An entirely new treatment modality is turning heads in the world of cancer treatment.
Tumor-Treating Fields (TTFields) use low-intensity electric fields to disrupt the cell division process, making it harder for cancerous cells to multiply.Read More
“TTFields only have non-overlapping toxicity with conventional anti-cancer treatments, but they also may enhance the efficacy of conventional treatment,” says Dr. Shi, whose research has focused on optimizing TTFields treatment for patients with glioblastoma (GBM). “I anticipate the utilization of TTFields will increase and may be as routinely used as other anti-cancer treatments.”
TTFields is still a relatively new treatment option. It was developed by Novocure and is called Optune. The FDA first approved it to treat glioblastoma in 2011, and then approved it in 2019 to treat mesothelioma.
A large phase 3 randomized trial has proven the use of TTFields can markedly improve the overall survival of patients with newly diagnosed GBM, Dr. Shi says, adding that the National Comprehensive Cancer Network has given TTFields its level 1 recommendation (strongest endorsement based on scientific evidence) for newly diagnosed GBM patients. “TTFields clearly is a new weapon for oncologists,” says Dr. Shi, adding that the therapy has more than doubled the five-year survival rate for newly- diagnosed GBM patients.
TTFields have been studied for use in the treatment of several other cancers, including those of the pancreas, ovaries and the lungs. The therapy is usually paired with another cancer treatment to take on the disease on multiple fronts.
“For the near future, finding out which other treatments it synergizes with best is really the focus,” says Dr. Debashish Bose, a leading expert in complex oncology and GI surgeries at Mercy Medical Center in Baltimore. “After being tested in patients with late- or end-stage disease, research can move to seeing how adding TTFields to standard treatments in earlier stages might improve outcomes.”
Most recently, NovoCure announced an encouraging result in a trial involving the use of TTFields and immune checkpoint inhibitors and TTFields coupled with the chemotherapy drug docetaxel. Yoram Palti, professor emeritus of physiology and biophysics at Technion—Israel Institute of Technology, founded Novocure to develop his pioneering research into TTFields.
In the trial, researchers are comparing how patients fare with a treatment that includes TTFields plus immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone in the treatment of stage 4 non-small cell lung cancer following failure with platinum-containing chemotherapy.
Novocure recently announced that an independent monitoring committee reviewed Novocure’s initial results and found the safety and effectiveness of TTFields so encouraging that the committee said the timeline for the study could be accelerated and that Novocure wouldn’t need to enroll as many patients as previously planned.
The news is especially encouraging as doctors continue to search for more effective options for hard-to-treat cancers. So far, TTFields appear to be best suited as partners to other proven therapies, rather than solo treatments.
Dr. Bose, who is not involved in the Novocure trial, says, “TTFields may provide a modest boost to the activity of chemotherapies, and possibly targeted agents and immunotherapies. Current data suggests that it may not accomplish much when used alone.”
How TTFields Work
When a cell is ready to divide, the genetic material contained in its nucleus lines up in the center of the cell. Highly charged proteins within the cell form chains that pull apart copies of the genetic material, allowing the cell to divide into two identical copies.
TTFields are electrical fields that pulse through the skin from transducers placed on the body near the site of the tumor. They create “fields of interruption” that interfere with the proteins’ ability to form chains that are crucial to cellular division. When cells can’t divide normally, they eventually die. The more cancerous cells that die, the more a tumor shrinks.
Though the results of TTFields are obvious and encouraging, researchers still have much to learn about this treatment. “I think there is additional promise in understanding the underlying mechanism of how TTFields really works against cancer and positioning TTFields with other cancer treatments or creating new therapies based on this better understanding,” says Dr. Phuoc Tran, clinical director of radiation oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Fortunately, healthy cells are at low risk from TTFields, compared to chemotherapy drugs, for example, which can’t distinguish between healthy and cancerous cells.
Dr. Bose notes that healthy cells have some protection because they divide more slowly, so they provide fewer targets for TTFields’ disruptive forces. “The specific effect on cancer cells is due to the fact that cancer cells divide at a much faster rate than normal cells,” he explains. “So, some slower cancers may not be as good targets as other faster-dividing cancers.”
Sofia Morazzo, a cancer researcher with the International Clinical Research Center at St. Anne’s University Hospital in Brno, Czech Republic, agrees that while most solid tumors could theoretically benefit from TTFields, there may be exceptions. “It is important to evaluate the effect in non-cancerous cells, particularly organs with a higher level of cell division, which might not benefit as much since, possibly, the treatment can not be applied the same way,” she says. “Also, the ease of application for certain organs, in terms of location, might be harder to accomplish, such as intestinal tumors.”
And because many healthy cells are spared in TTFields therapy, the risk of side effects is much lower. “Most of the experience shows some skin irritation as the treatment is given by applying large electrode pads and wearing them for an extended period of time,” Dr. Bose says. “Otherwise it seems pretty safe.”
Is It A Gamechanger?
There is still much to be learned about which cancers are best suited to TTFields therapy and which combinations of treatments that include TTFields will prove to be the most effective. But according to the journal Frontiers in Oncology (October 2020), there have been six completed TTFields clinical trials, while another 14 trials are ongoing at different phases, giving researchers reason to be optimistic that promising results are in store.
“There are so few real game changers, so I would not negate the potential benefit that TTFields may have on cancer treatment,” Dr. Tran says. “It has been awarded FDA approval in two exceptionally difficult to treat cancers, so that is extremely promising by itself.”