TTFields Combo Shows Meaningful Benefits in Pancreatic Adenocarcinoma

"The PANOVA-3 trial may have implications beyond LA-PAC, because it further supports the potential of concomitant use of TTFields therapy with the existing standard of care in solid tumors across a range of therapeutic settings," according to the study authors.

Combining tumor treating fields (TTFields) with gemcitabine and nab-paclitaxel (Abraxane) conferred significant overall survival (OS), pain-free survival, and distant progression-free survival (PFS) benefits among patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC), according to findings from the phase 3 PANOVA-3 trial (NCT03377491) published in Journal of Clinical Oncology.¹

The TTFields combination produced a median OS of 16.2 months (95% CI, 15.0-18.0) vs 14.2 months (95% CI, 12.8-15.4) with gemcitabine/nab-paclitaxel alone (HR, 0.82; 95% CI, 0.68-0.99; P = .039). At 1 year, the OS rates were 68.1% (95% CI, 62.0%-73.5%) vs 60.2% (95% CI, 54.2%-65.7%) in each respective arm (P = .029).

The median PFS was 10.6 months (95% CI, 9.2-12.2) in the TTFields arm vs 9.3 months (95% CI, 7.6-11.1) in the comparator arm, demonstrating no significant difference in outcomes (HR, 0.85; 95% CI, 0.68-1.05; P = .137). The respective 1-year rates were 43.9% (95% CI, 36.9%-50.6%) vs 34.1% (95% CI, 27.1%-41.2%), which crossed the threshold for significance (P = .026). Additionally, the median pain-free survival was 15.2 months (95% CI, 10.3-22.8) vs 9.1 months (95% CI, 7.4-12.7) in each arm, reflecting a significant improvement with the addition of TTFields (HR, 0.74; 95% CI, 0.56-0.97; P = .027).

Data showed an objective response rate (ORR) of 36.1% (95% CI, 30.0%-42.4%) with the TTFields regimen and 30.0% (95% CI, 24.3%-36.2%) with gemcitabine/nab-paclitaxel alone (P = .094). The resectability rate was 7.0% (95% CI, 4.3%-10.6%) and 10.1% (95% CI, 6.9%-14.2%), respectively. Additionally, the median distant PFS was 13.9 months (95% CI, 12.2-16.8) in the experimental arm vs 11.5 months (95% CI, 10.4-12.9) in the comparator arm (HR, 0.74; 95% CI, 0.57-0.96; P = .022).

“In conclusion, PANOVA-3, the only phase 3 trial specifically in unresectable LA-PAC to show a significant OS benefit, establishes that TTFields with gemcitabine/nab-paclitaxel is an effective treatment [for] unresectable LA-PAC. With clinically meaningful improvements in OS, pain-free survival, and distant PFS and no exacerbation of systemic toxicity, TTFields therapy offers a potential treatment advance in the management of LA-PAC,” lead study author Hani M. Babiker, MD, from the Departments of Hematology and Medical Oncology at Mayo Clinic Comprehensive Cancer Center, wrote in the publication with coauthors.¹ “The PANOVA-3 trial may have implications beyond LA-PAC, because it further supports the potential of concomitant use of TTFields therapy with the existing standard of care in solid tumors across a range of therapeutic settings.”

In the international, open-label, phase 3 PANOVA-3 trial, 571 patients were randomly assigned to receive TTFields plus gemcitabine/nab-paclitaxel (n = 285) or chemotherapy alone (n = 286). Investigators administered treatment with TTFields at 150 kHz via the NovoTTF-200T System. Additionally, patients received nab-paclitaxel at 125 mg/m² intravenously once per day plus gemcitabine at 1000 mg/m² intravenously once daily on days 1, 8, and 15 of each 28-day cycle.

The trial’s primary end point was OS. Secondary end points included PFS, local PFS, the 1-year survival rate, pain-free survival, puncture-free survival, ORR, the resectability rate, and safety.

Patients 18 years and older with unresectable, previously untreated LA-PAC, a minimum life expectancy of 3 months, and an ECOG performance status of 0 to 2 were eligible for enrollment on the trial. Those with implantable electronic medical devices like pacemakers were among the patients who were ineligible for study entry.

The median age was 67 years (range, 31-90) in the TTFields arm and 67.5 years (range, 40-88) in the comparator arm. In each respective arm, most patients were White (70.9% vs 71.3%) and from North America (43.2% vs 43.7%); a higher proportion of patients in the TTFields arm were male (51.6% vs 43.7%). Additionally, a majority in each arm had an ECOG performance status of 1 (58.2% vs 57.0%), a body mass index of less than 25 (58.2% vs 60.8%), and tumors located on the head of the pancreas (50.2% vs 51.7%).

In the TTFields and comparator arms, 97.8% and 89.9% experienced adverse effects (AEs) of any grade, and 88.7% vs 84.2% had grade 3 or higher toxicities. In each arm, 17.2% and 15.8% discontinued chemotherapy due to AEs, and 6.2% and 5.9% experienced AEs resulting in death. Across the TTFields arm, 8.4% of patients discontinued use of the device due to toxicity.

The most common AEs of any grade in the TTFields and comparator arms, respectively, included neutropenia (62.8% vs 65.9%), fatigue (60.2% vs 54.2%), anemia (58.8% vs 57.9%), and thrombocytopenia (44.5% vs 48.7%). No patients died due to AEs associated with TTFields, although 4 died due to toxicity related to chemotherapy. One patient in the TTFields arm experienced a serious AE consisting of diarrhea, which investigators determined to be related to chemotherapy and probably related to TTFields.

“While the hope has traditionally been that more effective local therapy could increase the R0 resection rate, the PANOVA-3 trial shows us that improved [median] OS can be achieved with a local therapy, even if it does not mean more patients are rendered surgically operable,” Michael J. Pishvaian, MD, PhD, stated in a written editorial regarding the findings from the PANOVA-3 trial.² “Thus, in the not-too-distant future, there is hope that other trials that incorporate local therapy strategies as well as combinations with [TTFields] and/or better systemic therapies such as KRAS inhibitors may further improve survival and quality of life for patients with LAPC.”

Pishvaian is director of Gastrointestinal, Developmental Therapeutics, and Clinical Research Programs, and associate professor of Oncology at Johns Hopkins School of Medicine.

References

1. Babiker HM, Picozzi V, Chandana SR, et al. Tumor treating fields with gemcitabine and nab-paclitaxel for locally advanced pancreatic adenocarcinoma: randomized, open-label, pivotal phase III PANOVA-3 Study. J Clin Oncol. 2025;43(21):2350-2360. doi:10.1200/JCO-25-00746
2. Pishvaian MJ. Tumor-treating fields open the door to progress for patients with locally advanced pancreatic cancer. J Clin Oncol. 2025;43(21):2339. doi:10.1200/JCO-25-01040