Presurgical Opdivo May Benefit Patients with Glioblastoma

Administration of Opdivo (nivolumab) before surgical resection in patients with glioblastoma appeared safe and feasible, according to phase 2 trial results published in Nature Medicine.

“Glioblastoma is the most common form of brain cancer. Its prognosis remains dismal. Unfortunately, the standard first-line treatment of surgery and chemoradiation has limited efficacy,” according to a summary by the American Association for Cancer Research (AACR). “Immune checkpoint blockade has been a promising therapeutic strategy in many cancers, including melanoma and lung cancer.”

Therefore, in the single-arm phase 2 trial, the researchers evaluated the feasibility, safety and immunobiological effects of Opdivo, a PD-1 blockade, given before and after surgery in 30 patients with glioblastoma. In total, 27 underwent salvage surgeries for recurrent cases and three patients had primary surgery for newly diagnosed disease.

In 18 patients, complete or nearly complete tumor resection was achieved and in the remaining 11 patients, partial tumor resection occurred.

Treatment with Opdivo appeared well-tolerated and only one patient experienced a grade 2 immune-related side effect while another patient experienced grade 2 hyperthyroidism. In addition, two patients had bleeding episodes after treatment with neoadjuvant Opdivo while waiting for surgery, which required advancing the date of the surgery in one patient.

Median progression-free survival — or the time from treatment to disease worsening – in evaluable patients was 4.1 months and the median overall survival was 7.3 months. Of note, three patients remained alive after long-term follow-up. “The length of progression-free and overall survival found in the study for recurrent cases is comparable to previous reports, but the limited sample size prevents definitive conclusions about the clinical impact of treatment,” the researchers wrote.

Two patients achieved complete resection in the primary surgery during the trial and remained disease-free for more than 33.3 and 28.5 months, respectively, and one relapsed four months after salvage resection but remained alive following response to subsequent Avastin (bevacizumab) treatment, which warrants further investigation, the researchers added.

“Although the number of patients treated was not big enough to make definitive conclusions about the survival benefit of the treatment, the (researchers) observed that the PD-1 inhibitor induced a more diverse population of the immune cells called T cells at the tumor site,” the AACR wrote.

“A more diverse T cell population is a sign of an effective immune system,” the organization added. “In light of the positive effects of a PD-1 inhibitor on the immune system even when given as a single-agent and given before surgery, (the researchers) anticipate that combining anti-PD-1 inhibitors with other immunotherapies can bring us one step closer to effectively treating glioblastoma patients.”