n unusual cancer treatment that creates electric fields in the brain via a bathing-cap-like device can buy a few more months of life for patients with glioblastoma, the aggressive brain cancer that is essentially always fatal, physicians reported on Tuesday in JAMA, the Journal of the American Medical Association.
You’ll want to know:
The 695 patients in the study had all undergone the standard treatment for glioblastoma: surgery, radiation, and the chemotherapy temozolomide. Among the 466 who continued to receive chemotherapy only, the average time before their brain tumors returned or spread was four months. That interlude lasted on average 6.7 months, however, in the 229 patients who also received the electric-field therapy, called Optune and manufactured by Novocure. In the chemo-only group, average survival was 16 months after entering the study, compared to 20.9 months for the chemo-plus-Optune patients.
Why it matters:
Glioblastoma, which Sen. John McCain is battling, has a dismal prognosis. It strikes about 3 per 100,000 people in the U.S. every year. Some 85 percent of patients die within five years of when they’re diagnosed, 75 percent die within two years, and only half make it to 15 to 18 months. Patients and physicians are desperate for any glimmer of hope. In the last decade, there have been two dozen clinical trials of drugs for newly diagnosed glioblastoma. Zero found an improvement in survival. The last thing that was found to boost survival (by about two months) was the chemotherapy temozolimide, in 2005.
What they’re saying:
“The data are robust,” said Dr. Adilia Hormigo, director of neuro-oncology at Mount Sinai Health System in New York City, who was not involved in the study but is leading one that combines Optune with a cancer vaccine. Although the additional survival and “progression-free” period seem meager, she said, those averages conceal a fact important to patients: After two years, 43 percent of the Optune patients were alive, compared to 30 percent of the chemo-only patients. After five years, those rates were 13 percent for Optune and 5 percent for chemo-only patients.
“Is that great?” asked Dr. Roger Stupp of Northwestern University Feinberg School of Medicine, who helped design and led the JAMA study. “No, that’s the disappointing part. But it’s a 37 percent reduction in the risk of death [at two years], and the first thing we’ve had since 2004 [when the glioblastoma chemotherapy temozolomide was introduced] that improves survival.”
The Optune device, which costs about $21,000 a month, caused some skin irritation but otherwise has no serious side effects. It works by interfering with cell division; in the brain, cancer cells are almost the only ones that divide.
But keep in mind:
In the real world, the benefits of a treatment are often less than what they were in a clinical trial, and that might be the case here, too. This company-sponsored study enrolled only patients who were well enough to start chemo after surgery and radiation, said Stupp: “We could not include the absolutely worst patients.”
Even for these participants, the electric fields were not a cure. Only 16 of the original 466 patients were alive by the end of the study.
“We don’t know why it’s not curative,” said Stupp, who has received travel payments from Novocure. (Most of the study’s 29 authors are company employees or received consulting, research, or other payments from Novocure.)
One possibility is that the electric fields didn’t reach every speck of tumor. Or, because the size and shape of glioblastoma cells determine the precise electric-field frequency and intensity needed to damage them, “if a cell develops a different shape, or becomes smaller or larger, it will no longer be susceptible,” Stupp said.
In its six years on the market, Optune has had only modest uptake: 1,100 patients were using it as of a year ago, Novocure said. One reason more patients don’t use it, Hormigo said, is that it works only on a shaved head (so the electrodes make effective contact), which many patients don’t want. It also requires a portable generator, which patients (or their families) operate themselves, and has to be worn at least 18 hours a day, which can be burdensome. And some physicians who are used to prescribing drugs aren’t comfortable prescribing a device, she said.
Another concern of some oncologists is Optune’s unusual path to market. The clinical trial for glioblastoma that returned after initial treatment found that the device is no better than chemo alone, said Stupp, who led that study. Only seven of the Food and Drug Administration’s 12-member panel of outside advisers recommended approval, but the FDA nevertheless granted it in 2011. Similarly, in 2015 FDA approved it for newly diagnosed glioblastoma based on only interim results of the current clinical trial. Some physicians wondered if approval of Optune had gotten ahead of the evidence.
The greatest obstacle has been the sense that a benefit measured in months is too meager, said cancer biologist Jill Barnholtz-Sloan of Case Western Reserve University School of Medicine. “To a lot of clinicians and patients that’s just not good enough,” she said. “But you have to recognize that there are patients using it who are living past two years.”
The bottom line:
“This doesn’t mean we should declare victory” against glioblastoma, Stupp said. “But it’s one step toward improving patients’ quality of life and length of life.”