Perioperative or adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer: Updated final results of the randomized phase II AIO-NEONAX trial.

Authors

Thomas Ettrich

Thomas Jens Ettrich

Ulm University Hospital, Department of Internal Medicine I, Ulm, Germany

Thomas Jens Ettrich , Waldemar Uhl , Marko Kornmann , Hana Algül , Helmut Friess , Alexander Koenig , Eike Gallmeier , Manfred P. Lutz , Kai Wille , Carl Christoph Schimanski , Volker Kunzmann , Michael Geissler , Dirk Waldschmidt , Severin Daum , Lisa Blome , Andrea Tannapfel , Lukas Perkhofer , Margaret A. Tempero , Anke C. Reinacher-Schick , Thomas Seufferlein

Organizations

Ulm University Hospital, Department of Internal Medicine I, Ulm, Germany, Ruhr-University Bochum, St. Josef Hospital, Bochum, Germany, Department of Surgery, University of Ulm, Ulm, Germany, Technische Universität München, Comprehensive Cancer Center Munich-TUM and Department of Internal Medicine II, Munich, Germany, Technical University Munich, Klinikum rechts der Isar, Surgical Clinic and Policlinic, Munich, Germany, University Medical Center Goettingen, Department of Gastroenterology, Gastrointestinal Oncology, and Endocrinology, Goettingen, Germany, Department of Gastroenterology and Endocrinology, Uniklinikum Giessen und Marburg, Marburg, Germany, Caritasklinik St. Theresia, Saarbruecken, Germany, University Hospital Ruhr-University-Bochum, Minden, Germany, Klinikum Darmstadt GmbH and Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Darmstadt and Mainz, Germany, Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II and Comprehensive Cancer Center Mainfranken, Würzburg, Germany, Klinikum Esslingen, Department of Hematology/Oncology, Esslingen, Germany, Department of Gastroenterology and Hepatology, University of Cologne, Cologne, Germany, Charité-University Medicine Berlin, Berlin, Germany, Biometrics, ClinAssess Gesellschaft für klinische Forschung mbH, Leverkusen, Germany, Institut für Pathologie der Ruhr-Universität Bochum, Bochum, Germany, Ulm University, Department of Internal Medicine I, Ulm, Germany, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany, Hospital of the University Ulm, Ulm, Germany

Research Funding

Pharmaceutical/Biotech Company

Background: Perioperative chemotherapy (CTX) in resectable pancreatic ductal adenocarcinoma (PDAC) is still not considered standard of care and data are limited. The NEONAX trial examined gemcitabine (Gem) plus nab-paclitaxel (nab-P), in the perioperative or adjuvant therapy of resectable PDAC (NCCN criteria). Methods: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. 127 resectable PDAC patients in 22 German centers were randomized 1:1 to perioperative (2 pre- and 4 postoperative cycles, arm A) or adjuvant (6 cycles, arm B) of Gem (1000mg/m2) and nab-P (125mg/m2) on days 1,8,15 of a 28-day cycle. Results: We previously reported the primary endpoint disease free survival (DFS) at 18 mo. in the modified intention-to-treat (ITT)-population (defined as R0/R1 resected pts. that either started neoadjuvant (A) or adjuvant (B) CTX. The pre-defined DFS rate of 55% at 18 mo. was not reached in both arms (A: 32.2%, B: 41.4%). Here we present the final results of the secondary endpoints median overall survival (mOS), pN0-resection rate, perioperative morbidity/mortality and safety in the ITT-population. Most common grade ≥3 treatment emergent adverse events in the safety population were neutropenia (arm A 21.1%, arm B 12.3%), fatigue (arm A 8.8%, arm B 5.3%) and anemia (arm A 10.5%, arm B 1.8%). The most frequent post-/perioperative complications of all grades in pts. undergoing resection were infections (arm A: 24.4%, arm B: 8.8%), pancreatic fistulas (arm A: 14.6%; arm B: 13.3%) and bleedings (arm A: 9.7%; arm B: 6.7%). Perioperative mortality was 2.4% in the neoadjuvant and 6.7% in the upfront surgery setting. The median number of resected lymph nodes was comparable in both arms (A: n = 21, B: n = 26). The pN0-resection rate was 33.3% in the neoadjuvant/perioperative arm A and 29.5% in the upfront surgery arm B. R0 resection rates were 87.8% in arm A and 67.4% in arm B, respectively. Median OS as a key secondary endpoint in the ITT population was 25.2 mo. in arm A and 16.7 mo. for upfront surgery, a difference of 8.5 mo. This difference corresponds to a mDFS of 11.5 mo. in arm A and 5.9 mo. in arm B. 91.5% of pts. in arm A started and 84.7% completed neoadjuvant CTX but only 42.4% of pts. in arm B started adjuvant CTX. Conclusions: Perioperative treatment with Gem/nab-P was well tolerated and showed an encouraging mOS of 25.2 mo., this is well in the range of the data in SWOG 1505 (23.6 mo.) or PREOPANC (15.7 mo.). The corresponding mOS in the upfront surgery arm was 16.7 mo. The 8.5 mo. difference may be explained by the fact that many pts. in arm B did not receive adjuvant treatment whereas the vast majority of pts. in arm A completed at least preoperative CTX. Neoadjuvant/perioperative treatment is a promising novel option for pts. with resectable PDAC. The optimal treatment regimen is subject of current clinical trials. Clinical trial information: NCT02047513.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Pancreatic Cancer

Clinical Trial Registration Number

NCT02047513

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 4133)

DOI

10.1200/JCO.2022.40.16_suppl.4133

Abstract #

4133

Poster Bd #

119

Abstract Disclosures