Tumor Treating Fields and Quality of Life Among Patients With Locally Advanced Pancreatic Adenocarcinoma: A Secondary Analysis of a Randomized Clinical Trial

Importance The PANOVA-3 trial demonstrated the survival benefit and tolerability of Tumor Treating Fields (TTFields) therapy concomitant with gemcitabine and nab-paclitaxel, but understanding the impact of TTFields therapy on quality of life (QoL) and pain is important for clinical decision-making. Objective To analyze the impact of TTFields therapy concomitant with gemcitabine and nab-paclitaxel on QoL and pain outcomes using prospective data from PANOVA-3. Design, Setting, and Participants This is a prespecified secondary analysis of PANOVA-3, which was a global, open-label, multicenter, phase 3 randomized clinical trial in adult patients with previously untreated locally advanced unresectable pancreatic adenocarcinoma (LA-PAC). A total of 571 patients were randomized between May 1, 2018, and March 31, 2023, with follow-up completed October 31, 2024. Data analysis was performed from November 2024 to May 2025. Intervention Patients were randomized 1:1 to receive either TTFields therapy (150 kHz) with gemcitabine and nab-paclitaxel or gemcitabine and nab-paclitaxel alone. Nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1000 mg/m 2 ) were administered intravenously on days 1, 8, and 15 of 28-day cycles. Duration of follow-up was 18 months. Main Outcomes and Measures QoL was measured using the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire and the 26-item pancreatic cancer module. End points were mean changes from baseline QoL scores, deterioration-free survival of QoL, and time to opioid use. An analysis of pain medication use was performed post hoc. Results At baseline, 562 patients (median [IQR] age, 67 [31-90] years; 295 [52.5%] female), including 279 of 285 patients in the TTFields plus gemcitabine and nab-paclitaxel arm and 283 of 286 patients in the gemcitabine and nab-paclitaxel arm, completed the EORTC QLQ-C30 questionnaire. Global health status was stable during the 26-month follow-up in both study arms. Digestive symptoms, pain, and pancreatic pain were improved from 2 months after treatment initiation throughout treatment and follow-up in the TTFields plus gemcitabine and nab-paclitaxel arm. TTFields plus gemcitabine and nab-paclitaxel was associated with longer deterioration-free survival for global health status than gemcitabine and nab-paclitaxel alone (median [IQR], 7.1 [3.5-14.8] vs 5.7 [2.3-11.5] months; hazard ratio [HR], 0.77; 95% CI, 0.61-0.97; P = .02). Longer deterioration-free survival was also observed for most items on the digestive symptoms scales (indigestion and altered bowel habit were similar between the 2 arms). Median (IQR) deterioration-free survival was significantly longer with TTFields plus gemcitabine and nab-paclitaxel for pain (10.1 [4.0-20.9] vs 7.4 [3.5-14.5] months; HR, 0.70; 95% CI, 0.54-0.89; P = .003) and pancreatic pain (14.7 [6.2-46.2] vs 10.2 [5.6-18.2] months; HR, 0.69; 95% CI, 0.52-0.90; P = .006) as was median time to opioid use in the modified intention-to-treat population (9.3 [3.9-18.6] vs 6.7 [1.1-16.3] months; HR, 0.72; 95% CI, 0.55-0.93; P = .01). Conclusions and Relevance This secondary analysis of a randomized clinical trial found that TTFields therapy with gemcitabine and nab-paclitaxel improved QoL and provided clinically meaningful benefits in pain outcomes compared with gemcitabine and nab-paclitaxel alone. This study’s results suggest that TTFields therapy with gemicitabine and nab-paclitaxel is practice-changing for patients with unresectable LA-PAC. Trial Registration ClinicalTrials.gov Identifier: NCT03377491