A Q&A with Al Musella, DPM, President, Musella Foundation For Brain Tumor Research & Information, Inc., Hewlett, NY; email: email@example.com, phone: 888-295-4740
Q: You direct an established foundation that supports research and information about brain tumors. What would you do if you yourself were diagnosed with a glioblastoma multiforme (GBM)?
A: Now that GBMs are in the news again, I would like to discuss what I would do if it happened to me—a newly diagnosed GBM in an adult in otherwise good shape. There are several choices.
Standard of care: Surgery, radiation, Temozolomide. Chance of 5 year survival is about 5%.
Standard of care PLUS Optune. Bumps my chance of 5 year survival up to 24.9% (if used over 90% of the time) with no added toxicity.
Phase 3 Clinical trials: There are now about nine phase 3 trials for newly diagnosed GBM. Some have impressive phase 1 and phase 2 data. By the time a treatment gets to phase 3, it has shown enough promise in earlier trials that the sponsor is willing to risk a lot of money to test in a phase 3 trial. Most have two big downsides: 1) Most have a control group of patients who receive the old standard of care so that some of the participants do not get the experimental treatment. 2) Most do not allow you to use Optune, so you are trading a known benefit for a chance at an unknown benefit.
“In a phase II trial funded by the European Organisation for Research and Treatment of Cancer and reported in The Lancet Oncology, van den Bent et al found no evidence of a survival benefit with the addition of bevacizumab (Avastin) to temozolomide in patients with a first recurrence of World Health Organization grade II or III glioma without the 1p/19q codeletion.
“In the open-label trial, conducted at 32 European centers, 155 patients were randomized between February 2011 and July 2015 to receive either temozolomide at 150 to 200 mg/m² on days 1 to 5 every 4 weeks for a maximum of 12 cycles (n = 77) or the same temozolomide regimen plus bevacizumab at 10 mg/kg every 2 weeks until disease progression (n = 78). Previous chemotherapy must have been stopped at least 6 months before enrollment, and radiotherapy, at least 3 months before enrollment. Overall, 44% of patients in the combination group and 47% in the temozolomide group had grade III disease.”
“A genetically modified poliovirus may help some patients fight a deadly form of brain cancer, researchers report.
“The experimental treatment seems to have extended survival in a small group of patients with glioblastoma who faced a grim prognosis because standard treatments had failed, Duke University researchers say.
” ‘I’ve been doing this for 50 years and I’ve never seen results like this,’ says Dr. Darell Bigner, the director emeritus of the The Preston Robert Tisch Brain Tumor Center at the Duke Cancer Institute, who is helping develop the treatment.”
“In a pilot study of recurrent glioma, 26% of patients treated with the optimal dose of vocimagene amiretroprepvec (aka Toca 511), a novel oncolytic virus therapy, achieved durable, long-term responses and remained alive 3 or more years later. This outcome far exceeded ‘historical benchmarks’ for this poor-prognosis population, according to lead researcher Bob S. Carter, MD, PhD, the William and Elizabeth Sweet Professor and Chief of Neurosurgery at Massachusetts General Hospital, Boston.”
“A new way of treating glioblastoma — the deadly brain tumor currently ailing Arizona Sen. John McCain — with a personalized vaccine is giving some patients in a clinical trial more time.
“The vaccination, called DCVax-L, is made out of a patient’s own cells and uses them to jumpstart the immune system and attack the tumor. In the trial, some patients survived for more than 36 months — more than a year and a half longer than current life expectancy after glioblastoma diagnosis.”
“MimiVax LLC, a clinical-stage biotechnology company developing immunotherapeutics and targeted therapies for cancer treatment, today announced positive interim results from a multicenter Phase II study of SurVaxM in patients with newly diagnosed glioblastoma (nGBM). These promising interim results support further development of SurVaxM in combination with standard therapy as a potential treatment for glioblastoma. A randomized trial of SurVaxM in glioblastoma is planned, pending completion of this study and review at the end of Q4 2018.”
“An Independent Data and Safety Monitoring Board (DSMB) unanimously recommended that the Phase 1/2 clinical trial evaluating VBI Vaccines’ VBI-1901 continue to enroll patients with recurrent glioblastoma (GBM) in a second study arm.
“The positive review recommended the study continue without modification, after scanning through all safety data from the first group of patients, who received the lowest VBI-1901 dose. Enrollment now has commenced for the second, intermediate-dose study arm.”
“Carboxyamidotriazole orotate (CTO) in combination with temozolomide (Temodar), with or without radiotherapy, produced positive safety and efficacy results in a phase Ib study of patients with glioblastoma (GBM) or anaplastic gliomas.
“Forty-two patients were divided into 2 cohorts and received treatment. Cohort 1 included 27 patients with recurrent, temozolomide-refractory anaplastic gliomas or GBM. Twenty-one patients were assigned to a regimen of 219 to 812.5 mg/m2 of once-daily CTO in escalating doses and 6 were assigned to a fixed daily dose of 600 mg of CTO. All 27 patients received 150 mg/m2 of temozolomide on days 1 to 5 of each 28-day cycle.”
“As immunotherapies continue to make up a larger share of new cancer drugs, researchers are looking for the most effective ways to use these cutting edge treatments in combination with each or with other pre-existing options. New studies from the Abramson Cancer Center of the University of Pennsylvania are providing fresh clues on potentially effective combinations with CAR T therapy in brain cancer as well as a novel therapeutic target in head and neck cancer, and also providing greater understanding of the mechanisms of resistance in pancreatic cancer. All three studies will be presented as late breaking abstracts at the American Association for Cancer Research Annual Meeting in Chicago.”