Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study
Hani M. Babiker, Vincent J. Picozzi, Sreenivasa R Chandana, Bohuslav Melichar, Anup Kasi, Jin Gang, Javier Gallego, Andrea Bullock, Hao Chunyi, Lucjan Wyrwicz, Erika Hitre, Arsen Osipov, Christelle de la Fouchardière, Inmaculada Alés, Tomislav Dragovich, Woo Jin Lee, Kynan Feeney, Philip A. Philip, Makoto Ueno, Eric Van Cutsem, Thomas Seufferlein, Teresa Macarulla, on behalf of the PANOVA-3 Study Investigators, David R. Spigel, Arsen Osipov, Marc Matrana, Nicholas Blondin, Emil Lou, Rachna T. Shroff, Douglas Orr, Michael J. Anderson, Anthony F. Shields, John Hamm, Andrea Bullock, Sumana Nagireddy, Joanna Kolodney, Tomislav Dragovich, Andrew L. Coveler, Ajit Maniam, Vincent J. Picozzi, Judith D. Sears, Joseph Stilwill, Francis P. Arena, Mike Cusnir, Anna Niewiaroska, William Small, Anup Kasi, Jason Tache, Sharona Ross, Samer Shihabi, Sunil Gandhi, J. N. Reeves, Garrett Green, Trevor Feinstein, Timothy K. Huyck, Nadia Ramdin, Robert Marsh, Yixing Jiang, Hassan Hatoum, Sudhir Manda, Mark D. Kochenderfer, Henrik Illum, Donald Richards, P. Valilis, Lucas Wong, Sreenivasa R Chandana, Herbert B. Newton, Maen Abdelrahim, David Einspahr, Richard Siegel, Scott McKenney, Mohit Narang, Marc Uemura, Higinia R. Cárdenes, Kannan Thanikachalam, Joshua P. Raff, Joseph Ye, Deepti Behl, Audrey E. Kam, Paul DeRose, A. Tasneem, Warren Brenner, Jennifer De Los Santos, James Z. Wang, D C Rausch, Gaurav Trikha, Jae‐Hyun Park, Nashat Gabrail, Rex B. Mowat, Khawaja Jahangir, Robert P. Schumaker, Edward Soffen, Eric Bravin, Mukul Kumar Gupta, Hani M. Babiker, Ivan Dario Bedoya-Apraez, Tyler Y. Kang, Frédéric Lemay, Mark Vincent, Richard Létourneau
Abstract
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/m 2 and nab-paclitaxel 125 mg/m 2 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.