TTFields Plus Chemo Improves QOL, Delays Time to Pain Deterioration in Locally Advanced Pancreatic Adenocarcinoma

Tumor-treating fields (TTFields) administered in conjunction with gemcitabine plus nab-paclitaxel (Abraxane) led to an improvement in global health status (GHS) and significantly delayed time to pain deterioration and opioid use compared with gemcitabine plus nab-paclitaxel alone in patients with locally advanced pancreatic adenocarcinoma, according to data from an analysis of the phase 3 PANOVA-3 trial (NCT03377491) presented at the 2025 ESMO Gastrointestinal Cancers Congress.¹

Findings showed that based on responses to the EORTC QLQ-C30 questionnaire, patients treated with TTFields plus chemotherapy (n = 285) experienced a median time to deterioration of GHS of 7.1 months (95% CI, 5.7-9.4) compared with 5.7 months (95% CI, 4.1-7.4) for those given gemcitabine plus nab-paclitaxel alone (n = 286; HR, 0.77; 95% CI, 0.61-0.97; P = .023).

Per responses to the EORTC QLQ-C30 and PAN26 questionnaires, time to deterioration was significantly longer in the TTFields arm for most symptoms, including nausea/vomiting (P = .021), appetite loss (P = .017), constipation (P = .004), diarrhea (P = .023), bloating (P = .034), digestive symptoms (P = .005), taste loss (P = .047), flatulence (P = .015), and weight (P = .002). Statistical significance was not reached for indigestion (P = .155) and altered bowel habit (P = .085); however, both trended in favor of the TTFields regimen.

Notably, no significant difference in general symptoms was observed between the 2 arms, per responses to EORTC PAN26.

Patients treated in the TTFields arm experienced a median time to deterioration of pain of 10.1 months (95% CI, 8.0-11.6) per the EORTC QLQ-C30 questionnaire vs 7.4 months (95% CI, 5.9-9.0) in the control arm (HR, 0.70; 95% CI, 0.54-0.89; P = .003). The median time to deterioration of pancreatic pain per the EORTC PAN26 questionnaire was 14.7 months (95% CI, 12.0-16.5) vs 10.2 months (95% CI, 8.8-12.2), respectively (HR, 0.69; 95% CI, 0.52-0.90; P = .006).

“These QOL data, together with the overall survival [OS] benefit and lack of exacerbation of systemic toxicity related with chemotherapy, [position] TTFields as a new potential standard for patients with locally advanced pancreatic cancer,” lead study author Teresa Macarulla, MD, PhD, an attending physician in the Gastrointestinal Tumors Unit at Vall d’Hebron Hospital and a clinical researcher in the Gastrointestinal Tumor Program at Vall d’Hebron Oncology Institute in Barcelona, Spain, said during a presentation of the data.

PANOVA-3 Efficacy Findings

Findings from the phase 3 study shared the 2025 ASCO Annual Meeting showed that the addition of TTFields to gemcitabine and nab-paclitaxel improved overall survival (OS) vs chemotherapy alone, meeting the primary end point (HR, 0.82; 95% CI, 0.68-0.99; P = .039).² Patients in the TTFields group achieved a median OS of 16.2 months (95% CI, 15.0-18.0) compared with 14.2 months (95% CI, 12.8-15.4) for those given chemotherapy alone.

The median pain-free survival was 15.2 months (95% CI, 10.3-22.8) in the TTFields arm vs 9.1 months (95% CI, 7.4-12.7) in the control arm (HR, 0.74; 95% CI, 0.56-0.97; P = .027).

Trial Background and QOL Objectives

Investigators of PAVOVA-3 enrolled patients at least 18 years of age with previously untreated locally advanced pancreatic adenocarcinoma confirmed via biopsy.¹ Patients needed to have a life expectancy of at least 3 months and an ECOG performance status of 0 to 2. Key exclusion criteria comprised prior palliative treatment to the tumor, the presence of an implanted medical device in the torso, and known allergies to medical adhesives, hydrogel, or chemotherapies.

Patients were randomly assigned 1:1 to receive TTFields at 150 kHz for 18 hours per day in combination with 1000 mg/m² of gemcitabine and 125 mg/m² of nab-paclitaxel, with both chemotherapies given on days 1, 8, and 15 of each 28-day cycle; or the same chemotherapy regimen without TTFields. Patients were stratified by region and ECOG performance status.

Follow-up visits occurred every 4 weeks, and CT scans were given once every 8 weeks. Along with the primary end point of OS, secondary end points included progression-free survival (PFS), local PFS, overall response rate, 1-year OS rate, QOL, pain-free survival, resectability rate, and safety.

