TY - JOUR
T1 - Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma
T2 - Results from a Randomized, Open-Label, Phase III Trial
AU - APACT Investigators
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 - 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 - Dhani, Neesha
N1 - 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.
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U2 - 10.1200/JCO.22.01134
DO - 10.1200/JCO.22.01134
M3 - Article
C2 - 36521097
AN - SCOPUS:85151492442
SN - 0732-183X
VL - 41
SP - 2007
EP - 2019
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -