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. 2025 Feb;14(3):e70364.
doi: 10.1002/cam4.70364.

Real-World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1-2 Pathogenic Variants

Michele Milella  1   2 , Giulia Orsi  3   4 , Mariacristina di Marco  5   6 , Lisa Salvatore  7   8 , Letizia Procaccio  9 , Silvia Noventa  10 , Silvia Bozzarelli  11 , Ingrid Garajova  12 , Enrico Vasile  13 , Guido Giordano  14   15 , Marina Macchini  3   4 , Alessandro Cavaliere  1 , Marina Gaule  1 , Francesca Bergamo  9 , Marta Chiaravalli  7   8 , Andrea Palloni  6 , Riccardo Carloni  5 , Alessandro Bittoni  16 , Monica Niger  17 , Ilario Giovanni Rapposelli  18 , Maria Grazia Rodriquenz  19 , Mario Scartozzi  20 , Stefania Mosconi  21 , Elisa Giommoni  22 , Ilaria Bernardini  23 , Chiara Paratore  24 , Andrea Spallanzani  25 , Katia Bencardino  26 , Laura Forti  27 , Emiliano Tamburini  28 , Sara Lonardi  9 , Aldo Scarpa  29 , Stefano Cascinu  3   4 , Giampaolo Tortora  7   8 , Isabella Sperduti  30 , Michele Reni  3   4
Affiliations

Real-World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1-2 Pathogenic Variants

Michele Milella et al. Cancer Med. 2025 Feb.

Abstract

Introduction: Pancreatic cancer arising in the context of BRCA predisposition may benefit from poly(ADP-ribose) polymerase inhibitors. We analyzed real-world data on the impact of olaparib on survival in metastatic pancreatic cancer patients harboring germline BRCA mutations in Italy, where olaparib is not reimbursed for this indication.

Methods: Clinico/pathological data of pancreatic cancer patients with documented BRCA1-2 germline pathogenic variants who had received first-line chemotherapy for metastatic disease were collected from 23 Italian oncology departments and the impact of olaparib exposure on overall survival (OS) was analyzed.

Results: Of 114, 53 BRCA-mutant pancreatic cancer patients had received olaparib for metastatic disease. OS was significantly longer in patients who were exposed to olaparib (hazard ratio [HR] 0.568, 95% confidence interval [CI] 0.351-0.918, log-rank p = 0.02) in any setting/line of treatment; similar results were obtained for patients who received olaparib as maintenance treatment (in any line of treatment), patients who had stage IV disease at diagnosis, and patients who did not experience progressive disease as their best response to first-line chemotherapy. Exposure to olaparib in the first-line maintenance setting after platinum-based chemotherapy, however, did not significantly impact survival. At multivariate analysis, CA19.9 levels at diagnosis and response to first-line chemotherapy were independently prognostic; however, when response to chemotherapy was excluded, any exposure to olaparib was a significant independent predictor of longer OS, together with CA19.9 levels.

Conclusion: The real-world data presented here support the use of olaparib for metastatic disease in germline BRCA-mutant pancreatic cancer patients, as it may significantly prolong survival.

