Tumor Treating Fields Boost Pancreatic Cancer Survival

The addition of low-intensity electric tumor treating fields (TTFields) therapy to first-line standard chemotherapy was associated with significantly improved overall survival in a phase 3 trial for patients with unresectable, locally advanced, pancreatic adenocarcinoma (LA-PAC). 

The PANOVA-3 trial “establishes tumor treating fields with gemcitabine/nab-paclitaxel as a potential new standard treatment paradigm for unresectable, locally advanced pancreatic cancer,” reported Vincent J. Picozzi, MD, first author of the new research, at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting. 

The new study, which was simultaneously published in the Journal of Clinical Oncology, is the first phase 3 trial to show an overall survival (OS) benefit for any treatment added to standard chemotherapy in this patient population, where the current 5-year OS rate is less than 8%, said Picozzi in his presentation.

TTFields is a non-invasive therapy that delivers electricity to the tumor site via a wearable device and transducer arrays placed on the skin. The electric fields “disrupt processes critical for cancer cell division and may do a variety of other things, such as trigger an enhanced anti-tumor response,” he explained. The therapy has already been approved in the United States and Europe for use in various cancers, including glioblastomas, metastatic pleural mesothelioma, and metastatic non-small cell lung cancer (NSCLC).

Study Methods

The open-label study, conducted across 20 countries and 196 sites, included 571 patients with unresectable, locally advanced, biopsy-confirmed, and previously untreated pancreatic adenocarcinoma. Participants had a life expectancy of at least 3 months and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.

The patients (median age 67 years, 47.6% male) were randomly assigned to receive only gemcitabine 1000 mg/m² and nab-paclitaxel 125 mg/m² by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle (n = 286), or the same chemotherapy plus TTFields (n = 285). Patients wore the devices about 15 hours per day for about 28 weeks on average.

Notably, almost 30% of the patients were non-White, almost 4% were ECOG PS 2, “and perhaps most importantly, almost 30% had CA 19-9 levels greater than 1000, suggesting a high incidence of occult, unrecognized metastatic disease,” said Picozzi, a hematologist-oncologist and director of the Pancreaticobiliary Program at Virginia Mason Medical Center, Seattle, Washington.

Follow-up visits were every 4 weeks, with chest, abdomen, and brain CT or MRI performed every 8 weeks to assess disease progression.

Study Results

After a median follow-up of about 13 months, the primary endpoint of OS was statistically improved in the TTFields arm compared with controls (16.2 vs 14.2 months, hazard ratio [HR] 0.82, P = .039), and the 1-year survival rate was similarly better (68.1% vs 60.2%; P = .029).

There was no significant difference between groups in median progression-free survival (PFS), at 10.6 vs 9.3 months, respectively. However, the 1-year PFS rate was higher in the TTFields arm (43.9% vs 34.1%, P = .026).

“Perhaps somewhat surprisingly,” a post-hoc analysis showed a statistically significant benefit to TTFields in distant PFS, Picozzi said.

Importantly, TTFields showed benefit in quality of life.

“In pain-free survival, another secondary endpoint — which really is freedom from progression of pain over time — we see a very distinct difference” (median 15.2 vs 9.1 months, 1-year pain-free survival rate 54.1% vs 45.1%), he reported.

“Pain is a common and debilitating morbidity in patients with advanced pancreatic adenocarcinoma and a predictor of survival. Thus, by mitigating cancer pain, TTFields may preserve the quality of life of patients with LA-PAC, further supporting TTFields’ utility as first-line treatment of this disease,” the authors write in the paper.

Patients also performed quality-of-life analyses using the EORTC QLQ-C30 questionnaire, along with the pancreatic cancer–specific PAN26 addendum, “and using these tools, there was an improvement in deterioration of global health status, pain, and digestive problems,” said Picozzi.

Most serious adverse events (SAEs), occurring in 53.6% of the TTFields arm and 48% of controls, were related to chemotherapy or the underlying disease, and were not device-related, the authors wrote. 

