The AGITG GAP Study: A Phase II Study of Perioperative Gemcitabine and Nab-Paclitaxel for Resectable Pancreas Cancer

Abstract

Background

While combination therapy with nab-paclitaxel/gemcitabine (nab-gem) is effective in pancreatic ductal adenocarcinoma (PDAC), its efficacy as perioperative chemotherapy is unknown. The primary objective of this multicenter, prospective, single-arm, phase II study was to determine whether neoadjuvant therapy with nab-gem was associated with higher complete resection rates (R0) in resectable PDAC, while the secondary objectives were to determine the utility of radiological assessment of response to preoperative chemotherapy and the safety and efficacy of nab-gem as perioperative therapy.

Methods

Patients were recruited from eight Australian sites, and 42 patients with radiologically defined resectable PDAC and an Eastern Cooperative Oncology Group performance status of 0–2 were enrolled. Participants received two cycles of preoperative nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 on days 1, 8, and 15 (28-day cycle) presurgery, and four cycles postoperatively. Early response to chemotherapy was measured with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans on day 15.

Results

Preoperative nab-gem was completed by 93% of participants, but only 63% postoperatively. Thirty-six patients had surgery: 6 (17%) were unresectable, 15 (52%) had R0 (≥ 1 mm) resections, 14 (48%) had R1 (< 1 mm) resections, and 1 patient did not have PDAC. Median progression-free survival was 12.3 months and median overall survival (OS) was 23.5 months: R0 patients had an OS of 35 months versus 25.6 months for R1 patients after surgery. Seven patients had not progressed after 43 months.

Conclusions

The GAP trial demonstrated that perioperative nab-gem was tolerable. Although the primary endpoint of an 85% R0 rate was not met, the R0 rate was similar to trials using a > 1 mm R0 resection definition, and survival rates were comparable with recent adjuvant studies.

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GAP Investigators

Trial Management Committee: A. Barbour (chair), D. Goldstein, J.S. Samra, M. Harris, Y.J. Chua, M. Burge, N. O’Rourke, S. Yip, V. Gebski, J. Simes, R. Hicks.

Independent Data Safety Monitoring Committee: A. Coates (chair), H. Gurney, V. Do, I. Marschner.

Clinical Trials Centre: J. Mitchell, M. Donoghoe, V. Gebski, J. Simes, S. Goldstone, S. Yip, J. Simes.

Participating Medical Oncologists: Y.J. Chua (The Canberra Hospital, Canberra, ACT, Australia), N. Pavlakis (Royal North Shore Hospital, Sydney, NSW, Australia), D. Goldstein (Prince of Wales Hospital, Sydney, NSW, Australia), M. Aghmesheh (Southern Medical Day Care Centre, Woolongong, NSW, Australia), M. Burge (Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia), W. Joubert (Icon Cancer Care Wesley, Brisbane, QLD, Australia), D. Grimes (Greenslopes Private Hospital, Brisbane, QLD, Australia), M. Harris (Monash Medical Centre, Melbourne, VIC, Australia).

Participating Surgeons: J.S. Samra, K.S. Haghighi, P. Truskett, S. Bagia, M. Jaber (Sydney, NSW, Australia); S. Gananadha (Canberra, ACT, Australia); N. O’Rourke, R. Bryant, L. Nathanson, D. Cavallucci, A. Barbour, J. Fawcett, T. O’Rourke (Brisbane, QLD, Australia); D. Croagh, R. Jones (Melbourne, VIC, Australia).

Funding

Specialized Therapeutics Australia provided funding support and supplied nab‐paclitaxel; gemcitabine was available on the Pharmaceutical Benefits Scheme (PBS). This study was partly funded by the GAP-T NHMRC Project Grant (APP1026563). Trial management and statistical support was undertaken by the NHMRC-CTC. The AGITG was the legal sponsor and the trial was registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12611000848909). The GAP study was conducted under the auspices of the AGITG, the legal sponsor, independently of the funders. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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AB and DG had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study Concept and Design: Barbour, Gebski, Kench, Goldstein. Acquisition, Analysis, or Interpretation of Data: All authors. Drafting of the Manuscript: Barbour, Goldstein, Donoghoe, Gebski, Chan. Critical Revision of the Manuscript for Important Intellectual Content: All authors. Statistical Analysis: Donoghoe, Gebski. Obtained Funding: Barbour, Goldstein, Kench. Administrative, Technical, or Material Support: Barbour, Goldstein, Mitchell, Chan. Study Supervision: Barbour, Goldstein, Mitchell, Chan, Chua, Samra, Burge, Harris, O’Rourke, Kench. Additional Contributions: John Simes from the CTC provided input into the study concept and design, critical revision of the manuscript, and statistical advice. Jonathon Fawcett from the Queensland Liver Transplant Service, Brisbane, QLD, Australia, provided independent assessment of pathology reports. Sherilyn Goldstone from the CTC assisted with manuscript preparation, and Chris Brown from the CTC is acknowledged for statistical work. Manju Chandrasegaram, AGITG Research Fellow and Hepatopancreatobiliary (HPB) and General Surgeon reviewed the surgical literature to inform this paper. These people were not specifically compensated for their work. Local investigators, surgeons, and data managers gathered the data, which were submitted to the CTC in Sydney, NSW, Australia, via an electronic data collection system.

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Correspondence to Andrew P. Barbour MBBS PhD FRACS FACS.

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Barbour, A.P., Samra, J.S., Haghighi, K.S. et al. The AGITG GAP Study: A Phase II Study of Perioperative Gemcitabine and Nab-Paclitaxel for Resectable Pancreas Cancer. Ann Surg Oncol 27, 2506–2515 (2020). https://doi.org/10.1245/s10434-020-08205-2

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