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. 2023 Mar;128(5):877-885.
doi: 10.1038/s41416-022-02086-w. Epub 2022 Dec 8.

Second-line therapy in pancreatic ductal adenocarcinoma (PDAC) patients with germline BRCA1-2 pathogenic variants (gBRCA1-2pv)

Giulia Orsi  1   2 , Alessandro Cavaliere  3   4 , Giampaolo Tortora  5   6 , Sara Lonardi  7 , Marina Macchini  1   2 , Mariacristina Di Marco  8   9 , Guido Giordano  10   11 , Enrico Vasile  12 , Mario Scartozzi  13 , Silvia Bozzarelli  14 , Silvia Noventa  15 , Maria Grazia Rodriquenz  16 , Anna Maria Militello  1   2 , Ilario Giovanni Rapposelli  17 , Ingrid Garajova  18 , Stefania De Lorenzo  8   9 , Barbara Merelli  19 , Alessandro Bittoni  14   20 , Lisa Salvatore  5   6 , Letizia Procaccio  21   22 , Chiara Paratore  23 , Andrea Spallanzani  24 , Umberto Peretti  1   2 , Monica Niger  25 , Elisa Giommoni  26 , Ilaria Bernardini  27 , Emiliano Tamburini  28 , Katia Bernardino  29 , Laura Forti  30 , Maria Maddalena Valente  1   2 , Stefano Cascinu  1   2 , Michele Milella #  31 , Michele Reni #  32   33
Affiliations

Second-line therapy in pancreatic ductal adenocarcinoma (PDAC) patients with germline BRCA1-2 pathogenic variants (gBRCA1-2pv)

Giulia Orsi et al. Br J Cancer. 2023 Mar.

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.

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Conflict of interest statement

GT reports advisory board for BMS, AZ, MSD, Merck, Servier. SL reports consulting or advisory role for Amgen, Merck, Serono, Lilly, Astra Zeneca, Incyte, Daiichi-Sankyo, Bristol-Myers Squibb, Servier, MSD; Speakers’ Bureau for Roche, Lilly, Bristol-Myers Squibb, Servier, Merck, Serono, Pierre-Fabre, GSK, Amgen; research funding for Amgen, Merck, Serono, Bayer, Roche, Lilly, Astra Zeneca, Bristol-Myers Squibb. LS reports speakers’ and consultant’s fee from MSD, Astra-Zeneca, Servier, Bayer, Merck, Amgen, Pierre-Fabre. AS reports advisory board or invited speaker for Pierre Fabre, Lilly, Merck, Viatris. MN reports travel expenses from Celgene, speaker honorarium from Accademia della Medicina; honoraria from Medpoint SRL for editorial collaboration; consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte and MSD Italia. SC reports travel expenses and personal honoraria for the following companies: Speaker for Amgen, Bayer, Eli Lilly, Servier; Advisory Boards for Amgen, Eli Lilly, Bayer, Baxter, Merck Sharp & Dohme (MSD), Servier; Consultant for Amgen, Baxter, Eli Lilly, Celgene, Novartis, MSD; Research grant for Celgene, Eisai. MM reports personal honoraria as speaker or consultant for Astrazeneca, MSD, Boehringer Ingelheim, Pfizer, EUSA Pharma, Merck-Serono, Novartis, Roche, Ipsen, Mylan. MR reports advisory boards for Astra-Zeneca, PANAVANCE, Viatris, SOTIO, Servier, MSD, Lilly, Celgene, Shire, Baxter, Sanofi and a research grant from Astra-Zeneca. All remaining authors have declared no competing interests.

Figures

Fig. 1
Fig. 1. Consort flow chart of patients’ selection for the primary analysis.
1LT first-line therapy, PD progressive disease, 2LT second-line therapy.
Fig. 2
Fig. 2. Survival outcome for primary analysis.
Kaplan-Meier curves for progression-free survival2 (a) and overall survival2 (b) of platinum-free versus platinum-based second-line therapy.
Fig. 3
Fig. 3. Survival outcome for secondary analysis.
Kaplan-Meier curves for progression-free survival1 (a) and overall survival (b) of early platinum-containing (triplets/quadruplets and doublets) versus no-early platinum upfront therapy.
See this image and copyright information in PMC

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