Keywords: germline BRCA1/2 pathogenic variants; metastatic; olaparib; pancreatic cancer; poly(ADP‐ribose) polymerase inhibitors; real‐world experience; survival analysis.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michele Milella, Guido Giordano: personal honoraria from AstraZeneca, MSD; travel expenses from AstraZeneca. Giulia Orsi, Silvia Noventa, Silvia Bozzarelli, Ingrid Garajova, Enrico Vasile, Marina Macchini, Alessandro Cavaliere, Marina Gaule, Marta Chiaravalli, Andrea Palloni, Riccardo Carloni, Alessandro Bittoni, Maria Grazia Rodriquenz, Stefania Mosconi, Elisa Giommoni, Ilaria Bernardini, Chiara Paratore, Katia Bencardino, Aldo Scarpa, Stefano Cascinu, Isabella Sperduti: no competing interests. Mariacristina Di Marco: personal honoraria from OncoSil Medical; travel expenses from Viatris. Lisa Salvatore: personal honoraria from MSD, AstraZeneca, Servier, Bayer, Merck, Amgen, Pierre‐Fabre, Takeda, GSK. Letizia Procaccio: participation in advisory boards for AstraZeneca. Francesca Bergamo: participation in advisory boards for Servier, AAA, Novartis; personal honoraria from Eli‐Lilly, MSD, EISAI, Bayer, BMS, Amgen. Monica Niger: personal honoraria from Accademia di Medicina, Incyte, Sandoz, Medpoint SRL, Servier, EMD Serono, Basilea Pharmaceutica, MSD, Astrazeneca, Taiho; travel expenses from AstraZeneca. Ilario Giovanni Rapposelli: participation in Advisory Boards for MSD. Mario Scartozzi: personal honoraria from MSD, GSK, Servier, Astra Zeneca, Astellas, MERCK, Sanofi. Andrea Spallanzani: personal honoraria from Lilly, MSD, Astellas, Astrazeneca, Servier, Pierre Fabre. Laura Forti: participation in advisory boards for Amgen, Merck‐Serono, Servier. Emiliano Tamburini: participation in advisory boards for AstraZeneca, Amgen, Servier, and MSD. Sara Lonardi: research funding (to institution) from Amgen, Astellas, Astra Zeneca, Bayer, Bristol‐Myers Squibb, Daichii Sankyo, Hutchinson, Incyte, Merck Serono, Mirati, MSD, Pfizer, Roche, Servier; personal honoraria from Amgen, Bristol‐Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre‐Fabre, Roche, Servier; participation in advisory boards for Amgen, Astellas, Astra Zeneca, Bayer, Bristol‐Myers Squibb, Daiichi‐Sankyo, GSK, Incyte, Lilly, Merck Serono, MSD, Servier, Takeda. Giampaolo Tortora: participation in advisory boards for AstraZeneca, BMS, MSD, Merck, Servier. Michele Reni: participation in advisory boards for BMS, PANAVANCE, Viatris, SOTIO, Lilly, Servier, MSD, AstraZeneca, Celgene, Shire, Baxter; research funding (to institution) from AstraZeneca.

Figures

FIGURE 1
FIGURE 1
Impact of olaparib exposure on overall survival (OS). (A) Kaplan–Meier curves for OS for the entire population of gBRCA1‐2pv pancreatic ductal adenocarcinoma (PDAC) patients (n = 114), according to having (yes, black line) or not having (no, gray line) received olaparib, are shown; hazard ratio (HR) with 95% confidence interval (CI) and statistical significance of the differences between curves according to log‐rank test are reported. (B) Kaplan–Meier curves comparing gBRCA1‐2pv PDAC patients who received maintenance olaparib in any line of treatment in the absence of progression to the previous line of chemotherapy (yes, black line; n = 43) or did not receive any olaparib (no, gray line; n = 61) are shown; HR with 95% CI and statistical significance of the differences between curves according to log‐rank test are reported.
FIGURE 2
FIGURE 2
Impact of olaparib exposure on overall survival (OS) in subgroups of patients with metastatic disease at diagnosis (M+) or without progressive disease (PD) as best response to first‐line chemotherapy. (A) Kaplan–Meier curves for OS relative to gBRCA1‐2pv pancreatic ductal adenocarcinoma (PDAC) patients with stage IV disease at the time of diagnosis (M+, n = 87), according to having (yes, black line) or not having (no, gray line) received olaparib, are shown; hazard ratio (HR) with 95% confidence interval (CI) and statistical significance of the differences between curves according to log‐rank test are reported. (B) Kaplan–Meier curves for OS relative to gBRCA1‐2pv PDAC patients who did not experience PD as their best response to first‐line chemotherapy (n = 73; of whom, 51 received platinum‐based first‐line chemotherapy), according to having (yes, black line) or not having (no, gray line) received olaparib, are shown; HR with 95% CI and statistical significance of the differences between curves according to log‐rank test are reported.
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