TY - JOUR
T1 - Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma
T2 - Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study
AU - Babiker, Hani M
AU - Picozzi, Vincent
AU - Chandana, Sreenivasa R
AU - Melichar, Bohuslav
AU - Kasi, Anup
AU - Gang, Jin
AU - Gallego, Javier
AU - Bullock, Andrea
AU - Chunyi, Hao
AU - Wyrwicz, Lucjan
AU - Hitre, Erika
AU - Osipov, Arsen
AU - de la Fouchardiere, Christelle
AU - Ales, Inmaculada
AU - Dragovich, Tomislav
AU - Lee, Woojin
AU - Feeney, Kynan
AU - Philip, Philip
AU - Ueno, Makoto
AU - Van Cutsem, Eric
AU - Seufferlein, Thomas
AU - Macarulla, Teresa
AU - PANOVA-3 Study Investigators
A2 - Greil, Richard
N1 - nicht zu werten, Greil study group member
(Appendix: Salzburg Uniklinik fur Innere Medizin)
PY - 2025/7/20
Y1 - 2025/7/20
N2 - PURPOSE: Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC).METHODS: In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc.RESULTS: OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE.CONCLUSION: This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.
AB - PURPOSE: Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC).METHODS: In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc.RESULTS: OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE.CONCLUSION: This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.
KW - Humans
KW - Gemcitabine
KW - Deoxycytidine/analogs & derivatives
KW - Paclitaxel/administration & dosage
KW - Pancreatic Neoplasms/pathology
KW - Albumins/administration & dosage
KW - Male
KW - Female
KW - Middle Aged
KW - Aged
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Adenocarcinoma/therapy
KW - Adult
KW - Progression-Free Survival
KW - Aged, 80 and over
U2 - 10.1200/JCO-25-00746
DO - 10.1200/JCO-25-00746
M3 - Original Article
C2 - 40448572
SN - 0732-183X
VL - 43
SP - 2350
EP - 2360
JO - JOURNAL OF CLINICAL ONCOLOGY
JF - JOURNAL OF CLINICAL ONCOLOGY
IS - 21
ER -