Lauren Dembeck, PhD

GI Oncology Now

For the first time in a phase 3 trial, a therapy has shown a statistically significant overall survival (OS) benefit in patients with unresectable locally advanced pancreatic cancer (LA-PAC). In PANOVA-3, adding tumor-treating fields (TTFields) to gemcitabine and nab-paclitaxel extended median OS and led to improvements in pain-free survival and distant progression-free survival (PFS). The findings, which were presented at the 2025 American Society of Clinical Oncology Annual Meeting, support TTFields with gemcitabine and nab-paclitaxel as a potential new standard of care for this historically hard-to-treat population.&ldquo;The current 5-year survival of adenocarcinoma of the pancreas is less than 8%. Of the third of patients who present with local advanced disease, only a small fraction are eligible for potentially curative surgery, with remaining patients being incurable and experiencing debilitating symptoms, especially pain,&rdquo; explained presenter Vincent Picozzi, MD, of Virginia Mason Medical Center.&ldquo;[T]umor-treating fields are electric fields that disrupt processes critical for cancer cell division, and may do a variety of other things, such as trigger an enhanced antitumor response,&rdquo; added Dr. Piccozi. &ldquo;Tumor-treating fields with gemcitabine and either with or without nab-paclitaxel was tested by Rivera and colleagues in an earlier-phase trial and showed that the approach using tumor-treating fields with the [aforementioned] drug combination was feasible, safe, and impressively successful.&rdquo;Dr. Piccozi reported the final data from the global, phase 3, randomized, open-label trial PANOVA-3 (ClinicalTrials.gov ID: <a href="https://clinicaltrials.gov/study/NCT03377491" target="_blank" rel="noopener">NCT03377491</a>), the largest trial in LA-PAC to date.The study enrolled adult patients with newly diagnosed unresectable LA-PAC. Patients were randomized (:1 to receive TTFields therapy (150 kHz) with gemcitabine/nab-paclitaxel or gemcitabine/nab-paclitaxel alone.The primary end point was OS. Secondary end points included PFS, local PFS, objective response rate (ORR), and pain-free survival. The investigators also conducted a post hoc analysis of distant PFS (defined as metastases beyond the pancreas and regional lymph nodes).In the intention-to-treat (ITT) population, 571 patients (median age, 67 years; range, 31-90 years; 52.4% female) were randomized&mdash;285 to the TTFields with gemcitabine/nab-paclitaxel arm and 286 to the gemcitabine/nab-paclitaxel arm. Baseline characteristics were considered generally well balanced across the treatment arms.Patients in the TTFields with gemcitabine/nab-paclitaxel arm had significantly longer median OS than those in the gemcitabine/nab-paclitaxel arm (16.2 vs 14.2 months; hazard ratio [HR], 0.82; 95% CI, 0.68-0.99; P=0.039). The 1-year median OS rate was also significantly improved with TTFields with gemcitabine/nab-paclitaxel compared with gemcitabine/nab-paclitaxel (68.1% vs 60.2%; P=0.029). Similar results were observed for the modified ITT population (median OS, 18.3 vs 15.1 months; HR, 0.77; 95% CI, 0.62-0.97; P=0.023; 1-year median OS, 75.1% vs 65.9%; P=0.022).The study found no significant difference in PFS or local PFS between the ITT treatment arms. Notably, patients in the TTFields with gemcitabine/nab-paclitaxel arm had significantly longer pain-free survival than those in the gemcitabine/nab-paclitaxel arm (median, 15.2 vs 9.1 months; HR, 0.74; 95% CI, 0.56-0.97; P=0.027). In addition, the post hoc analysis of distant PFS showed significant benefit with TTFields with gemcitabine/nab-paclitaxel compared with gemcitabine/nab-paclitaxel (median, 13.9 vs 11.5 months; HR, 0.74; 95% CI, 0.57-0.96; P=0.022). ORR was not significantly different between the TTFields with gemcitabine/nab-paclitaxel arm and the gemcitabine/nab-paclitaxel arm (36.1% vs 30.0%; P=0.094).Adverse events (AEs) occurred in 97.8% (grade &ge;3, 88.6%) of patients in the TTFields with gemcitabine/nab-paclitaxel arm and 98.9% (grade &ge;3, 84.3%) of patients in the gemcitabine/nab-paclitaxel arm. The most frequent grade 3 or higher AEs were neutropenia (47.8% and 47.6%) and anemia (21.9% and 22.3%), with TTFields with gemcitabine/nab-paclitaxel and gemcitabine/nab-paclitaxel, respectively.Among patients in the TTFields with gemcitabine/nab-paclitaxel arm, 81% had device-related AEs, which were predominantly grade 1/2 skin AEs (dermatitis, 27.7%; rash, 17.5%; and pruritus, 15.0%). Grade 3 and grade 4 device-related AEs occurred in 9.1% and 0.4% of patients, respectively.&ldquo;[The overall survival] benefit for patients is supported by significant improved quality of life and pain-free survival [with tumor-treating fields] compared to the use of gemcitabine/nab-paclitaxel alone without the use of tumor-treating fields, and the only frequently reported tumor-treating fields&rsquo; toxicity was localized skin reactions,&rdquo; concluded Dr. Piccozi. &ldquo;As such, PANOVA-3 establishes tumor-treating fields with gemcitabine/nab-paclitaxel as a potential new standard treatment paradigm for unresectable locally advanced pancreatic cancer.&rdquo;Disclosure: This research was supported by Novocure GmbH. Please see the original reference for a full list of disclosures.&nbsp;Reference:Picozzi V, et al. 2025 American Society for Clinical Oncology Annual Meeting. <a href="https://meetings.asco.org/abstracts-presentations/245458" target="_blank" rel="noopener">Abstract No. 4005</a>.

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PANOVA-3 Shows Tumor-Treating Fields Extend Survival in Locally Advanced Pancreatic Cancer

A therapy has shown a statistically significant OS benefit in patients with unresectable locally advanced pancreatic cancer.