- Results of the PANOVA-3 open-label, randomized phase 3 study show that compared with chemotherapy alone, the concomitant use of adding Tumor Treating Fields (TTFields) to gemcitabine/nab-paclitaxel improves survival in patients with unresectable, locally advanced pancreatic cancer.
- To date, no phase 3 studies have demonstrated a survival benefit in this setting, with the current standard of care extrapolated from clinical trials in patients with metastatic PANOVA-3 is the first phase 3 study to demonstrate significantly improved overall survival in this patient population.
- The findings, co-authored by Teresa Macarulla, a Medical Oncologist at the Vall d’Hebron University Hospital and Head of VHIO’s Upper Gastrointestinal and Endocrine Tumors Group, were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in the Journal of Clinical Oncology.
The phase 3 PANOVA-3 clinical trial evaluated the efficacy and safety of adding Tumor Treating Fields (TTFields) to standard-of-care chemotherapy with gemcitabine and nab-paclitaxel versus chemotherapy alone as front-line treatment of unresectable, locally advanced pancreatic adenocarcinoma. TTFields is a non-invasive therapy which utilizes low intensity alternating electric fields to disrupt cancer cell division and growth, delivered by a portable device.
TTFields have previously shown significant activity in vitro and in vivo in pancreatic cancer models, with enhanced efficacy when used with chemotherapy. Showing that TTFields therapy with gemcitabine with or without nab-paclitaxel was feasible, safe, and active in patients with advanced disease, results from the pilot phase 2 PANOVA trial served as the basis for PANOVA-3.
Results from this study, co-authored by Teresa Macarulla, a Medical Oncologist at the Vall d’Hebron University Hospital and Head of VHIO’s Upper Gastrointestinal and Endocrine Tumors Group, were presented at the 2025 ASCO Annual Meeting by Vincent Picozzi of the Virginia Mason Medical Center in Seattle. Findings demonstrated that compared with chemotherapy alone, the concomitant use of adding TTFields to gemcitabine plus nab-paclitaxel led to improved overall survival (OS), pain-free survival and progression-free survival (PFS) in patients with inoperable, locally advanced disease. These data published simultaneously in the Journal of Clinical Oncology*.
The first and only phase 3 trial to demonstrate a statistically significant benefits specifically in unresectable, locally advanced pancreatic cancer
Most patients with pancreatic adenocarcinoma present with advanced disease at diagnosis, which remains difficult to treat. With 5-year survival rates between 8% and 13%, the prognosis for these patients is poor.
“Up until now, no phase 3 studies have demonstrated a survival benefit in patients with inoperable, locally advanced pancreatic adenocarcinoma. Approved treatment approaches have been extrapolated from clinical studies in the metastatic setting. PANOVA-3 is the first to evaluate a new treatment strategy specifically in patients with locally advanced disease,” said Teresa Macarulla.
A total of 571 patients were enrolled in PANOVA-3 who were randomly assigned 1:1 to TTFields therapy plus gemcitabine/nab-paclitaxel or chemotherapy alone. The median OS was 16.2 months with TTFields plus gemcitabine and nab-paclitaxel versus 14.2 months with chemotherapy alone. Pain-free survival was significantly prolonged with TTFields plus the chemotherapy combination (median 15.2 vs. 9.1 months), as was distant PFS (median 13.9 months vs. 11.5 months).
76.3% of patients who received TTFields therapy experienced device-related skin adverse events (AEs). Most of these device-related skin AEs were mild to moderate, grade 1 or 2, and no new safety signals were observed.
“This pivotal study is the only phase 3 trial specifically in locally advanced disease to show clinically meaningful benefit, establishing TTFields with gemcitabine/nab-paclitaxel as an effective new treatment strategy for this patient population. Having demonstrated improved overall survival, pain-free survival, and distant progression-free survival, adding TTFields therapy to standard-of-care chemotherapy represents a potentially transformative advance in the management of these patients,” concluded Macarulla.
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References
2025 ASCO Annual Meeting, May 30 – June 3, Chicago, IL
Corresponding session details:
Oral Abstract Session
Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary
Date: May 31, 2025
Time: 15:00h CT (22:00h CEST)
Room: Hall D1
LBA4005 PANOVA-3: Phase 3 study of tumor treating fields (TTFields) with gemcitabine and nab-paclitaxel for locally advanced pancreatic ductal adenocarcinoma (LA-PAC). Vincent J. Picozzi, Hani M. Babiker, Sreenivasa R. Chandana, Bohuslav Melichar, Anup Kasi, Gang Jin, Javier Gallego, Andrea J. Bullock, Hao Chunyi, Lucjan Wyrwicz, Arsen Osipov, Christelle De La Fouchardiere, Tomislav Dragovich, Woo Jin Lee, Kynan Feeney, Philip Philip, Makoto Ueno, Eric Van Cutsem, Thomas Seufferlein, Teresa Macarulla, PANOVA-3 Study Investigators
*Hani Babiker,* Vincent Picozzi,* Sreenivasa Chandana, Bohuslav Melichar, Anup Kasi, Jin Gang, Javier Gallego, Andrea Bullock, Hao Chunyi, Lucjan Wyrwicz, Erika Hitre, Arsen Osipov, Christelle de la Fouchardiere, Inmaculada Ales, Tomislav Dragovich, Woojin Lee, Kynan Feeney, Philip Philip, Makoto Ueno,Eric Van Cutsem, Thomas Seufferlein, Teresa Macarulla on behalf of the PANOVA-3 study investigators. Tumor Treating Fields with gemcitabine and nab-paclitaxel for locally advanced pancreatic adenocarcinoma: randomized, open-label, pivotal phase 3 PANOVA-3 study. JCO may 31st. DOI: 10.1200/JCO-25-00746
