Sen. John McCain's diagnosis announced on same day as new brain tumor therapy

July 20, 2017 was a red-letter day for glioblastoma. On that day, Sen. John McCain’s (R-AZ) diagnosis of glioblastoma (GBM) made headlines. In less publicized news, a small clinical trial reported an important advancement in immunotherapy treatment for GBM.

In reference to Sen. McCain, Alex B. Valadka, MD, President of the American Association of Neurological Surgeons (AANS), stated, "While a cure remains elusive, with the availability of more aggressive and targeted treatments, there has never been a more hopeful time for improving the quality of life and life expectancy for patients experiencing this dreaded disease."

Recovering "Amazingly Well"

The Mayo Clinic Hospital in Phoenix, AZ, where the 80-year-old senator was treated, released few specific details. What is known is that his glioblastoma was associated with a blood clot above his left eye and that surgeons performed a minimally invasive craniotomy with an eyebrow incision.

"Scanning done since the procedure … shows that the tissue of concern was completely resected by imaging criteria," the hospital announced. "The Senator's doctors say he is recovering from his surgery 'amazingly well' and his underlying health is excellent."

Just over a week after his procedure, Sen. McCain was back in Washington, DC. In the wee hours of July 28, during the Senate debate over the "skinny repeal" of parts of the Affordable Care Act, Sen. McCain cast the decisive vote—a wordless thumbs-down—against the proposed legislation.

"He looked good—he's walking around, he's talking. His neurological performance status is high," observed neurosurgeon Donald M. O'Rourke, MD, Associate Professor of Neurosurgery at the University of Pennsylvania's the Perelman School of Medicine, in Philadelphia, PA. "So it looks like he's going to be in good shape for treatment."

At press time, Sen. McCain's office reported that the Senator has returned to Arizona to undergo further treatment at Mayo Clinic: "On Monday, July 31, he will begin a standard post-surgical regimen of targeted radiation and chemotherapy. During that time, Senator McCain will maintain a work schedule. He plans to return to Washington at the conclusion of the August recess."

Dr. O'Rourke, who is not involved in the Senator's case, said, "The treatment in a vigorous guy like that may not be that problematic for him, because radiation is typically a very short daily session and the chemotherapy pill that's taken together with that doesn't have much in the way of side effects."

Recurrence and Investigational Treatment

Many patients do well initially after tumor resection, Dr. O'Rourke noted. "But the biggest problem with glioblastoma is recurrence," he added. "It is an inevitable feature of this disease."

For the average patient with GBM, life expectancy is currently about 15 to 18 months, he estimated. "So I think what John McCain will probably do—as everyone educated on this does—is to go around and try to get some opinions regarding experimental care. This wouldn't replace the chemotherapy radiation strategy, but add to that in the hope of trying to limit and prolong the time for recurrence," Dr. O'Rourke speculated.

To that end, Dr. O'Rourke and other groups of researchers are looking for ways to stave off recurrence, or prevent it altogether. "There's a push for precision medicine and personalized approaches, and in immuno-oncology—which is what we're pursuing here at Penn—we're utilizing personalized T cells."

In a paper published the same day that Sen. McCain's diagnosis was announced, Dr. O'Rourke, Marcela Maus, MD, PhD, and colleagues reported results of a personalized T cell immunotherapy treatment in a small cohort of patients with refractory GBM. They showed that engineered T cells, administered intravenously, can enter the brain, go to the site of the tumor, become active and divide, and actually reduce the target antigen.

To read an interview on this topic with Marcela Maus, MD, PhD, click here.

"It is a very prevalent mutation that's seen in about 30% of glioblastomas, and there's a lot of data that indicates that it drives the tumor phenotype," Dr. O'Rourke said.

However, the research needs to overcome at least a couple large hurdles before it is deemed a clinical breakthrough in immunotherapy. So, as an experimental phase 1 clinical trial, this treatment may not be appropriate for a newly-diagnosed patient such as Sen. McCain.

Nevertheless, it's a still a major finding. "This is the first strategy in my professional career that I think will ultimately lead to long-term remission in this disease. I don't know when that will be, but I think it will occur through an approach along these lines," Dr. O'Rourke said, being careful to avoid overhyping the results. "There's a degree of excitement now in immune-oncology that there hasn't been with cancer care in my career over the last two or three decades."