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Variety of treatment options exist for Sen. John McCain’s glioblastoma diagnosis
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Senator John McCain (R-AZ) may choose from a variety of treatment options following the removal of a glioblastoma associated with a blood clot above his left eye.
About 12,390 new cases of glioblastomas are expected in 2017, according to the American Brain Tumor Association. The median OS associated with glioblastomas is between 12 and 18 months, with OS rates of 25% at 2 years, 15% at 3 years and about 9% at 5 years.
“There are always exceptions to rules but, realistically, glioblastomas almost always recur,” Stephanie E. Weiss, MD, associate professor in the department of radiation oncology at Fox Chase Cancer Center, told HemOnc Today. “In fact, if they do not recur we tend to think we might have been wrong about the diagnosis upfront.
“One of the things that becomes an issue is not about survival, but about PFS and the neurologic side effects patients may get from their treatments which, unfortunately, can take up a large portion of remaining life,” Weiss added.
McCain, aged 80 years, and his family are reviewing further treatment options that may include a combination of chemotherapy and radiation, according to a statement released by Mayo Clinic in Phoenix, Arizona, where McCain underwent surgery to remove the blood clot last Friday.
Treatment options
Glioblastoma — a primary brain tumor typically found above the cerebellum — is considered a grade 4 glioma, which is the most aggressive.
Prior to 2005, standard of care for patients with glioblastomas involved surgical removal of the tumor followed by radiation.
However, a 2005 study by Stupp and colleagues, published in The New England Journal of Medicine, demonstrated a median OS benefit of 2.5 months with the addition of temozolomide to radiation (median OS, 14.6 months vs. 12.1 months).
Since then, the current standard of care has been 6 weeks of radiotherapy (5 days a week) to the region at risk and areas that are likely to harbor infiltrating cells, combined with 6 weeks of daily 75 mg/m2 temozolomide.
To reduce the amount of time spent in active treatment, healthy patients may also choose hypofractionated radiotherapy combined with chemotherapy, in which radiation doses are increased and given over 3 weeks instead of 6.
Typically, following 6 weeks of radiation and chemotherapy, patients are given a 4-week break and a baseline MRI is obtained to establish a new reference point to evaluate further treatment.
Most often a patient will then receive 6 to 12 months of adjuvant 150 mg/m2 to 200 mg/m2 temozolomide for five 5 days every 28-day cycle.
McCain might also be a candidate for a tumor-treating field device called Optune (Novocure), a pad worn on a patient’s head during adjuvant therapy that delivers alternating electrical fields at an intermediate frequency of 200 MHz (1-3 V/cm) continuously to the brain, Weiss said.
“The pad generates electrical fields that disrupt the signaling at the molecular level that is required for tumor cells to divide,” Weiss said. “It disrupts only the cells that are actively in the process of dividing in the brain, which is almost exclusively tumor cells.”
Clinical trials
Alternatively, older patients with a glioblastoma are strong candidates for clinical trials.
“We’ve always known that patients who are older do not do as well,” Weiss said. “We speculate that may be because patients are not as robust and do not tolerate therapy as well. But, we are appreciating more and more about the biology of the tumor. There seems to be a prevalence of a genetic signature in older patients with glioblastomas that appears to dictate a more aggressive course.”
About half of patients diagnosed with a glioblastoma have tumors that express an amplified EGFR biomarker, Weiss said. Those with this marker should seek out clinical trials like the ongoing RTOG-3508 trial, an interventional, randomized study examining the safety and efficacy of depatuxizumab mafodotin (ABT-414, AbbVie) in combination with radiotherapy and temozolomide.
“In this trial, patients are screened and the tumor is evaluated to see if it expresses amplification of EGFR,” Weiss said. “If it does, the patient is enrolled and given a combination antibody-drug conjugate. The antibodies look for the EGFR and deliver the drug there. It basically is a homing mechanism with a payload attached.”
Weiss said it is difficult to predict how McCain will respond to treatments and whether he will be able to return to his work duties.
Senator Edward Kennedy died of glioblastoma in 2009, 15 months after it was diagnosed, and Beau Biden, son of former Vice President Joe Biden, died of glioblastoma in 2015, nearly 2 years after his diagnosis.
“The brain is unique and privileged,” Weiss said. “Whenever there is neurologic compromise, it depends on where in the brain the tumor is found. Certainly, somebody could wind up with a completely perfect performance status and be back to their old self. Some may have very severe neurologic compromise and not be able to perform their duties, and there can be any range in between.
“But, even if somebody neurologically comes back to their baseline, the therapies can have their side effects, which are variably tolerated,” Weiss said. “Some people seem to feel quite well and will say fatigue is the outstanding symptom they’re feeling. Others might have other complications that make it more difficult.”
Overall, the tumor is very aggressive, and prognosis is about 18 months, Weiss said.
“On average, older patients tend to have a worse survival,” she said. “Moving forward, consideration of clinical trials for patients who have glioblastoma is very important.” – by Chuck Gormley
Reference :
Stupp R, et al. N Engl J Med. 2005;doi:10.1056/NEJMoa043330.
For more information:
Stephanie E. Weiss, MD, can be reached at stephanie.weiss@fccc.edu.
Disclosure: Weiss reports she has no relevant financial disclosures.