A systematic review and network meta-analysis of phase III randomised controlled trials for adjuvant therapy following resection of pancreatic ductal adenocarcinoma (PDAC).
Journal
HPB : the official journal of the International Hepato Pancreato Biliary Association
ISSN: 1477-2574
Titre abrégé: HPB (Oxford)
Pays: England
ID NLM: 100900921
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
29
10
2019
revised:
28
11
2019
accepted:
02
12
2019
pubmed:
3
1
2020
medline:
26
10
2021
entrez:
3
1
2020
Statut:
ppublish
Résumé
Several randomised controlled trials (RCTs) have reported various systemic adjuvant therapy regimens following resection of pancreatic ductal adenocarcinoma (PDAC). The most commonly applied include modified FOLFRINOX (mFFX), Gemcitabine/Capecitabine (GemCap) and S1, usually compared to gemcitabine (Gem) alone. However, many of these regimens have not been directly compared in RCTs. This network meta-analysis aims to characterise the impact of adjuvant therapies on overall and disease-free survival in patients having resection of PDAC. A systematic review was conducted using MEDLINE, EMBASE, Cochrane Central and American Society of Clinical Oncology (ASCO) abstracts to identify published phase III RCTs articles up to 9th May 2019 that examined adjuvant systemic therapy in resected pancreatic cancer. Data including study characteristics and outcomes including overall survival (OS) and disease-free survival (DFS) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials. Twelve phase III RCTs involving 4947 patients and nine different regimens (5-Flourouracil/Folinic acid (5-FU/FA), Gemcitabine, Gemcitabine/Erlotinib (GemErl), GemCap), mFFX, S1, chemoradiotherapy (CRT), CRT with either 5-FU or Gemcitabine) were identified. S1 was ranked best for overall and disease-free survival followed by mFFX. Whilst there were no significant difference between S1 and mFFX for overall survival (mean difference: 1.6 months, p = 0.8), S1 had significantly longer disease-free survival than mFFX (mean difference: 2.8 months, p < 0.001). Furthermore, S1 was ranked best for lowest overall and haematological grade 3/4 toxicities. This network meta-analysis demonstrates that chemotherapy with S1 or mFFX is superior to GemCap for adjuvant treatment for PDAC, improves survival after surgical resection and should be considered as reasonable standard treatment options in the adjuvant setting and as control arm for future adjuvant clinical trials.
Sections du résumé
BACKGROUND
Several randomised controlled trials (RCTs) have reported various systemic adjuvant therapy regimens following resection of pancreatic ductal adenocarcinoma (PDAC). The most commonly applied include modified FOLFRINOX (mFFX), Gemcitabine/Capecitabine (GemCap) and S1, usually compared to gemcitabine (Gem) alone. However, many of these regimens have not been directly compared in RCTs. This network meta-analysis aims to characterise the impact of adjuvant therapies on overall and disease-free survival in patients having resection of PDAC.
METHODS
A systematic review was conducted using MEDLINE, EMBASE, Cochrane Central and American Society of Clinical Oncology (ASCO) abstracts to identify published phase III RCTs articles up to 9th May 2019 that examined adjuvant systemic therapy in resected pancreatic cancer. Data including study characteristics and outcomes including overall survival (OS) and disease-free survival (DFS) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials.
RESULTS
Twelve phase III RCTs involving 4947 patients and nine different regimens (5-Flourouracil/Folinic acid (5-FU/FA), Gemcitabine, Gemcitabine/Erlotinib (GemErl), GemCap), mFFX, S1, chemoradiotherapy (CRT), CRT with either 5-FU or Gemcitabine) were identified. S1 was ranked best for overall and disease-free survival followed by mFFX. Whilst there were no significant difference between S1 and mFFX for overall survival (mean difference: 1.6 months, p = 0.8), S1 had significantly longer disease-free survival than mFFX (mean difference: 2.8 months, p < 0.001). Furthermore, S1 was ranked best for lowest overall and haematological grade 3/4 toxicities.
CONCLUSION
This network meta-analysis demonstrates that chemotherapy with S1 or mFFX is superior to GemCap for adjuvant treatment for PDAC, improves survival after surgical resection and should be considered as reasonable standard treatment options in the adjuvant setting and as control arm for future adjuvant clinical trials.
Identifiants
pubmed: 31894014
pii: S1365-182X(19)33216-2
doi: 10.1016/j.hpb.2019.12.001
pii:
doi:
Types de publication
Journal Article
Meta-Analysis
Review
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
649-659Informations de copyright
Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.