Impact of completeness of adjuvant gemcitabine, relapse pattern, and subsequent therapy on outcome of patients with resected pancreatic ductal adenocarcinoma - A pooled analysis of CONKO-001, CONKO-005, and CONKO-006 trials.
Adult
Aged
Aged, 80 and over
Antigens, Tumor-Associated, Carbohydrate
/ blood
Antimetabolites, Antineoplastic
/ adverse effects
Carcinoma, Pancreatic Ductal
/ blood
Chemotherapy, Adjuvant
Databases, Factual
Deoxycytidine
/ adverse effects
Disease-Free Survival
Female
Humans
Lung Neoplasms
/ mortality
Male
Middle Aged
Neoplasm Recurrence, Local
Palliative Care
Pancreatectomy
/ adverse effects
Pancreatic Neoplasms
/ blood
Randomized Controlled Trials as Topic
Retrospective Studies
Risk Assessment
Risk Factors
Time Factors
Young Adult
Gemcitabine
Liver metastasis
Lung metastasis
Metastatic pancreatic cancer
Overall survival
Relapse patterns
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
29
12
2020
revised:
13
03
2021
accepted:
22
03
2021
pubmed:
4
5
2021
medline:
26
10
2021
entrez:
3
5
2021
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) represents one of the most fatal malignancies worldwide. It is suggested that survival in PDAC depends, among other things, on pattern of disease recurrence. We performed a pooled analysis of the adjuvant therapy studies CONKO-001, CONKO-005, and CONKO-006, including a total of 912 patients with regard to prognostic factors in patients with recurrent disease. Overall survival from disease recurrence (OS 2) and disease-free survival (DFS) from the day of surgery were expressed by Kaplan-Meier method and compared using log-rank testing and Cox regression. Of 912 patients treated within the previously mentioned CONKO trials, we identified 689 patients with disease recurrence and defined site of relapse. In multivariable analysis, the presence of isolated pulmonary metastasis, low tumour grading, and low postoperative level of CA 19-9 remained significant factors for improved OS 2 and DFS. Furthermore, completeness of adjuvant gemcitabine-based treatment (OS 2: P = 0.006), number of relapse sites (OS 2: P = 0.015), and type of palliative first-line treatment (OS 2: P < 0.001) significantly affected overall survival after disease recurrence in PDAC. Determining tumour subgroups using prognostic factors may be helpful to stratify PDAC patients for future clinical trials. In case of disease recurrence, the site of relapse may have a prognostic impact on subsequent survival. Further investigations are needed to identify differences in tumour biology, reflecting relapse patterns and the differing survival of PDAC patients.
Sections du résumé
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) represents one of the most fatal malignancies worldwide. It is suggested that survival in PDAC depends, among other things, on pattern of disease recurrence.
PATIENTS AND METHODS
We performed a pooled analysis of the adjuvant therapy studies CONKO-001, CONKO-005, and CONKO-006, including a total of 912 patients with regard to prognostic factors in patients with recurrent disease. Overall survival from disease recurrence (OS 2) and disease-free survival (DFS) from the day of surgery were expressed by Kaplan-Meier method and compared using log-rank testing and Cox regression.
RESULTS
Of 912 patients treated within the previously mentioned CONKO trials, we identified 689 patients with disease recurrence and defined site of relapse. In multivariable analysis, the presence of isolated pulmonary metastasis, low tumour grading, and low postoperative level of CA 19-9 remained significant factors for improved OS 2 and DFS. Furthermore, completeness of adjuvant gemcitabine-based treatment (OS 2: P = 0.006), number of relapse sites (OS 2: P = 0.015), and type of palliative first-line treatment (OS 2: P < 0.001) significantly affected overall survival after disease recurrence in PDAC.
CONCLUSIONS
Determining tumour subgroups using prognostic factors may be helpful to stratify PDAC patients for future clinical trials. In case of disease recurrence, the site of relapse may have a prognostic impact on subsequent survival. Further investigations are needed to identify differences in tumour biology, reflecting relapse patterns and the differing survival of PDAC patients.
Identifiants
pubmed: 33940349
pii: S0959-8049(21)00203-3
doi: 10.1016/j.ejca.2021.03.036
pii:
doi:
Substances chimiques
Antigens, Tumor-Associated, Carbohydrate
0
Antimetabolites, Antineoplastic
0
carbohydrate antigen 199, human
0
Deoxycytidine
0W860991D6
Gemcitabine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
250-259Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement A.K., J.W., J.S., M.B., S.B., H.R and U.P. declare no conflicts of interest. D.P.M.: Honoraria: Amgen, Roche, Servier, Bristol-Myers Squibb, Pfizer, Taiho Pharmaceutical, Merck Sharp & Dohme. Consulting or Advisory Role: Merck Serono, Amgen, Merck Sharp & Dohme, Roche, Servier, Bristol-Myers Squibb. Research Funding (Institutional): Merck Serono (Inst), Roche (Inst), Amgen (Inst). Travel, Accommodations, Expenses: Amgen, Merck Serono, Bayer HealthCare Pharmaceuticals, Servier, Bristol-Myers Squibb, Roche. H.O.: Honoraria: Servier, Bristol-Myers Squibb. Consulting or Advisory Role: Servier, Bristol-Myers Squibb. Research Funding (Institutional): Bristol-Myers Squibb. Travel, Accommodations, Expenses: Bristol-Myers Squibb. S.K.: Honoraria: Miltenyi Biotec, Fresenius Kabi. Travel, Accommodations, Expenses: Bristol-Myers Squibb, Gilead. M.S.: Honoraria: Sanofi, Astra Zeneca, Leo Pharma, Amgen, Pfizer, Servier, Incyte, MCI, IKF Frankfurt. Consulting or Advisory Role: Merck Serono, Amgen, Merck Sharp & Dohme, Roche, Servier, Bristol-Myers Squibb. Research Funding (Institutional): Leo Pharma, Servier, MSD, Astra Zeneca, Incyte, Boston medical, BMS. Travel, Accommodations, Expenses: Servier.