The median age was 67 years (range, 31-90) in the TTFields arm vs 67.5 years (range, 40-88) in the chemotherapy arm. Additionally, 51.6% of patients in the TTFields arm were male vs 43.7% of patients in the control arm. Most patients were White (TTFields arm, 70.9%; control arm, 71.3%), had an ECOG performance status of 1 (58.2%; 57.0%), had a body mass index below 25 kg/m² (58.2%; 60.8%), and had a target lesion site at the head of the pancreas (50.2%; 51.7%). Macarulla noted that the majority of patients had moderate CA19-9 levels between 38 and 1000 U/mL (49.1%; 53.1%) or high CA19-9 levels above 1000 U/mL (30.9%; 27.6%).

Predefined QOL end points included assessments using the EORTC QLQ C-30 and PAN26 questionnaires, along with HRQOL deterioration-free survival. Time to first opioid use was a post hoc secondary end point.

Data on Opioid Use

Findings from the post hoc analysis demonstrated that the median time to opioid use in the intention-to-treat (ITT) population was 7.1 months (95% CI, 6.2-9.3) in the TTFields arm vs 5.4 months (95% CI, 4.1-6.9) in the chemotherapy arm (HR, 0.80; 95% CI, 0.65-1.00; P = .046).

In the modified ITT population, which patients who received at least 1 full cycle of gemcitabine plus nab-paclitaxel (both arms) and at least 28 days of TTFields (for the experimental arm), TTFields plus chemotherapy (n = 198) produced a median time to opioid use of 9.3 months (95% CI, 7.1-11.0) vs 6.7 months (95% CI, 5.1-8.2) for chemotherapy alone (n = 207; HR, 0.73; 95% CI, 0.56-0.94; P = .014).

In the ITT population, 50% of patients in the TTFields arm and 49% of patients in the control arm received any opioids at least once. Within these populations, strong opioids were given to 80% and 82% of patients, respectively. Weak opioid use was recorded in 33% of patients who used opioids in the experimental arm vs 28% in the control arm.

In the modified ITT population, any opioid use was reported in 52% of patients in the TTFields arm and 53% of patients in the control arm. For those in the TTFields group, strong and weak opioids were given to 75% and 38% of patients, respectively. These respective rates were 81% and 33% in the control arm.

Disclosures: Macarulla reported serving in a consulting or advisory role for Sanofi/Aventis, Celgene, Roche, QED Therapeutics, Baxter, Incyte, Servier, Lilly, Ipsen, AstraZeneca, MSD, Eisai, Prime Oncology, Ability Pharma, Advance Medical, BioLineRX, Zymeworks, Aptitude Health, Basilea, Medscape, Novocure, Paraxel, Ellipses Pharma, Janssen, MFAR, Marketing Farmacéutico & Investigación Clínica, Amgen, Esteve, Arcus Biosciences, Boehringer Ingelheim, Taiho/Keylates, Alligator Bioscience, PEGASCY, Astellas Pharma, and Revolution Medicines; receiving institutional research funding from Celgene, Agios, ASLAN Pharmaceuticals, Bayer, Roche, Genentech, AstraZeneca, Immunomedics, Lilly, Merrimack, Millennium, Novocure, Pfizer, Pharmacyclics, AbbVie, Ability Pharma, Amc Medical Research, Amgen, Armo Biosciences, Basilea Pharmaceutica International, Beigene, Keralty Group, BiolineRx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb (BMS), Cantargia AB, Eisai, Erytech Pharma, Fibrogen, Halozyme, Incyte, Ipsen, Loxo, Medimmune, Merck Sharp & Dohme, Nelum Corp, Novartis, OncoMed, VCN Biosciences, and Zymeworks; and receiving coverage of travel, accommodations, and expenses from Merck, H3 Biomedicine, Sanofi, Celgene, Servier, Prime Oncology, Incyte, and AstraZeneca.

References

1. Macarulla T, Picozzi V, Chandana S, et al. PANOVA-3: pain and quality of life outcomes with tumor treating gields (TTFields) therapy in patients with locally advanced pancreatic adenocarcinoma (LA-PAC). Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract LBA3.
2. Picozzi V, Babiker HM, Chandana SR, et al. PANOVA-3: Phase 3 study of tumor treating fields (TTFields) with gemcitabine and nab-paclitaxel for locally advanced pancreatic ductal adenocarcinoma (LA-PAC). J Clin Oncol. 2025;43(suppl 17): LBA4005. doi:10.1200/JCO.2025.43.17_suppl.LBA4005