1. Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial
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Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Armando Santoro, Joon Oh Park, Marcus S. Noel, Giovanni Luca Frassineti, Yan-Shen Shan, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Philip Philip, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Stefano Ferrara, Yvan Le Bruchec, George Zhang, Brian Lu, Andrew V. Biankin, Michele Reni, Richard Epstein, Paul Vasey, Jeremy Shapiro, Matthew Burge, Yu Jo Chua, Marion Harris, Nick Pavlakis, Niall Tebbutt, Gerald Prager, Christian Dittrich, Friedrich Längle, Kathrin Philipp-Abbrederis, Richard Greil, Herbert Stöger, Michael Girschikofsky, Thomas Kuehr, Jean-Luc Van Laethem, Stéphanie Laurent, Neesha Dhani, Yoo Joung Ko, Scot Dowden, Petr Kavan, Mustapha Édouard Tehfe, Eugen Kubala, Milan Kohoutek, Per Pfeiffer, Mette Yilmaz, Vibeke Parner, Tapio Salminen, Leena-Maija Soveri, Eija Korkeila, Pia Osterlund, Julien Taieb, David Tougeron, Pascal Artru, François Xavier Caroli-Bosc, Rosine Guimbaud, Antony Turpin, Thomas Walter, Jean Baptiste Bachet, Volker Kunzmann, Florian Kreth, Andreas Block, Marino Venerito, Helmut Oettle, Meinolf Karthaus, Jörg Trojan, Gunnar Folprecht, Markus Lerch, Frank Kullmann, Marcel Reiser, Volker Heinemann, Marcus-Alexander Wörns, Holger Schulz, Benjamin Garlipp, Thomas Yau, Lam Stephen Chan, Balazs Juhasz, László Landherr, Tamas Pinter, György Bodoky, Zsuzsanna Kahán, Raymond McDermott, Derek Power, Luca Gianni, Salvatore Siena, Michele Milella, Alfredo Falcone, Rossana Berardi, Cinzia Bagalà, Francesco Di Costanzo, Fausto Roila, Andrea Ardizzoni, Evaristo Maiello, Silvia Fanello, Johanna Wilmink, Jan Willem de Groot, Geert Creemers, Eduardo Barroso, Tânia Rodrigues, Cristina Sarmento, Cheng Ean Chee, David Tai, Teresa Macarulla Mercade, Manuel Hidalgo Medina, Alfredo Carrato Mena, Joan Maurel Santasusana, Maria Jose Flor Oncala, Carlos Gomez Martin, Rafael Lopez, Andres Muñoz, Ruth Vera Garcia, Inmaculada Ales, Berta Laquente Sáez, Fernando Rivera, Javier Sastre, Cheng-Chung Wu, Yu-Wen Tien, De-Chuan Chan, Tsann-Long Hwang, Jeffry Evans, Jonathan Wadsley, Pippa Corrie, Andrew Biankin, Andrew Ko, Dana Cardin, Elena Chiorean, Johanna Bendell, Anne Noonan, Hedy Kindler, Nishan Fernando, Muhammad Beg, Thomas George, Marcus Noel, Noelle LoConte, Francis Arena, James Posey, Rajat Malhotra, Charles Lopez, Davendra Sohal, Robert McWilliams, Warren Brenner, Mark Womack, Rahul Seth, Renuka lyer, Nathan Bahary, Robert Marsh, Robert Ramirez, Cynthia Chua, James Reeves, Gulam Manji, Anthony El-Khoueiry, Robert Weaver, Vaibhav Sahai, Wells Messersmith, Robert Dreicer, Ahmed Zakari, Andrea Bullock, Benjamin Musher, Mitesh Borad, Edward Kim, David Bajor, Tim Huyck, Hassan Hatoum, Henry Xiong, Boris Pasche, Jill Lacy, Olugbenga Olowokure, Allen Cohn, Donald Richards, Robert Martin, Andrew Paulson, Paul Fanta, Smitha Krishnamurthi, Paul Oberstein, Jyotsna Fuloria, Institut Català de la Salut, [Tempero MA] University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. [Pelzer U] Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. [O'Reilly EM] Memorial Sloan Kettering Cancer Center, New York, NY. [Winter J] Thomas Jefferson University Hospital, Philadelphia, PA. [Oh DY] Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea. [Li CP] Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. [Tabernero J] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Cancer Research ,Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Adjuvants, Immunologic [CHEMICALS AND DRUGS] ,acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::factores inmunitarios::adyuvantes inmunitarios [COMPUESTOS QUÍMICOS Y DROGAS] ,terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Quimioteràpia combinada ,Oncology ,Adjuvants immunològics - Ús terapèutic ,Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,neoplasias::neoplasias::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas::neoplasias::neoplasias por localización::carcinoma ductal pancreático [ENFERMEDADES] ,Pàncrees - Càncer - Tractament ,Neoplasms::Neoplasms::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms::Neoplasms::Neoplasms by Site::Carcinoma, Pancreatic Ductal [DISEASES] ,APACT Investigators - 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.
- Published
- 2023