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NEO-GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Most patients with intrahepatic cholangiocarcinoma (IHCC) develop recurrence after resection. Adjuvant capecitabine remains the standard of care for resected IHCC. A combination of gemcitabine, cisplatin, and nab-paclitaxel (GAP) was associated with a 45% response rate and 20% conversion rate among patients with unresectable biliary tract cancers. The aim of this study was to evaluate the feasibility of delivering GAP in the neoadjuvant setting for resectable, high-risk IHCC.

Methods

A multi-institutional, single-arm, phase II trial was conducted for patients with resectable, high-risk IHCC, defined as tumor size > 5 cm, multiple tumors, presence of radiographic major vascular invasion, or lymph node involvement. Patients received preoperative GAP (gemcitabine 800 mg/m2, cisplatin 25 mg/m2, and nab-paclitaxel 100 mg/m2 on days 1 and 8 of a 21-day cycle) for a total of 4 cycles prior to an attempt at curative-intent surgical resection. The primary endpoint was completion of both preoperative chemotherapy and surgical resection. Secondary endpoints were adverse events, radiologic response, recurrence-free survival (RFS), and overall survival (OS).

Results

Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57–86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection.

Conclusion

Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.

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Acknowledgment

The authors would like to sincerely thank all the patients and families who participated in this clinical trial. Research reported in this publication was supported in part by the Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under Award Number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would like to thank Reham Abdel-Wahab for her assistance in protocol development.

Funding

Bristol Meyers Squibb (Celgene)

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Shishir K. Maithel MD, FACS, FSSO & Jessica M. Keilson MD, MS

  2. Department of Surgical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA

    Hop S. Tran Cao MD

  3. Biostatistics Shared Resource, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Manali Rupji MS & Jeffrey M. Switchenko PhD

  4. Department of Oncology, Mayo Clinic, Rochester, MN, USA

    Amit Mahipal MBBS

  5. Division of Hematology Oncology, Virginia Mason Medical Center, Seattle, WA, USA

    Bruce S. Lin MD

  6. Department of Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA

    Milind M. Javle MD

  7. Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA

    Sean P. Cleary MD

  8. Department of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    Mehmet Akce MD

  9. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Jeffrey M. Switchenko PhD

  10. Division of Surgical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA

    Flavio G. Rocha MD

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  1. Shishir K. Maithel MD, FACS, FSSO
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Correspondence to Shishir K. Maithel MD, FACS, FSSO.

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Disclosure

Flavio G. Rocha, MD: Consultant for Medtronic; Research funding from Gunze; Advisory board member at Astra Zeneca. Bruce S. Lin, MD: Consultant for Exelixis, QED/Helsinn, Pfizer, Bayer, Daiichi-Sankyo; Clinical research support for Exelixis, Zymeworks, Merck, Incyte, Relay Therapeutics. Sean P. Cleary, MD: Consultant for Ethicon. Mehmet Akce, MD: Research funding (to institution) from Tesaro, RedHill Biopharma Limited, Polaris, Bristol-Myers Squibb-Ono Pharmaceutical, Xencor, Merck Sharp & Dohme, Eisai, GSK. Consulting or advisory role at Eisai, Ipsen, Exelixis, GSK, QED, Isofol, Curio Science, AsrtraZeneca, Genentech. Shishir K. Maithel, MD: Research support for clinical trials for Bristol-Myers Squibb. Milind M. Javle, MD: Research funding (to institution) from Merck, EMD Serono, Novartis, Eli Lilly, Astra Zeneca, Genentech, Transthera, Meclun, BMS, Incyte, QED, Taiho, Servier, Oncosil, Basilea, Nucana and to self or as advisory board/ DSMB member from Incyte, Zymeworks, Mundi Pharma, Nucana, MORE health, Agios, Servier, Helsinnn, Transthera, and Origimed.

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Maithel, S.K., Keilson, J.M., Cao, H.S.T. et al. NEO-GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 30, 6558–6566 (2023). https://doi.org/10.1245/s10434-023-13809-5

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