Adjuvant <i>nab</i> -Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial
Margaret A. Tempero, Uwe Pelzer, Eileen M. O’Reilly, Jordan M. 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 Smith Noel, Giovanni Luca Frassineti, Yan‐Shen Shan, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Philip Philip, Malcolm J. Moore, David Goldstein, Josep Tabernero, Mingyu Li, Stefano Ferrara, Yvan Le Bruchec, George Zhang, Brian Lu, Andrew V. Biankin, Michele Reni, Richard A. Epstein, Paul L. Vasey, Jeremy Shapiro, Matthew Burge, Yu Jo Chua, Marion Harris, Nick Pavlakis, Niall C. Tebbutt, Gerald W. Prager, Christian Dittrich, Friedrich Längle, Kathrin Philipp‐Abbrederis, Richard Greil, Herbert Stöger, Michael Girschikofsky, Thomas Kuehr, Jean–Luc Van Laethem, Stéphanie Laurent, Neesha C. Dhani, Yoo Joung Ko, Scot Dowden, Petr Kavan, Mustapha Édouard Tehfe, Eugen Kubala, Milan Kohoutek, Per Pfeiffer, Mette Yilmaz, Vibeke K. Parner, Tapio Salminen, Leena‐Maija Soveri, Eija Korkeila, Pia Österlund, Julien Taı̈eb, David Tougeron, Pascal Artru, François‐Xavier Caroli‐Bosc, Rosine Guimbaud, Antony Turpin, Thomas Walter, Jean‐Baptiste Bachet, Volker Kunzmann, Florian Kreth, Andreas De Block, Marino Venerito, Helmut Oettle, Meinolf Karthaus, Jörg Trojan, Gunnar Folprecht, Markus M. Lerch, Frank Kullmann, Marcel Reiser, Volker Heinemann, Marcus‐Alexander Wörns, H. Schulz, Benjamin Garlipp, Thomas Yau, Lam Stephen Chan, Balázs Juhász, László Landherr, Tamás Pintér, G. Bodoky, Zsuzsanna Kahán, Raymond McDermott, Derek G. Power, Luca Gianni, Salvatore Siena, Michèle Milella, Alfredo Falcone, Rossana Berardi
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/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.