Dr Philip on the Mechanism of Action of TTFields in Locally Advanced Pancreatic Cancer

“This is a gentle way of trying to control the cancer and the environment it sits in.”

Philip A. Philip, MD, the director of Gastrointestinal Oncology, co-director of the Pancreatic Cancer Center, and medical director of Research and Clinical Care Integration at the Henry Ford Cancer Institute, discussed how tumor treating fields (TTFields) work and their role in locally advanced pancreatic cancer.

TTFields are alternating electrical currents that pass through the tumor area and have been in use for a long time, Philip explained. Their use began in brain tumors and later extended to the management of rare thoracic cancers, including mesothelioma, where they were tested and approved. More recently, TTFields have become interesting in pancreatic cancer because, like radiation, they are noninvasive: they involve no surgery and are administered outside the body, with the patient wearing the electric fields around the abdomen over the area where the tumor is seen, he said.

At their core, TTFields disrupt cancer cells and their proliferation, but in Philip’s opinion, they go beyond that by also interfering with the tumor microenvironment (TME). Overall, he said, TTFields shift the biology of the tumor toward a more favorable state that helps control its growth, and by changing the TME, they can also help patients symptomatically, according to Philip.

In February 2026, the FDA approved Optune Pax, a first-of-its-kind, portable, noninvasive device that delivers TTFields to the abdomen, for concomitant use with gemcitabine and nab-paclitaxel (Abraxane) for the treatment of adult patients with locally advanced pancreatic cancer. The approval was supported by data from the phase 3 PANOVA-3 trial (NCT03377491), which randomly assigned 571 patients 1:1 to receive Optune Pax plus gemcitabine and nab-paclitaxel or gemcitabine plus nab-paclitaxel alone.

In the intent-to-treat population, the addition of Optune Pax produced a statistically significant improvement in median overall survival (OS), at 16.2 months (95% CI, 15.0-18.0) vs 14.2 months (95% CI, 12.8-15.4) with chemotherapy alone (hazard ratio [HR], 0.82; 95% CI, 0.68-0.99; P = .039). In the modified per-protocol population, the median OS was 18.3 months (95% CI, 16.1-20.0) vs 15.1 months (95% CI, 13.4-17.0; HR, 0.77; 95% CI, 0.62-0.97; P = .023).

The Optune Pax regimen also extended the median time to pain progression to 15.2 months (95% CI, 10.3-22.8) vs 9.1 months (95% CI, 7.4-12.7) with chemotherapy alone and prolonged quality-of-life deterioration–free survival, without increasing systemic toxicity. The most common device-related adverse events were skin reactions beneath the arrays, which were mostly grade 1 or 2.