The most common SAEs, which were relatively balanced between arms, were sepsis (6.9% TTFields vs 9.5% controls), cholangitis (5.8% vs 3.7%), bile duct obstruction (5.5% vs 3.3%), and pneumonia (5.1% vs 3.3%), which is a toxicity profile expected for gemcitabine/nab-paclitaxel, Picozzi said.

Most device-related AEs were mild-to-moderate skin reactions, consistent with previous trials of TTFields, and could be managed with topical steroids and calcineurin cream.

In total, 23 patients (8.4%) had device-related AEs leading to TTFields discontinuation, while discontinuation of chemotherapy due to chemotherapy-related AEs occurred in 17.2% in the TTFields group and 15.8% of controls.

Pros and Cons of the Device 

Study discussant Brian M. Wolpin, MD, a medical oncologist and director of the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, Boston, Massachusetts, said, “Assuming appropriate regulatory approvals, I think the combination of the survival increase and quality-of-life benefits suggests this could be an approach that we could use in patients with locally advanced pancreatic cancer.” 

But “there are some lifestyle constraints of wearing the device 18 hours a day continuously for months,” he noted. 

Wolpin’s comments also raised the question of whether TTFields could be combined with other first-line choices for LA-PAC, and pointed out that some oncologists treat locally advanced disease with chemotherapy other than gemcitabine/nab-paclitaxel.

“Many of the newer trials have now started to use multi-agent chemotherapy, many different chemotherapy programs, and different lengths of chemotherapy…Some of these trials have used radiation, some have not,” he said.

Indeed, the addition of radiation to first-line chemotherapy for LA-PAC is “very, very routine” in the United States, Michael Chuong, MD, told Medscape Medical News.

Nevertheless, Chuong, a professor of radiation oncology at Florida International University in Miami and medical director of radiation oncology at Miami Cancer Institute, called PANOVA-3’s results exciting.

“The use of chemotherapy, plus any other non-chemo treatment, has never before shown a survival difference,” he said. “For example, randomized trials of chemotherapy, plus or minus definitive radiation therapy, showed only differences in local control. I would say [this trial] definitely is going to lead to this becoming a standard-of-care option now. Whether all patients with locally advanced pancreatic cancer should be getting this remains to be seen.”

He said the trial’s ad hoc finding of statistically significant benefit for TTFields in distant PFS — but not local PFS — suggests that TTFields may be most effective at delaying metastasis.

“If it’s delaying onset of liver and peritoneal disease, which almost every one of these patients will ultimately develop, that’s huge,” he said, adding that the trial’s high number of participants with CA 19-9 levels greater than 1000 suggested a certain amount of metastatic disease in the cohort.

Other TTFields Research Is Ongoing 

Chuong is conducting a single-arm, phase 2 study in the same type of population. In his study, TTFields is being combined with stereotactic ablative body radiation (SABR) in the first-line setting, and he has hypothesized that this will delay metastasis.

“From a mechanistic standpoint, this is a treatment that’s applied to the entirety of the abdomen. These low electrical fields are delivered to the peritoneum, into the liver, and that’s where the predominant site of distant metastatic disease is in these patients.”

The study was funded by Novocure GmbH.

Picozzi disclosed stock and other ownership interests in Amgen, Cigna, Iovance Biotherapeutics, Johnson & Johnson, Lilly, McKesson, and Thermo Fisher; a scientific consulting or advisory role with Revolution Medicines, TriSalus Life Sciences; and research funding from AbbVie, Amal Therapeutics, Astellas Pharma, FibroGen, Ipsen, and NovoCureBrian. 

Wolpin disclosed a consulting or advisory role with Agenus, BeiGene, EcoR1 Capital, Harbinger Health, Ipsen, Mirati Therapeutics, Revolution Medicines, Tango Therapeutics, and Third Rock Ventures; and research funding from Amgen (Inst), AstraZeneca (Inst), Harbinger Health (Inst), Lilly (Inst), Novartis (Inst), and Revolution Medicines (Inst). 

Chuong disclosed funding from Novocure, Viewray, and Stratpharma.

Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.