Adjuvant nab -Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial
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Tempero, Margaret | Pelzer, Uwe | O'Reilly, Eileen | Winter, Jordan | Oh, Do-Youn | Li, Chung-Pin | Tortora, Giampaolo | Chang, Heung-Moon | Lopez, Charles | Bekaii-Saab, Tanios | Ko, Andrew | Santoro, Armando | Park, Joon Oh | Noel, Marcus | Frassineti, Giovanni Luca | Shan, Yan-Shen | Dean, Andrew | Riess, Hanno | van Cutsem, Eric | Berlin, Jordan | Philip, Philip | Moore, Malcolm | Goldstein, David | Tabernero, Josep | Li, Mingyu | Ferrara, Stefano | Le Bruchec, Yvan | Zhang, George | Lu, Brian | Biankin, Andrew | Reni, Michele | 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 | Cardin, Dana | Chiorean, Elena | Bendell, Johanna | Noonan, Anne | Kindler, Hedy | Fernando, Nishan | Beg, Muhammad | George, Thomas | Loconte, Noelle | Arena, Francis | Posey, James | Malhotra, Rajat | 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
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CCSD ; American Society of Clinical Oncology -
International audience.
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/m 2 ) + gemcitabine (1,000 mg/m 2 ) 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.
