Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial
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Published:2023-04-10
Issue:11
Volume:41
Page:2007-2019
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Tempero Margaret A.1ORCID, Pelzer Uwe2, O'Reilly Eileen M.3ORCID, Winter Jordan4ORCID, Oh Do-Youn56ORCID, Li Chung-Pin789ORCID, Tortora Giampaolo1011ORCID, Chang Heung-Moon12, Lopez Charles D.13, Bekaii-Saab Tanios14ORCID, Ko Andrew H.1, Santoro Armando1516ORCID, Park Joon Oh17ORCID, Noel Marcus S.18, Frassineti Giovanni Luca19, Shan Yan-Shen20, Dean Andrew21ORCID, Riess Hanno2, Van Cutsem Eric22ORCID, Berlin Jordan23ORCID, Philip Philip2425, Moore Malcolm26, Goldstein David27, Tabernero Josep28ORCID, Li Mingyu29, Ferrara Stefano30, Le Bruchec Yvan30, Zhang George29, Lu Brian29, Biankin Andrew V.313233ORCID, Reni Michele34, Epstein Richard, Vasey Paul, Shapiro Jeremy, Burge Matthew, Chua Yu Jo, Harris Marion, Pavlakis Nick, Tebbutt Niall, Prager Gerald, Dittrich Christian, Längle Friedrich, Philipp-Abbrederis Kathrin, Greil Richard, Stöger Herbert, Girschikofsky Michael, Kuehr Thomas, Van Laethem Jean-Luc, Laurent Stéphanie, Dhani Neesha, Ko Yoo Joung, Dowden Scot, Kavan Petr, Tehfe Mustapha Édouard, Kubala Eugen, Kohoutek Milan, Pfeiffer Per, Yilmaz Mette, Parner Vibeke, Salminen Tapio, Soveri Leena-Maija, Korkeila Eija, Osterlund Pia, Taieb Julien, Tougeron David, Artru Pascal, Caroli-Bosc François Xavier, Guimbaud Rosine, Turpin Antony, Walter Thomas, Bachet Jean Baptiste, Kunzmann Volker, Kreth Florian, Block Andreas, Venerito Marino, Oettle Helmut, Karthaus Meinolf, Trojan Jörg, Folprecht Gunnar, Lerch Markus, Kullmann Frank, Reiser Marcel, Heinemann Volker, Wörns Marcus-Alexander, Schulz Holger, Garlipp Benjamin, Yau Thomas, Chan Lam Stephen, Juhasz Balazs, Landherr László, Pinter Tamas, Bodoky György, Kahán Zsuzsanna, McDermott Raymond, Power Derek, Gianni Luca, Siena Salvatore, Milella Michele, Falcone Alfredo, Berardi Rossana, Bagalà Cinzia, Di Costanzo Francesco, Roila Fausto, Ardizzoni Andrea, Maiello Evaristo, Fanello Silvia, Wilmink Johanna, Willem de Groot Jan, Creemers Geert, Barroso Eduardo, Rodrigues Tânia, Sarmento Cristina, Chee Cheng Ean, Tai David, Mercade Teresa Macarulla, Medina Manuel Hidalgo, Mena Alfredo Carrato, Santasusana Joan Maurel, Flor Oncala Maria Jose, Martin Carlos Gomez, Lopez Rafael, Muñoz Andres, Garcia Ruth Vera, Ales Inmaculada, Sáez Berta Laquente, Rivera Fernando, Sastre Javier, Wu Cheng-Chung, Tien Yu-Wen, Chan De-Chuan, Hwang Tsann-Long, Evans Jeffry, Wadsley Jonathan, Corrie Pippa, Biankin Andrew, Ko Andrew, Cardin Dana, Chiorean Elena, Bendell Johanna, Noonan Anne, Kindler Hedy, Fernando Nishan, Beg Muhammad, George Thomas, Noel Marcus, LoConte Noelle, Arena Francis, Posey James, Malhotra Rajat, Lopez Charles, Sohal Davendra, McWilliams Robert, Brenner Warren, Womack Mark, Seth Rahul, lyer Renuka, Bahary Nathan, Marsh Robert, Ramirez Robert, Chua Cynthia, Reeves James, Manji Gulam, El-Khoueiry Anthony, Weaver Robert, Sahai Vaibhav, Messersmith Wells, Dreicer Robert, Zakari Ahmed, Bullock Andrea, Musher Benjamin, Borad Mitesh, Kim Edward, Bajor David, Huyck Tim, Hatoum Hassan, Xiong Henry, Pasche Boris, Lacy Jill, Olowokure Olugbenga, Cohn Allen, Richards Donald, Martin Robert, Paulson Andrew, Fanta Paul, Krishnamurthi Smitha, Oberstein Paul, Fuloria Jyotsna
Affiliation:
1. University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 2. Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany 3. Memorial Sloan Kettering Cancer Center, New York, NY 4. Thomas Jefferson University Hospital, Philadelphia, PA 5. Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea 6. Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea 7. Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan 8. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 9. School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan 10. Azienda Ospedaliera Universitaria, Verona, Italy 11. Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy 12. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea 13. Oregon Health & Science University, Knight Cancer Institute, Portland, OR 14. Mayo Clinic Cancer Center, Mayo Clinic, Phoenix, AZ 15. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy 16. IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Rozzano, Milan, Italy 17. Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea 18. Division of Hematology/Oncology, Georgetown Lombardi Cancer Center, Washington, DC 19. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 20. Department of Surgery, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan 21. Department of Medical Oncology, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia 22. University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium 23. Vanderbilt-Ingram Cancer Center, Nashville, TN 24. Karmanos Cancer Institute, Detroit, MI 25. Henry Ford Cancer Institute, Detroit, MI 26. Princess Margaret Hospital, Toronto, Ontario, Canada 27. Nelune Cancer Center, Prince of Wales Hospital, University of New South Wales, Randwick, New South Wales, Australia 28. Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, Barcelona, Spain 29. Bristol Myers Squibb, Princeton, NJ 30. Celgene Research SLU, a Bristol Myers Squibb Company, Boudry, Switzerland 31. Wolfson Wohl Cancer Research Center, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom 32. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom 33. South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales, Australia 34. IRCCS Ospedale San Raffaele Vita e Salute University, Milan, Italy
Abstract
PURPOSE 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 ). METHODS 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. RESULTS 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. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
42 articles.
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