Adjuvant nab-paclitaxel + gemcitabine in resected pancreatic ductal adenocarcinoma: results from a randomized, open-label, phase III trial

Tempero, M. A. et al. (2023) Adjuvant nab-paclitaxel + gemcitabine in resected pancreatic ductal adenocarcinoma: results from a randomized, open-label, phase III trial. Journal of Clinical Oncology, 41(11), pp. 2007-2019. (doi: 10.1200/JCO.22.01134) (PMID:36521097) (PMCID:PMC10082313)

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/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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Biankin, Professor Andrew
• Authors: Tempero, M. A., Pelzer, U., O'Reilly, E. M., Winter, J., Oh, D.-Y., Li, C.-P., Tortora, G., Chang, H.-M., Lopez, C. D., Bekaii-Saab, T., Ko, A. H., Santoro, A., Park, J. O., Noel, M. S., Frassineti, G. L., Shan, Y.-S., Dean, A., Riess, H., Van Cutsem, E., Berlin, J., Philip, P., Moore, M., Goldstein, D., Tabernero, J., Li, M., Ferrara, S., Le Bruchec, Y., Zhang, G., Lu, B., Biankin, A. V., and Reni, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Clinical Oncology
• Publisher: American Society of Clinical Oncology
• ISSN: 0732-183X
• ISSN (Online): 1527-7755
• Published Online: 15 December 2022
• Copyright Holders: Copyright © 2022 American Society of Clinical Oncology
• First Published: First published in Journal of Clinical Oncology 41(11): 2007-2019
• Publisher Policy: Reproduced under a Creative Commons License