Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial

Author(s): Daniel H. Palmer, PhD¹; Richard Jackson, PhD¹; Christoph Springfeld, MD^2,3; Paula Ghaneh, MD¹; Charlotte Rawcliffe, MSc¹; Christopher M. Halloran, MD¹; Olusola Faluyi, MD⁴; David Cunningham, MD⁵; Jonathan Wadsley, MD⁶; Suzanne Darby, MD⁷; Tim Meyer, MD⁸; Roopinder Gillmore, MD⁹; Pehr Lind, PhD^10,11; Bengt Glimelius, MD¹²; Stephen Falk, MD¹³; Yuk Ting Ma, MD¹⁴; Gary William Middleton, MD¹⁴; Sebastian Cummins, MD¹⁵; Paul J. Ross, MD¹⁶; Harpreet Wasan, MD¹⁷; Alec McDonald, MD¹⁸; Tom Crosby, MD¹⁹; Pascal Hammel, MD, PhD²⁰; David Borg, PhD^21,22; Sharmila Sothi, MD²³; Juan W. Valle, MD²⁴; Arianeb Mehrabi, MD²⁵; Peter Bailey, PhD^3,26; Christine Tjaden, MD²⁷; Christoph Michalski, MD²⁵; Thilo Hackert, MD²⁸; Markus W. Büchler, MD^3,25; John P. Neoptolemos, MD^3,25

Source: https://doi.org/10.1200/JCO.24.01118

Dr. Maen Hussein's Thoughts

I recall this trial well, in node-negative pancreatic cancer GemCap is a better option than gemcitabine alone in patients who can’t be treated with mFOLFIRINOX with improved five-year overall survival (OS) 59 vs 53%, hazard ratio (HR) 0.63.

PURPOSE

The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria. Our aim was to analyze the ESPAC4 survival on long-term follow-up.

METHODS

The OS of 732 ESPAC4 patients comparing 367 randomly assigned to gemcitabine and 365 to GemCap was previously reported after a median follow-up time of 43.2 months (95% CI, 39.7 to 45.5) and 458 deaths. Analysis was now carried out after a median follow-up of 104 months (101-108) and 566 deaths.

RESULTS

The median OS was 29.5 months (27.5-32.1) for all patients, 28.4 months (25.2-32.0) in the gemcitabine group and 31.6 months (26.5-38.0) in the GemCap group (hazard ratio [HR], 0.83 [0.71 to 0.98]; P = .031). R0 patients given gemcitabine had a median survival of 32.2 months (27.9-41.6) compared with 49.9 months (39.0-82.3) for those given GemCap (HR, 0.63 [0.47 to 0.84]; P = .002). Lymph node-negative patients had significantly higher 5 year OS rates on GemCap (59% [49%-71%]) than gemcitabine (53% [42%-66%]; HR, 0.63 [0.41 to 0.98]; P = .04) but not those with positive lymph nodes (P = .225). The OS advantage for GemCap was retained in the PRODIGE24 subgroup of 193 (26.4%) ESPAC4 patients not eligible for PRODIGE24 with a median survival of 20.7 (16.2-27.3) months in patients allocated to gemcitabine compared with 25.9 (22.3-30.2) months for ineligible patients allocated to GemCap (HR, 0.71 [95% CI, 0.52 to 0.98]; χ2log-rank-1df = 4.31; P = .038).

CONCLUSION

GemCap is a standard option for patients not eligible for mFOLFIRINOX. Exploratory evidence suggests that GemCap may be particularly efficacious in R0 patients and also in lymph node-negative patients.

Author Affiliations

¹University of Liverpool, Liverpool, United Kingdom;²Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany;³Champalimaud Foundation, Lisbon, Portugal;⁴The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, United Kingdom;⁵Royal Marsden Hospital, London, United Kingdom;⁶Weston Park Cancer Centre, Sheffield, United Kingdom;⁷Weston Park Hospital, Sheffield, United Kingdom;⁸Department of Oncology, Royal Free Hospital and UCL Cancer Institute, University College London, London, United Kingdom;⁹Royal Free Hospital, London, United Kingdom;¹⁰Department of Oncology, Stockholm Söder Hospital, Stockholm, Sweden;¹¹Karolinska Institute, Stockholm, Sweden;¹²Department of Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden;¹³Bristol Cancer Institute, Bristol, United Kingdom;¹⁴University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom;¹⁵Royal Surrey County Hospital, Guildford, United Kingdom;¹⁶Guy’s & St Thomas’ and King’s College Hospitals, London, United Kingdom;¹⁷Hammersmith Hospital, London, United Kingdom;¹⁸The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom;¹⁹Velindre Cancer Centre, Cardiff, United Kingdom;²⁰Hôpital Paul Brousse (APHP), Paris-Saclay University, Villejuif, France;²¹Skåne University Hospital, Lund, Sweden;²²Department of Clinical Sciences Lund, Oncology and Therapeutic Pathology, Lund University, Lund, Sweden;²³University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom;²⁴Cholangiocarcinoma Foundation, Herriman, UT;²⁵Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany;²⁶Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany;²⁷MRI TUM, Klinikum rechts der Isar of the Technical University of Munich, Munich, Germany;²⁸Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany

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