Meta-Analysis

. 2023 Jul;30(7):4417-4428.

doi: 10.1245/s10434-023-13353-2. Epub 2023 Apr 5.

FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review

Dilmurodjon Eshmuminov¹, Botirjon Aminjonov¹, Russell F Palm², Giuseppe Malleo³, Ryan K Schmocker^{4

5}, Raëf Abdallah⁶, Changhoon Yoo⁷, Walid L Shaib⁸, Marcel André Schneider¹, Elena Rangelova^{9

10}, Yoo Jin Choi¹¹, Hongbeom Kim¹¹, J Bart Rose¹², Sameer Patel¹³, Gregory C Wilson¹³, Sarah Maloney¹⁴, Lea Timmermann¹⁵, Klaus Sahora¹⁶, Fabian Rössler¹, Víctor Lopez-Lopez¹⁷, Emanuel Boyer¹⁸, Laura Maggino³, Thomas Malinka¹⁵, Jeong Youp Park¹⁹, Matthew H G Katz²⁰, Laura Prakash²⁰, Syed A Ahmad¹³, Scott Helton²¹, Jin-Young Jang¹¹, Sarah E Hoffe², Roberto Salvia³, Julien Taieb⁶, Jin He⁴, Pierre-Alain Clavien¹, Ulrike Held²², Kuno Lehmann²³

Affiliations

¹ Department of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
² Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
³ Unit of General and Pancreatic Surgery. Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, Italy.
⁴ Department of Surgery, The Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
⁵ Department of Surgery, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.
⁶ Hepatogastroenterology and Gastrointestinal Oncology Department, Hôpital Européen Georges-Pompidou, AGEO (Association des Gastro-Enterologues Oncologues), Université de Paris, SIRIC CARPEM, Paris, France.
⁷ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁸ Department of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
⁹ Department of Upper Gastrointestinal Diseases, Karolinska University Hospital and Department of Clinical Science, Intervention, and Technology (CLINTEC) at Karolinska Institute, Stockholm, Sweden.
¹⁰ Department of Surgery, The Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹¹ Department of Surgery, Seoul National University College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea.
¹² Division of Surgical Oncology, Pancreatobiliary Disease Center at UAB, The University of Alabama at Birmingham, Birmingham, USA.
¹³ Division of Surgical Oncology, Department of Surgery, University of Cincinnati, Cincinnati, OH, USA.
¹⁴ Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia.
¹⁵ Department of Surgery, Charité - Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
¹⁶ Departments of Surgery and Comprehensive Cancer Center, University of Vienna, Medical University of Vienna, Vienna, Austria.
¹⁷ Department of General, Visceral and Transplantation Surgery, Clinic and University Hospital Virgen de la Arrixaca, IMIB-ARRIXACA, Murcia, Spain.
¹⁸ University of South Florida School of Medicine, Tampa, FL, USA.
¹⁹ Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
²⁰ University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²¹ Section of General, Thoracic and Vascular Surgery, Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA.
²² Department of Biostatistics at Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, 8001, Zurich, Switzerland.
²³ Department of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, Switzerland. kuno.lehmann@usz.ch.

PMID: 37020094
PMCID: PMC10250524
DOI: 10.1245/s10434-023-13353-2

Meta-Analysis

FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review

Dilmurodjon Eshmuminov et al. Ann Surg Oncol. 2023 Jul.

. 2023 Jul;30(7):4417-4428.

doi: 10.1245/s10434-023-13353-2. Epub 2023 Apr 5.

Authors

Affiliations

¹ Department of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
² Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
³ Unit of General and Pancreatic Surgery. Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, Italy.
⁴ Department of Surgery, The Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
⁵ Department of Surgery, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.
⁶ Hepatogastroenterology and Gastrointestinal Oncology Department, Hôpital Européen Georges-Pompidou, AGEO (Association des Gastro-Enterologues Oncologues), Université de Paris, SIRIC CARPEM, Paris, France.
⁷ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁸ Department of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
⁹ Department of Upper Gastrointestinal Diseases, Karolinska University Hospital and Department of Clinical Science, Intervention, and Technology (CLINTEC) at Karolinska Institute, Stockholm, Sweden.
¹⁰ Department of Surgery, The Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹¹ Department of Surgery, Seoul National University College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea.
¹² Division of Surgical Oncology, Pancreatobiliary Disease Center at UAB, The University of Alabama at Birmingham, Birmingham, USA.
¹³ Division of Surgical Oncology, Department of Surgery, University of Cincinnati, Cincinnati, OH, USA.
¹⁴ Department of Oncology, Royal North Shore Hospital, Sydney, NSW, Australia.
¹⁵ Department of Surgery, Charité - Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
¹⁶ Departments of Surgery and Comprehensive Cancer Center, University of Vienna, Medical University of Vienna, Vienna, Austria.
¹⁷ Department of General, Visceral and Transplantation Surgery, Clinic and University Hospital Virgen de la Arrixaca, IMIB-ARRIXACA, Murcia, Spain.
¹⁸ University of South Florida School of Medicine, Tampa, FL, USA.
¹⁹ Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
²⁰ University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²¹ Section of General, Thoracic and Vascular Surgery, Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA.
²² Department of Biostatistics at Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, 8001, Zurich, Switzerland.
²³ Department of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, Switzerland. kuno.lehmann@usz.ch.

PMID: 37020094
PMCID: PMC10250524
DOI: 10.1245/s10434-023-13353-2

Abstract

Background: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.

Methods: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.

Results: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.

Conclusions: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

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Figures

**Fig. 2**
Overall survival with pooled, patient-level data for the intention for full treatment population (**A, B**) and non-resected patients (**C, D**) according to treatment regimen groups. *BRPC* borderline resectable pancreatic cancer; *LAPC* locally advanced pancreatic cancer; *FIO* FOLFIRINOX; *GEM/nab* gemcitabine/nab-paclitaxel; GemX gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine; *Gem-mono* gemcitabine as monotherapy; *ITT* full treatment cohort

**Fig. 3**
Overall (**A, B**) and progression-free (**C, D**) survival with pooled patient level data for resected patients, according to treatment regimen groups. *BRPC* borderline resectable pancreatic cancer; *LAPC* locally advanced pancreatic cancer; *FIO* FOLFIRINOX; *GEM/nab* gemcitabine/nab-paclitaxel; *GemX* gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine; *Gem-mono* gemcitabine as monotherapy; *ITT* full treatment cohort

**Fig. 4**
Meta-analysis of resection and R0-resection rates. **a, b:** Resection rates for patients with BRCP or LAPC after FOLFIRINOX or Gemcitabine+. **c, d:** Resection rates in patients with LAPC after FOLFIRINOX or Gemcitabine+. **e, f:** R0 resection rates in patients with BRCP after FOLFIRINOX or Gemcitabine+. **g, h:** R0 resection rates in patients with LAPC after FOLFIRINOX or Gemcitabine+. Overall, we observed a substantial heterogeneity (I²) in all analyses

See this image and copyright information in PMC

Comment in

ASO Author Reflections: Chemotherapy Regimen in Borderline Resectable and Locally Advanced Pancreatic Cancer-Resection Cuts the Deal.
Eshmuminov D, Aminjonov B, Palm RF, Lehmann K. Eshmuminov D, et al. Ann Surg Oncol. 2023 Jul;30(7):4429-4430. doi: 10.1245/s10434-023-13484-6. Epub 2023 Apr 19. Ann Surg Oncol. 2023. PMID: 37074518 Free PMC article. No abstract available.

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FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review

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FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review

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