Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (210)
Hani M. Babiker
Division of Hematology Oncology, Mayo Clinic Florida, Jacksonville, FL
Sreenivasa R. Chandana
START Midwest, Grand Rapids, MI
Jin Gang
Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Medical University (The Second Military Medical University), Shanghai, China
Javier Gallego
Hao Chunyi
Beijing Cancer Hospital, Beijing, People's Republic of China
Inmaculada Ales
University Hospital Malaga, Malaga, Spain
Woojin Lee
Philip Philip
Henry Ford Hospital, Detroit, MI
Makoto Ueno
Thomas Seufferlein
Teresa Macarulla
Vall d’Hebrón University Hospital, Vall d’Hebrón Institute of Oncology, Barcelona
David Spigel
Arsen Osipov
Marc Matrana
Nicholas Blondin
Emil Lou
Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
Rachna Shroff
Division of Hematology and Oncology, University of Arizona College of Medicine, Tucson, AZ
Douglas Orr
Michael Anderson
Anthony Shields
John Hamm
Andrea Bullock
Harvard Medical School, Harvard University, Boston, MA
Sumana Nagireddy
Joanna Kolodney
Tomislav Dragovich
Baptist MD Anderson Cancer Center, Jacksonville, FL
Andrew Coveler
Ajit Maniam
Vincent Picozzi
Virginia Mason Medical Center, Seattle, WA
Judith Sears
Joseph Stilwill
Francis Arena
Mike Cusnir
1Mount Sinai Medical Center, Hematology Oncology, Miami Beach, United States
Anna Niewiaroska
William Small
Anup Kasi
University of Kansas Medical Center, Kansas City
Jason Tache
Sharona Ross
Samer Shihabi
Sunil Gandhi
James Reeves
Garrett Green
Trevor Feinstein
Timothy Huyck
Nadia Ramdin
Robert Marsh
Yixing Jiang
University of Maryland Marlene and Stewart Greenebaum Cancer Center, Adelphi, MD
Hassan Hatoum
Stephenson Cancer Center at The University of Oklahoma Health Sciences Center, Oklahoma City, OK
Sudhir Manda
TMC Health Cancer Center, Tucson, AZ
Mark Kochenderfer
Henrik Illum
Donald Richards
Cedars-Sinai Medical Center, West Hollywood, California, United States
Panagiotis Valilis
Lucas Wong
Baylor Scott and White Health, Temple, TX
Sreenivasa Chandana
START Midwest, Grand Rapids, MI
Herbert Newton
Maen Abdelrahim
Houston Methodist Neal Cancer Center, Houston, TX
David Einspahr
Richard Siegel
Scott McKenney
Mohit Narang
Marc Uemura
Higinia Cardenes
Kannan Thanikachalam
Roswell Park Comprehensive Cancer Center, Buffalo, NY
Joshua Raff
Joseph Ye
Deepti Behl
Mayo Clinic Rochester, Rochester, MN
Audrey Kam
Paul DeRose
Ali Tasneem
Warren Brenner
Jennifer De Los Santos
James Wang
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University
Daniel Rausch
Gaurav Trikha
Cancer Specialists of North Florida, Jacksonville, FL
David Park
University of California Irvine School of Medicine, Orange, California, United States
Nashat Gabrail
6Gabrail Cancer Center, Canton, United States
Rex Mowat
Khawaja Jahangir
Robert Schumaker
Edward Soffen
Eric Bravin
Mukul Gupta
Hani Babiker
Mayo Clinic, Jacksonville, FL
Ivan Bedoya-Apraez
Tyler Kang
Frederic Lemay
Mark Vincent
5Western University, Department of Oncology, London, Canada
Richard Letourneau
Martin Fuchs
Staedt. Klinikum Muenchen GmbH, Munich, Germany
Thomas Theodor Werner Seufferlein
Christine Doehring
Mike Haberkorn
Arndt Vogel
Karen Russwurm
Jack Chater
Marc Küng
HFR Hôpital Cantonal, Fribourg, Switzerland
Sabine Schacher
Maria Passhak
Rambam Health Care Campus-Oncology, Haifa, Israel
Ravit Geva
Department of Radiation Oncology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
Ayala Hubert
Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Salomon Stemmer
Davidoff Center, Rabin Medical Center, Tel-Aviv University, Tel-Aviv, Israel
Talia Golan
Division of Medical Oncology Sheba Medical Center Tel Aviv Medical University Tel Aviv Israel
Hélène Senellart
