Editor’s Note: The 2025 ESMO Gastrointestinal Cancers Congress (ESMO GI), held in Barcelona from July 2–5, brought together leading experts and the latest global advances in GI oncology. Among the highlights was PANOVA-3, the world's largest and only successful Phase III trial in locally advanced pancreatic cancer (LAPAC), which reported its primary endpoint data at the 2025 ASCO Annual Meeting. At ESMO GI, Professor Teresa Macarulla, Chair of the Congress and GI/Endocrine Tumors Director at Vall d’Hebron University Hospital, presented new data as a late-breaking abstract (LBA) focusing on patient-reported outcomes and quality of life (QoL). The study received widespread attention for demonstrating that Tumor-Treating Fields (TTFields), when combined with chemotherapy, not only prolong overall survival but also significantly improve pain control and quality of life in LAPAC patients—offering substantial clinical value.Oncology Frontier invited Professor Gang Jin, principal investigator of PANOVA-3 in China and Chair of the Department of Hepatobiliary and Pancreatic Surgery at Changhai Hospital, Naval Medical University, and Professor Teresa Macarulla for a cross-regional conversation, offering an in-depth interpretation of PANOVA-3’s clinical findings and implications.
Professor Gang Jin Chair, Department of Hepatobiliary, Pancreatic and Spleen Surgery Changhai Hospital, Naval Medical University Professor and Doctoral Supervisor
Professor Teresa Macarulla Head of the GI and Endocrine Tumors Unit Department of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain
Q: At the recently concluded ESMO GI Congress, the quality of life data from PANOVA-3 was officially presented. Could you walk us through the study design and the key findings?
Professor Gang Jin: PANOVA-3 is currently the largest global, randomized, open-label, Phase III trial conducted in patients with locally advanced pancreatic cancer (LAPAC). The primary objective was to evaluate the efficacy and safety of TTFields therapy combined with gemcitabine and nab-paclitaxel (GnP) in this patient population. A total of 571 newly diagnosed adult LAPAC patients were randomized 1:1 to receive either TTFields at 150 kHz plus GnP or GnP alone. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), local PFS, objective response rate (ORR), pain-free survival, and quality of life (QoL). A post-hoc analysis also assessed distant PFS.
At ASCO 2025, the main efficacy results were released: TTFields combined with chemotherapy significantly extended OS and reduced the risk of death by nearly 20% (median OS: 16.2 vs. 14.2 months, HR=0.82, P=0.039). Importantly, the combination also markedly reduced the risk of distant metastasis (median distant PFS: 13.9 vs. 11.5 months, HR=0.74, P=0.022), which is a critical factor in improving prognosis for LAPAC.
In terms of quality of life, TTFields plus chemotherapy alleviated pain and meaningfully improved patients’ well-being. Median pain-free survival was extended by 6.1 months (15.2 vs. 9.1 months, HR=0.74, P=0.027), and time to deterioration in global health status was also prolonged (7.1 vs. 5.7 months, HR=0.77, P=0.023). The safety profile was favorable—TTFields did not exacerbate systemic toxicity associated with chemotherapy. The main TTFields-related adverse events were mild to moderate skin reactions, such as dermatitis (27.7%), rash (17.5%), and pruritus (15.0%).
At the ESMO GI Congress, more detailed QoL and pain-related outcomes were presented. TTFields plus GnP delayed both overall pain progression and pancreatic cancer-related pain progression compared to GnP alone. Median time to pain progression was 10.1 vs. 7.4 months (P=0.003), and median time to pancreatic pain progression was 14.7 vs. 10.2 months (P=0.006). Notably, the need for opioid initiation was also delayed (7.1 vs. 5.4 months, P=0.046).
Moreover, except for symptoms like dyspepsia and changes in bowel habits, most other GI symptoms deteriorated more slowly in the TTFields group. Overall quality of life was better maintained, and wearing TTFields did not worsen general symptoms like insomnia.
PANOVA-3 proves that TTFields combined with chemotherapy not only significantly improves OS in LAPAC patients, but also enhances their quality of life. Only around 6% of Phase III oncology trials achieve simultaneous gains in both OS and QoL, making PANOVA-3 a landmark achievement in LAPAC. As one of the investigators, I’m very pleased to see the study reach such a milestone.
Professor Teresa Macarulla: Locally advanced pancreatic cancer accounts for about 20%–30% of all pancreatic cancer cases and often involves significant tumor-related symptoms that severely affect patients’ daily lives. In PANOVA-3, TTFields plus chemotherapy demonstrated a statistically significant survival benefit over chemotherapy alone, and importantly, showed clear advantages in pain control and overall quality of life. These improvements speak to the therapy’s potential to ease tumor-related symptoms while maintaining a better quality of life throughout treatment.
The safety profile is also a key highlight. TTFields did not increase systemic toxicity; the only noted side effect was manageable skin irritation. Overall, the combination allowed patients to maintain a higher level of well-being for longer, while also providing survival benefits. I believe PANOVA-3 represents a major step forward in the treatment of LAPAC.
02 Oncology Frontier: This study included a dedicated analysis of pain outcomes in patients with locally advanced pancreatic cancer (LAPAC), highlighting the benefit of TTFields in pain management. From your perspective, what is the clinical significance of this improvement in pain control for both physicians and patients?
Professor Gang Jin: As we know, pain is one of the most prominent and distressing symptoms in pancreatic cancer, severely affecting both the effectiveness of antitumor therapy and patients’ quality of life. Pancreatic cancer tends to be neurotropic, often invading the celiac nerve plexus behind the pancreas and causing severe pain. Moreover, multiple types of pain—somatic, visceral, and neuropathic—frequently coexist, making pain management in pancreatic cancer particularly challenging. Therefore, delaying the progression of pain and prolonging pain-free survival is not only central to improving patient experience but also a key indicator of effective cancer control.
