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; Botirjon Aminjonov; Russell F Palm; Giuseppe Malleo; Ryan K Schmocker; Raëf Abdallah; Changhoon Yoo; Walid L Shaib; Marcel André Schneider; Elena Rangelova; Yoo Jin Choi; Hongbeom Kim; J Bart Rose; Sameer Patel; Gregory C Wilson; Sarah Maloney; Lea Timmermann; Klaus Sahora; Fabian Rössler; Víctor Lopez-Lopez; Emanuel Boyer; Laura Maggino; Thomas Malinka; Jeong Youp Park; Matthew H G Katz; Laura Prakash; Syed A Ahmad; Scott Helton; Jin-Young Jang; Sarah E Hoffe; Roberto Salvia; Julien Taieb; Jin He; Pierre-Alain Clavien; Ulrike Held; Kuno Lehmann

doi:10.1245/s10434-023-13353-2

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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

Authors: Dilmurodjon Eshmuminov ; Botirjon Aminjonov ; Russell F Palm ; Giuseppe Malleo ; Ryan K Schmocker ; Raëf Abdallah ; Changhoon Yoo ; Walid L Shaib ; Marcel André Schneider ; Elena Rangelova ; Yoo Jin Choi ; Hongbeom Kim ; J Bart Rose ; Sameer Patel ; Gregory C Wilson ; Sarah Maloney ; Lea Timmermann ; Klaus Sahora ; Fabian Rössler ; Víctor Lopez-Lopez ; Emanuel Boyer ; Laura Maggino ; Thomas Malinka ; Jeong Youp Park ; Matthew H G Katz ; Laura Prakash ; Syed A Ahmad ; Scott Helton ; Jin-Young Jang ; Sarah E Hoffe ; Roberto Salvia ; Julien Taieb ; Jin He ; Pierre-Alain Clavien ; Ulrike Held ; Kuno Lehmann

Citation: ANNALS OF SURGICAL ONCOLOGY, Vol.30(7) : 4417-4428, 2023-07

Journal Title: ANNALS OF SURGICAL ONCOLOGY

ISSN: 1068-9265

Issue Date: 2023-07

MeSH: Antineoplastic Combined Chemotherapy Protocols / therapeutic use ; Fluorouracil ; Gemcitabine* ; Humans ; Leucovorin / therapeutic use ; Multicenter Studies as Topic ; Neoadjuvant Therapy / adverse effects ; Oxaliplatin / therapeutic use ; Paclitaxel ; Pancreatic Neoplasms* / drug therapy ; Pancreatic Neoplasms* / pathology ; Pancreatic Neoplasms* / surgery

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.