Department of Medical Oncology, Comprehensive Cancer Center, Institut de Cancérologie de l'Ouest, Saint-Herblain, France
Isabelle Trouilloud
Hôpital Saint-Antoine, Paris, France
Christelle de la Fouchardière
Centre Leon Berard, Lyon, France
Jean-Frederic Blan
Luis-Marie Dourthe
Florence Le Roy
Jerôme Martin-Babau
Meher Ben Abdelghani
Medical Oncology Department, ICANS, Strasbourg, France
Richard Greil
Georg Schreil
Armin Gerger
Wolfgang Eisterer
Teresa Macarulla Mercade
Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
Antonio Cubillo
Francesc Valladares Pons
Carmen Guillen Ponce
Inmaculada Ales Diaz
Hospital Regional Universitario de Malaga, Malaga, Spain
Fernando Rivera
Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
Javier Gallego Plazas
Medical Oncology Department, General Universitario de Elche Hospital, Alicante, Spain
Ricardo Yaya
Mariano Ponz Sarvise
Bruno Vincenzi
Mario Airoldi
Giovanna Bellotti
Domenico Cristiano Corsi
Medical Oncology, Isola Tiberina Hospital, Gemelli Isola, Rome, Italy
Lorenzo Antonuzzo
Azienda Ospedaliero Universitaria Careggi, Florence, Italy
Bohuslav Melichar
Petra Holeckova
Lubos Petruzelka
Rostislav Kotasek
Radim Nemecek
Eric Van Cutsem
University Hospitals Gasthuisberg, Leuven, Belgium
Jean-Luc Van Laethem
Department of Gastroenterology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
Ivan Borbath
Cliniques Universitaires Saint-Luc, Brussels, Belgium
Jun Eul Hwang
Sung Yong Oh
14Department of Oncology, Dong-A University Hospital, Busan, South Korea, Busan, Korea
Sun Jin Sym
Moon Hee Lee
Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea
Jin Young Kim
Sang Cheul Oh
Woo Jin Lee
Joon Oh Park
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Jin Won Kim
Myung Ah Lee
Hye Jin Choi
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
Seok Yun Kang
Hong Jae Chon
Lucjan Wyrwicz
Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
Rodryg Ramlau
Andrzej Mruk
Beata Freier
Ewa Kosakowska
Judit Kocsis
Bács-Kiskun Megyei Oktatókórház, Kecskemét, Hungary
Tibor Csoszi
Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
Erika Hitre
Yousuf Al-Farhat
Department of Oncology, Tolna Vármegyei Balassa János Kórház, Szekszárd, Tolna, Hungary
Ali Bassam
Chunyi Hao
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing, China
Bo Liang
Shundong Cang
Henan Provincial People's Hospital, Zhengzhou, China
Gang Jin
Changzeng Zuo
Lijie Song
Zheng Wu
Shanghai SynTheAll Pharmaceutical Co., Ltd., No. 9 Yuegong Road, Jinshan District, Shanghai 201507, China
Jie Gao
State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials
Tao Zhang
Yusheng Wang
Xinaglin Yuan
Zhihua Li
Rufu Chen
Wei Li
Xiujun Cai
Zhizhen Zhu
Yuxian Bai
Chunmei Bai
Thomas Yau
Centre of Cancer Medicine and Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
Warren Joubert
Ka Yeung Mark Wong
Gavin Marx
Kynan Feeney
St John of God Murdoch Hospital, Murdoch, WA, Australia
Marion Harris
Ana Misir
Adilson Faccio
Felipe Cruz
Instituto Brasileiro de Controle do Câncer, São Paulo, Brazil
Srergio De Azevedo
Ana Paula De Souza Victorino
Tadeu Ferreira de Paiva
Fabio André Franke
Oncosite-Oncoclínicas, Ijuí, Brazil
Katsuki Arima Tiscoski
Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
Gabriel Parolla
Flora Lilno
Mariana Bruno Siqueira
Marcos Lyra
Paulo Hoff
Jose Luis Martinez Lira
Dolores Mendoza Oliva
Arturo Vazquez
Jesus Elvis Cabrera Luviano
Translational Medicine Laboratory, National Cancer Institute, Tlalpan, DF, Mexico
Erika Castillo Gutiérrez
FAICIC Clinical Research, Veracruz, Mexico
Vanessa Rosas Camargo
Cristian Chavez Guerra
Osvaldo Hernandez Flores
David Orta Cortez
Saul Campos
Ivan Romarico González Espinoza
Jessica Reyes Contreras
Angel Gomez Villanueva
Omar Zayas Villanueva