PURPOSE: This randomized, open -label trial compared the efficacy and safety of adjuvant nabpaclitaxel + 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/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 nabpaclitaxel + 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.
Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial / Tempero, Margaret A.; Pelzer, Uwe; O'Reilly, Eileen M.; Winter, Jordan; Oh, Do-Youn; Li, Chung-Pin; Tortora, Giampaolo; Chang, Heung-Moon; Lopez, Charles D.; Bekaii-Saab, Tanios; Ko, Andrew H.; Santoro, Armando; Park, Joon Oh; Noel, Marcus S.; 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 V.; 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; 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. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 41:11(2023), pp. 2007-2019. [10.1200/jco.22.01134]
Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial
Berardi, RossanaInvestigation
;
2023-01-01
Abstract
PURPOSE: This randomized, open -label trial compared the efficacy and safety of adjuvant nabpaclitaxel + 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/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 nabpaclitaxel + 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.| File | Dimensione | Formato | |
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