TY - JOUR
T1 - Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma
T2 - Results from a Randomized, Open-Label, Phase III Trial
AU - Tempero, Margaret A.
AU - Pelzer, Uwe
AU - O'Reilly, Eileen M.
AU - Winter, Jordan
AU - Oh, Do-Youn
AU - Li, Chung-Pin
AU - Tortora, Giampaolo
AU - Chang, Heung-Moon
AU - Lopez, Charles D.
AU - Bekaii-Saab, Tanios
AU - Ko, Andrew H.
AU - Santoro, Armando
AU - Park, Joon Oh
AU - Noel, Marcus S.
AU - Frassineti, Giovanni Luca
AU - Shan, Yan-Shen
AU - Dean, Andrew
AU - Riess, Hanno
AU - van Cutsem, Eric
AU - Berlin, Jordan
AU - Philip, Philip
AU - Moore, Malcolm
AU - Goldstein, David
AU - Tabernero, Josep
AU - Li, Mingyu
AU - Ferrara, Stefano
AU - le Bruchec, Yvan
AU - Zhang, George
AU - Lu, Brian
AU - Biankin, Andrew V.
AU - Reni, Michele
AU - APACT Investigators
AU - Epstein, Richard
AU - Vasey, Paul
AU - Shapiro, Jeremy
AU - Burge, Matthew
AU - Chua, Yu Jo
AU - Harris, Marion
AU - Pavlakis, Nick
AU - Tebbutt, Niall
AU - Prager, Gerald
AU - Dittrich, Christian
AU - Längle, Friedrich
AU - Philipp-Abbrederis, Kathrin
AU - Greil, Richard
AU - Stöger, Herbert
AU - Girschikofsky, Michael
AU - Kuehr, Thomas
AU - van Laethem, Jean-Luc
AU - Laurent, Stéphanie
AU - Wilmink, Johanna
N1 - Funding Information: Supported by Bristol Myers Squibb and by Celgene, a Bristol Myers Squibb Company, Princeton, NJ. Professional medical writing and editorial assistance was provided by Narender Dhingra, MBBS, PhD, CMPP, of Meditech Media, Ltd; Aaron Runkle, PhD, CMPP, of Meditech Media, Ltd; and Krystin Tran, PharmD, of Chrysalis Medical Communications LLC and funded by Bristol Myers Squibb. Medical review was supported by Julie Jeanes, Emily Mantovani, Desmond McGovern, Alfredo Romano, David Eardley, and Lotus Yung. Publisher Copyright: © American Society of Clinical Oncology.
PY - 2023/4/10
Y1 - 2023/4/10
N2 - 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).METHODSWe 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.RESULTSTwo 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.CONCLUSIONThe primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
AB - 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).METHODSWe 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.RESULTSTwo 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.CONCLUSIONThe primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
UR - http://www.scopus.com/inward/record.url?scp=85151492442&partnerID=8YFLogxK
U2 - https://doi.org/10.1200/JCO.22.01134
DO - https://doi.org/10.1200/JCO.22.01134
M3 - Article
C2 - 36521097
SN - 0732-183X
VL - 41
SP - 2007
EP - 2019
JO - Journal of clinical oncology
JF - Journal of clinical oncology
IS - 11
ER -