Author(s): Margaret A. Tempero, MD1; Uwe Pelzer, MD2; Eileen M. O’Reilly, MD3; Jordan Winter, MD4; Do-Youn Oh, MD5,6; Chung-Pin Li, MD, PhD7,8,9; Giampaolo Tortora, MD10,11; Heung-Moon Chang, MD12; Charles D. Lopez, MD, PhD13; Tanios Bekaii-Saab, MD14; Andrew H. Ko, MD1; Armando Santoro, MD15,16; Joon Oh Park, MD, PhD17; Marcus S. Noel, MD18; Giovanni Luca Frassineti, MD19; Yan-Shen Shan, MD, PhD20; Andrew Dean, MD21; Hanno Riess, MD2; Eric Van Cutsem, MD, PhD22; Jordan Berlin, MD23; Philip Philip, MD24,25; Malcolm Moore, MD26; David Goldstein, MD27; Josep Tabernero, MD, PhD28; Mingyu Li, PhD29; Stefano Ferrara, PharmD30; Yvan Le Bruchec, MS30; George Zhang, PhD29; Brian Lu, MD, PhD29; Andrew V. Biankin, MD, PhD31,32,33; and Michele Reni, MD34
This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430).
We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety.
Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 (nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 (nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent (nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events.
The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
Author Affiliations1University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA2Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany3Memorial Sloan Kettering Cancer Center, New York, NY4Thomas Jefferson University Hospital, Philadelphia, PA5Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea6Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea7Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan8Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan9School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan10Azienda Ospedaliera Universitaria, Verona, Italy11Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy12Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea13Oregon Health & Science University, Knight Cancer Institute, Portland, OR14Mayo Clinic Cancer Center, Mayo Clinic, Phoenix, AZ15Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy16IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Rozzano, Milan, Italy17Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea18Division of Hematology/Oncology, Georgetown Lombardi Cancer Center, Washington, DC19Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy20Department of Surgery, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan21Department of Medical Oncology, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia22University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium23Vanderbilt-Ingram Cancer Center, Nashville, TN24Karmanos Cancer Institute, Detroit, MI25Henry Ford Cancer Institute, Detroit, MI26Princess Margaret Hospital, Toronto, Ontario, Canada27Nelune Cancer Center, Prince of Wales Hospital, University of New South Wales, Randwick, New South Wales, Australia28Vall d’Hebron Hospital Campus and Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, Barcelona, Spain29Bristol Myers Squibb, Princeton, NJ30Celgene Research SLU, a Bristol Myers Squibb Company, Boudry, Switzerland31Wolfson Wohl Cancer Research Center, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom32West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom33South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales, Australia34IRCCS Ospedale San Raffaele Vita e Salute University, Milan, Italyon behalf of the APACT Investigators