nivolumab and vevacizumab in this patient population. This was a randomized trial looking at nivolumab with the standard dose of bevacizumab vs low dose of bevacizumab.

0:50 | So this was a 90-patient study. There was 1:1 randomization 45 patients in each arm. Half the patients got nivolumab at standard dose along with bevacizumab at standard dose. Half the patients got nivolumab in standard dose but bevacizumab at a reduced dose of 3 mg/kg. Unfortunately, this study did not meet his primary end point. The overall survival at 12 months was close to 40% in both the arms, which was comparable to what we have seen with either bevacizumab alone or nivolumab alone.

1:24 | So in this randomized trial, when we looked at nivolumab along with bevacizumab, either at standard dose or low dose, we did not identify any new toxicity that is not previously known. Whatever the toxicity was was in alignment with what we have seen in other trials with this combination, or independently each drug, so no new toxicities or signals were identified.