TTFields combined with GnP offers meaningful clinical value by improving pain management and quality of life. First, it significantly prolongs the time without pain worsening, sparing patients from prolonged suffering and helping them maintain a more comfortable physical condition. Second, it delays the need for opioid use, reducing the risk of opioid dependency and minimizing the common side effects of strong analgesics such as constipation, drowsiness, nausea, and cognitive impairment. This helps patients better manage cancer-related pain and preserve daily functioning.
Third, effective pain control combined with fewer drug-related side effects improves the overall treatment experience, reduces the psychological and physical burden of disease, and boosts patients’ motivation and confidence, thereby enhancing adherence to treatment. Finally, higher treatment adherence increases the likelihood that patients will complete a full and adequate course of antitumor therapy, ultimately supporting longer survival.
Professor Teresa Macarulla: Absolutely. I believe pain control is a key highlight of the PANOVA-3 study. Most LAPAC patients experience significant pain that drastically diminishes their quality of life and necessitates the use of strong opioids like morphine. From a clinical standpoint, anything that can alleviate pain or prolong pain-free periods is a substantial benefit. The PANOVA-3 data presented at ESMO GI showed that TTFields reduced the need for strong painkillers and delayed pain onset—this is a very encouraging signal for both physicians and patients.
Professor Gang Jin: In summary, TTFields combined with chemotherapy offers a significant advantage in delaying the progression of pain in pancreatic cancer. This not only improves patients’ lived experience and preserves their dignity, but also equips clinicians with a powerful tool for managing quality of life. By enhancing treatment adherence, it indirectly supports better antitumor outcomes and enables the dual benefit of longer survival and better quality of life—a highly valuable addition to comprehensive pancreatic cancer care.
03 Oncology Frontier: Based on your experience with the PANOVA-3 trial, could you share a particularly memorable patient case?
Professor Gang Jin: Our center enrolled 14 patients with locally advanced pancreatic cancer in the PANOVA-3 trial—7 received TTFields plus GnP, while the other 7 received GnP alone. Preliminary analysis showed that the median overall survival (mOS) in the TTFields group was 15.1 months, compared to 11.4 months in the control group. These figures were slightly lower than the global median, likely due to poorer baseline conditions among our patients: around 45% had baseline CA19-9 levels exceeding 1200 U/mL, and all had lymph node metastasis.
Among them, two cases stood out. One patient with pancreatic head cancer achieved a partial response (PR) at the first evaluation, with tumor shrinkage exceeding 50% over time. This patient had a progression-free survival (PFS) of over one year and an overall survival of 30 months. Another patient had a 6 cm tumor in the body and tail of the pancreas and baseline CA19-9 >1200 U/mL. After six months of treatment, this patient also achieved PR with a nearly 30% tumor reduction, and lived for 16 months.
Notably, both patients had excellent adherence to TTFields therapy, with daily usage rates averaging around 80%, suggesting that consistent use of the device may play an important role in achieving better outcomes.
04 Oncology Frontier: Based on the findings of PANOVA-3, what are your expectations for future clinical research or practice with TTFields?
Professor Gang Jin: I have three main expectations for the next stage of development:
1. Optimization and expansion of combination therapies: At ESMO GI, we were pleased to see basic research data exploring TTFields in combination with FOLFIRINOX. The results suggest that TTFields may further suppress tumor growth when added to FOLFIRINOX, potentially by inducing DNA damage and downregulating key DNA repair pathways. As GnP remains the most widely used chemotherapy regimen for LAPAC, and FOLFIRINOX/NALIRIFOX are also viable options, it would be valuable to explore TTFields in combination with these alternatives. The focus should be on evaluating whether these intensified regimens, when paired with TTFields—which lacks systemic toxicity—can boost survival benefits without compounding hematologic, neurologic, or gastrointestinal side effects. Additionally, future studies could investigate the potential of adding radiotherapy or immunotherapy (e.g., checkpoint inhibitors) to the TTFields-chemotherapy backbone, seeking synergistic combinations to further improve outcomes.
2. Identifying patients most likely to benefit: PANOVA-3 demonstrated the potential of TTFields plus GnP in LAPAC. Moving forward, identifying predictive biomarkers or clinical characteristics that correlate with TTFields response will be essential. This would enable more precise patient selection, optimize treatment decision-making, and improve the efficiency of healthcare resources while maximizing quality of life.
3. Accelerating approval and real-world validation: We hope that TTFields will soon be approved for LAPAC based on solid clinical evidence, making it accessible in broader real-world settings. Future real-world studies should include quality of life as a core endpoint and investigate how to further ease treatment burdens through optimized regimens, enhanced patient education, and support systems. Ultimately, we aim to ensure patients not only live longer but live better and with dignity.
Professor Teresa Macarulla: The most impactful contribution of PANOVA-3 is that it’s the first Phase III study in LAPAC to achieve a positive OS result, and it has the potential to change the current standard of care. At present, chemotherapy remains the mainstay for these patients. In the future, we could consider incorporating TTFields to enhance survival and quality of life. Next, we plan to launch the single-arm Phase II PANOVA-4 study to explore the combination of TTFields, chemotherapy, and immunotherapy in metastatic pancreatic cancer. One of our goals is to determine whether TTFields can modify the pancreatic tumor microenvironment to make it more responsive to immunotherapy. We hope this research will provide valuable answers.
