Enhanced molecular understanding of primary brain tumors has driven recent advances in treatment, which have extended beyond chemotherapy and radiotherapy to include immunomodulatory agents and electromagnetic fields applied directly to the scalp. Andrew B. Lassman, MD, Chief, Division of Neuro-Oncology, Columbia University Medical Center, New York, NY, provided an overview of the latest developments in the treatment of brain tumors at the 2016 American Academy of Neurology annual meeting.
Chemotherapy plus Radiotherapy Prolongs Survival in Patients with Grade II Gliomas
The recent publication of the 20-year-old, phase 3 clinical trial RTOG (Radiation Therapy Oncology Group) 9802 has shown, for the first time, that the addition of chemotherapy to radiotherapy prolonged survival for patients with low-grade gliomas, reported Dr Lassman. The RTOG 9802 clinical trial enrolled patients with World Health Organization grade II gliomas after maximal safe surgical resection.
Patients aged >40 years or with postoperative residual disease were randomized to receive radiotherapy (the control arm) or radiotherapy, followed by chemotherapy with the combination of procarbazine, lomustine, and vincristine (chemotherapy arm). The long-term follow-up results demonstrated that patients in the chemotherapy arm, on average, survived nearly twice as long as those in the control arm (median, 13.3 vs 7.8 years).
“All histologic subgroups appeared to benefit, but those with oligodendrogliomas benefited most. Efforts are underway to identify molecular factors that were prognostic of improved survival regardless of treatment, and predictive of benefit with procarbazine, lomustine, and vincristine,” Dr Lassman noted.
Bevacizumab Fails to Prolong Survival in Glioblastoma
Several nonrandomized clinical trials had suggested that bevacizumab (Avastin), an antibody targeting tumor vasculature, may be beneficial in patients with glioblastoma that worsened despite standard first-line therapy. Three recent randomized clinical trials, however, have failed to demonstrate a survival benefit from the addition of bevacizumab to standard first-line therapy with radiotherapy and temozolomide (Temodar).
Nevertheless, all 3 studies demonstrated that patients who received bevacizumab had longer progression-free survival compared with patients who did not receive bevacizumab, Dr Lassman reported.
“Given the absence of survival benefit, it remains controversial whether the benefit of prolonged tumor control justifies the potential toxicity and high cost of bevacizumab therapy,” said Dr Lassman.
Although there are other drugs that also target tumor vasculature, or antiangiogenic therapy, none to date has proved superior to bevacizumab, Dr Lassman observed.
Several different immunotherapies have shown promise against glioblastoma in early-stage clinical trials, including some that have produced long-lasting responses in patients with advanced disease. At least 3 immunotherapies are in phase 3 clinical trials.
Among the immunotherapies being studied are antitumor vaccines, including rindopepimut, a so-called peptide vaccine. The mature phase 2 clinical trial ReACT randomized patients with EGFRvIII mutation and recurrent glioblastoma to bevacizumab and rindopepimut or to bevacizumab and control treatment. Patients in the rindopepimut group had longer survival than patients in the control group (median, 11.3 months vs 9.3 months, respectively). A phase 3 randomized clinical trial for newly diagnosed glioblastoma with EGFRvIII mutation has completed accrual, and the results are pending.
Another approach to treating brain tumors involves the use of a portable device that patients wear on their scalp to deliver low-intensity, intermediate-frequency electric fields to gliomas.
A phase 3 clinical trial randomized patients with newly diagnosed glioblastoma to standard radiotherapy and temozolomide; or to radiotherapy, temozolomide, and tumor-treating fields after the completion of radiotherapy.
Interim analysis demonstrated superior results with radiotherapy plus temozolomide and tumor-treating fields compared with temozolomide plus radiotherapy alone with regard to progression-free survival (median, 7.1 months vs 4 months, respectively) and overall survival (median, 20.5 months vs 15.6 months, respectively).
Despite these outcomes, it remains unclear whether tumor-treating fields will become widely adapted, particularly because of “the logistics involved in device application and maintenance, the aesthetics associated with constant head-shaving required for device usage, and the optics of wearing the device,” said Dr Lassman.