Electricity-Based Treatment Boosts Overall Survival

A technique that uses electrical fields on cancer cells has been found to increase survival when combined with standard chemotherapy for some pancreatic cancer patients.

In early December 2024, Novocure, the developer of Tumor Treating Fields (TTFields), released results of a clinical trial dubbed PANOVA-3 that showed a statistically significant improvement in overall survival. The study tested the effectiveness and safety when used along with gemcitabine and nab-paclitaxel as a first-line treatment of locally advanced pancreatic cancer.

“This trial is important because it was prospective, randomized, and actually the first phase III trial to show a real benefit to patients with locally advanced disease,” says investigator Vincent Picozzi, M.D., director of Pancreatic & Biliary Duct Cancer at Virginia Mason Medical Center  in Seattle, Washington. “I’m a clinician and a researcher and I’ve been at this a while. I can honestly say I find it exciting because this can potentially be leveraged for different stages of pancreas cancer. For a localized therapy, it may also have systemic effects. And it can be used potentially for other cancers. In pancreas cancer, I do believe this is an important move in the right direction.”

How TTFields Works

Cancerous cells are very different from healthy cells. Once they become malignant, these cells have undergone genetic, structural, and electrical changes. Normal cells have a tightly controlled sequence of events controlling cell division. But cancer cells divide uncontrollably as a result of the myriad changes they undergo. As they divide, they eventually mass together, forming a tumor. That’s where TTFields comes into play.

TTFields exploits cell division by delivering alternating electric fields to the mass of cells. That electrical current disrupts cell division and eventually causes cell death, with no effect on healthy cells. Investigations also show that TTFields disrupts cell migration, can activate the immune system to generate an antitumor response and slow down genes responsible for DNA damage repair.

This versatility is what makes TTFields a potentially important addition to treatment, says Picozzi. “There is some preclinical work showing that it (TTFields) enhances effects not only with chemotherapy, but also PARP inhibitors, immune checkpoint inhibitors, and radiation,” he adds.

The device is relatively small and can be worn in a backpack, shoulder bag, or fanny pack. The sets of electrodes, called arrays, are about the size of an over-the-counter pain relief patch. They are placed near the tumor site, with wires attached to the device. Patients must wear the device at least 70 percent of the day, Picozzi explains, adding that developers are always looking at ways to make it more user-friendly. Side effects are mild to moderate, with skin irritations being the most common. The biggest challenge for patients can be psychological acceptance of wearing a device, he notes.

About the Study

Patients in the PANOVA-3 trial were randomly assigned  to receive either TTFields therapy along with gemcitabine and nab-paclitaxel or gemcitabine and nab-paclitaxel alone. The primary outcome being looked at was overall survival. Secondary outcomes included progression-free survival and local progression-free survival, objective response rate, one-year survival rate, and quality of life, among others.

A total of 571 patients were enrolled in the study, and followed for a minimum of 18 months. Patients treated with TTFields therapy along with gemcitabine and nab-paclitaxel had a median overall survival of 16.20 months compared to 14.16 months in patients treated with gemcitabine and nab-paclitaxel alone, a statistically significant 2.0-month improvement. The survival rate benefit for patients treated with TTFields therapy increased over time with a 13 percent improvement in the overall survival rate at 12 months and a 33 percent improvement in survival rate at 24 months. TTFields therapy was well-tolerated, and safety was consistent with prior clinical studies.

Next Steps

Novocure plans to file for regulatory approval of TTFields in locally advanced pancreatic adenocarcinoma that cannot be surgically removed, based on PANOVA-3 results. The company also plans to submit full PANOVA-3 results for presentation at an upcoming medical congress.

Novocure continues to follow patients in its phase II PANOVA-4 trial, which explores the use of TTFields together with atezolizumab, gemcitabine, and nab-paclitaxel for the treatment of metastatic pancreatic cancer. The primary outcome is disease control rate. Secondary outcomes include overall survival, progression-free survival, one-year survival rate, objective response rate, progression-free survival at six months, duration of response, and toxicity. The study is designed to enroll 76 patients. PANOVA-4 has completed enrollment, with data anticipated in 2026.

While this therapy could prove to be a much-needed addition to pancreatic cancer treatment, there is more work to be done. “Broadly there are five major challenges with pancreas cancer,” says Picozzi. “First, there’s a lack of optimism. The truth is we are getting better at treatment. The second issue is that it takes a great number of people with different skills to create an optimal multidisciplinary team. I believe there aren’t 50 cancer centers in the United States that truly have the full complement of people ideal to support pancreatic cancer patients and their families.”

He also believes there needs to be a greater emphasis on supportive care. “We need to talk more about what cancer does to a patient,” he adds. “We need to deal with pain, GI complications, nutrition, and other quality of life issues.” The research in new drug classes like KRAS inhibitors and immunotherapy along with earlier detection interventions are also vital. “We need better drug treatments and we need to be able to diagnose this disease much earlier when patients are still candidates for surgery,” Picozzi states.