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

Author(s): Margaret A. Tempero, MD¹; Uwe Pelzer, MD²; Eileen M. O’Reilly, MD³; Jordan Winter, MD⁴; Do-Youn Oh, MD^5,6; Chung-Pin Li, MD, PhD^7,8,9; Giampaolo Tortora, MD^10,11; Heung-Moon Chang, MD¹²; Charles D. Lopez, MD, PhD¹³; Tanios Bekaii-Saab, MD¹⁴; Andrew H. Ko, MD¹; Armando Santoro, MD^15,16; Joon Oh Park, MD, PhD¹⁷; Marcus S. Noel, MD¹⁸; Giovanni Luca Frassineti, MD¹⁹; Yan-Shen Shan, MD, PhD²⁰; Andrew Dean, MD²¹; Hanno Riess, MD²; Eric Van Cutsem, MD, PhD²²; Jordan Berlin, MD²³; Philip Philip, MD^24,25; Malcolm Moore, MD²⁶; David Goldstein, MD²⁷; Josep Tabernero, MD, PhD²⁸; Mingyu Li, PhD²⁹; Stefano Ferrara, PharmD³⁰; Yvan Le Bruchec, MS³⁰; George Zhang, PhD²⁹; Brian Lu, MD, PhD²⁹; Andrew V. Biankin, MD, PhD^31,32,33; and Michele Reni, MD³⁴

Source: DOI: 10.1200/JCO.22.01134 Journal of Clinical Oncology 41, no. 11 (April 10, 2023) 2007-2019.

Dr. Maen Hussein's Thoughts

Somewhat disappointing as this was a negative study, however it is still an option for patients who are not candidates for mFOLFIRINOX.

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.

Author Affiliations

¹University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA²Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany³Memorial Sloan Kettering Cancer Center, New York, NY⁴Thomas Jefferson University Hospital, Philadelphia, PA⁵Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea⁶Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea⁷Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan⁸Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan⁹School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan¹⁰Azienda Ospedaliera Universitaria, Verona, Italy¹¹Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy¹²Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea¹³Oregon Health & Science University, Knight Cancer Institute, Portland, OR¹⁴Mayo Clinic Cancer Center, Mayo Clinic, Phoenix, AZ¹⁵Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy¹⁶IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Rozzano, Milan, Italy¹⁷Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea¹⁸Division of Hematology/Oncology, Georgetown Lombardi Cancer Center, Washington, DC¹⁹Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy²⁰Department of Surgery, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan²¹Department of Medical Oncology, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia²²University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium²³Vanderbilt-Ingram Cancer Center, Nashville, TN²⁴Karmanos Cancer Institute, Detroit, MI²⁵Henry Ford Cancer Institute, Detroit, MI²⁶Princess Margaret Hospital, Toronto, Ontario, Canada²⁷Nelune Cancer Center, Prince of Wales Hospital, University of New South Wales, Randwick, New South Wales, Australia²⁸Vall d’Hebron Hospital Campus and Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, Barcelona, Spain²⁹Bristol Myers Squibb, Princeton, NJ³⁰Celgene Research SLU, a Bristol Myers Squibb Company, Boudry, Switzerland³¹Wolfson Wohl Cancer Research Center, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom³²West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom³³South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales, Australia³⁴IRCCS Ospedale San Raffaele Vita e Salute University, Milan, Italyon behalf of the APACT Investigators

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