Multiple Treatment Options for Sen. John McCain's Glioblastoma

Alicia Ault

July 20, 2017

Senator John McCain — potentially a key vote on the proposal to repeal or replace the Affordable Care Act (ACA) — has been diagnosed with glioblastoma multiforme.

The Arizona Republican underwent a minimally invasive craniotomy on July 14 to remove a blood clot above his left eye, and subsequent pathology determined that the clot was associated with glioblastoma, according to a statement from the Mayo Clinic, where McCain had the surgery.

Scans show the tumor was completely resected, and treatment options may include a combination of chemotherapy and radiation, according to the clinic statement, which characterized McCain's underlying health as excellent.

It is unlikely that the glioblastoma — which is a primary tumor — is related to McCain's history of melanoma, according to the statement.

McCain's initial surgery was given as the reason why Senate majority leader Mitch McConnell postponed a vote on the Better Care Reconciliation Act. McConnell has said he is still considering a vote on a repeal of the ACA the week of July 24, but McCain's diagnosis throws that into question.

It is the second time that glioblastoma has inserted itself at a pivotal time in the history of the ACA. Senator Ted Kennedy was diagnosed with glioblastoma in May 2008 and did not work for the first 6 months while he received treatment. Coming back to the US Capitol after President Barack Obama's election, Kennedy, despite his cancer and quickly failing health, was a vocal advocate for the push to get the ACA passed.

Beau Biden — son of former vice president Joe Biden and the inspiration for the Cancer Moonshot — also had glioblastoma. He died in May 2015 at age 46.

Most Aggressive

Kennedy lived 15 months after his diagnosis, putting him squarely on the median for survival for glioblastoma multiforme, the most common and most aggressive of the gliomas, according to Keith Black, MD, chairman and professor of neurosurgery at the Cedars-Sinai Medical Center, Los Angeles, California, who spoke with Medscape Medical News shortly after the legislator's death in August 2009.

Gliomas include grade 1 and 2 tumors that are regarded as precancerous, although about 70% become malignant; grade 3 anaplastic astrocytomas; and grade 4 glioblastomas.

About 26,000 primary malignant brain tumors are diagnosed each year in the United States, of which 15% are glioblastomas, according to the American Brain Tumor Association (ABTA). Glioblastomas account for the largest number of malignant tumors, with an estimated 12,390 new cases predicted in 2017, said that ABTA. Symptoms can include headache, seizures, sensory disturbances, personality or memory changes, fatigue, nausea, and vomiting.

The recurrence rate for glioblastomas after treatment is near 100%, with an average time to recurrence of 6 to 7 months, according to John DeGroot, MD, professor of Neuro-Oncology, the University of Texas MD Anderson Cancer Center in Houston.

CAR T as a Potential Treatment?

Treatment for glioblastoma has not changed much since Kennedy's death, although new possibilities — primarily immunotherapy and  chimeric antigen receptor (CAR) T-cell therapy — are being explored.

Two chemotherapy regimens have been the standard for glioblastoma: temozolomide (Temodar, Schering) and the Gliadel wafer (polifeprosan with carmustine implant). Temozolomide has been more commonly used. It is suspected that the antiangiogenesis agent bevacizumab (Avastin, Genentech) was used in Kennedy's treatment.  The drug was approved by the US Food and Drug Administration in 2009 as a second-line therapy for glioblastoma and is frequently used off-label as an initial treatment.

Bevacizumab's additional benefit, however, has been debated. In 2014, data presented at the American Society of Clinical Oncology annual meeting from two pivotal trials — the Avastin in Glioblastoma (Adagio) trial and the Radiation Therapy Oncology Group (RTOG) 0825 trial — showed a similar prolongation of progression-free survival, from 6 months to 10 months, but no significant effect on overall survival.

Hopes had been high for immunotherapy in glioblastoma, but a recent phase 3 trial with nivolumab (Opdivo, Bristol-Myers Squibb) showed no survival benefit.

CAR T-cell therapy — in which an individual's immune cells are reengineered to recognize cancer-specific proteins — has had mixed results. One patient with recurrent multifocal glioblastoma had a complete response, with huge improvements in quality of life, and a 7.5-month remission after CAR T therapy, as reported by Medscape Medical News in December 2016. The patient went on to develop new tumors.

Another more recent trial in 10 patients at the University of Pennsylvania in Philadelphia found no clinical benefit. One patient did achieve stable disease at the 18-month follow-up; 2 others had disease progression, and the final 7 lived longer than predicted, based on the number of previous treatments and the multifocal nature of the tumor recurrences.

Tributes Pour In

After McCain revealed his diagnosis, politicians and others issued tributes, with many calling the former prisoner of war an American hero.

"Senator John McCain has always been a fighter," said President Donald Trump, in a statement. "Melania and I send our thoughts and prayers to Senator McCain, Cindy, and their entire family. Get well soon."

McConnell echoed those words. McCain "has never shied from a fight and I know that he will face this challenge with the same extraordinary courage that has characterized his life," he said in a statement

Former President Barack Obama tweeted, "Cancer doesn't know what it's up against. Give it hell, John."

McCain's daughter, Megan, tweeted a lengthy statement of praise for her father. "It won't surprise you to learn that in all this, the one who is most confident and calm is my father," she said. "Cancer may afflict him in many ways, but it will not make him surrender. Nothing ever has."

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