학술논문
Second-line therapy in pancreatic ductal adenocarcinoma (PDAC) patients with germline BRCA1-2 pathogenic variants (gBRCA1-2pv).
Document Type
Article
Author
Orsi, Giulia; Cavaliere, Alessandro; Tortora, Giampaolo; Lonardi, Sara; Macchini, Marina; Di Marco, Mariacristina; Giordano, Guido; Vasile, Enrico; Scartozzi, Mario; Bozzarelli, Silvia; Noventa, Silvia; Rodriquenz, Maria Grazia; Militello, Anna Maria; Rapposelli, Ilario Giovanni; Garajova, Ingrid; De Lorenzo, Stefania; Merelli, Barbara; Bittoni, Alessandro; Salvatore, Lisa; Procaccio, Letizia
Source
Subject
Language
ISSN
0007-0920
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) harbouring germline BRCA1-2 pathogenic variants (gBRCA1-2pv) is a distinct nosological entity. Information on second-line therapy (2LT) outcome in this setting is lacking. Methods: Data of gBRCA1-2pv metastatic PDAC patients treated with chemotherapy were collected. A primary analysis of 2LT RECIST response, median progression-free survival (mPFS2) and overall survival (mOS2), was performed. A secondary analysis addressed the impact of timing of platinum introduction on the outcome of patients receiving at least a first-line combination chemotherapy (1LT). Results: Eighty-four gBRCA1-2pv metastatic PDAC patients were enrolled. The primary analysis, including 43 patients, highlighted a significant improvement of mPFS2 and a doubled response rate, in the platinum-based 2LT subgroup as compared to the platinum-free (8.8 versus 3.7 months, p = 0.013). Seventy-seven patients were included in the secondary analysis. Median PFS1 of 3- and 4-drug platinum-based 1LT significantly outperformed both platinum-free combinations and platinum-based doublets (11.4 versus 6.4 versus 7.9 months, p = 0.01). Albeit still immature, data on mOS paralleled those on mPFS. Conclusions: This study highlighted the beneficial role of platinum agents in gBRCA1-2pv PDAC patients also in second-line treatment setting. However, our data suggest that early use of 3- and 4-drug platinum-based chemotherapy combinations provides a survival outcome advantage. [ABSTRACT FROM AUTHOR]