Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial
Authors: 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 
Published: December 2022

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.