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Multicenter Study
. 2024 Nov:212:115051.
doi: 10.1016/j.ejca.2024.115051. Epub 2024 Oct 1.

Olaparib as maintenance therapy in non resectable pancreatic adenocarcinoma associated with homologous recombination deficiency profile: A French retrospective multicentric AGEO real-world study

Jeannie M'Baloula  1 , David Tougeron  2 , Alice Boilève  3 , Elodie Jeanbert  4 , Rosine Guimbaud  5 , Meher Ben Abdelghani  6 , Alice Durand  7 , Anthony Turpin  8 , Stanislas Quesada  9 , Jean Frédéric Blanc  10 , Pascal Artru  11 , Clémence Toullec  12 , Isabelle Trouilloud  13 , Anna Pellat  14 , Yann Touchefeu  15 , Julien Pinot  16 , François-Xavier Caroli-Bosc  17 , Julien Taïeb  18 , Solène Doat  19 , Olivier Bouché  20 , Anne Laure Védie  21 , Louis de Mestier  21 , Marie Muller  22
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Free article
Multicenter Study

Olaparib as maintenance therapy in non resectable pancreatic adenocarcinoma associated with homologous recombination deficiency profile: A French retrospective multicentric AGEO real-world study

Jeannie M'Baloula et al. Eur J Cancer. 2024 Nov.
Free article

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. The POLO trial showed that olaparib (PARP inhibitor) improved progression-free survival (PFS) but not overall survival (OS), when used as maintenance therapy after ≥ 16 weeks of disease control with first-line platinum-based chemotherapy in patients with germline (g) BRCA 1 or 2 pathogenic variants (PV) metastatic PDAC. However, real-world data on the effectiveness of olaparib are missing.

Methods: Patients with unresectable PDAC associated with somatic (s) or (g)BRCA1/2 and (g)non-BRCA-HRD PV (i.e. other homologous recombination deficiency/HRD genes) who were treated with olaparib between 2020-2023 were included. The primary objective was to describe treatment patterns. Secondary exploratory objectives included OS and PFS in patients treated with olaparib according to the POLO trial or not, OS and PFS in patients with (g)HRD PV-associated PDAC versus (s)PVs, olaparib safety profile and factors associated with olaparib poor outcomes.

Results: Among 85 patients, 45.9 % received olaparib as defined by the POLO trial. No difference in OS and PFS was observed between patients who received olaparib according to the POLO trial versus not. Patients with (g)HRD PV-associated PDAC had better OS compared to others (22.3 versus 10.5 months, p = 0.038). Factors associated with olaparib poor outcomes included a high neutrophil-to-lymphocyte ratio and the use of olaparib outside the recommendations of the POLO trial. Few grade ≥ 3 adverse events were reported (9.4 %).

Conclusion: Patients with (g)HRD PV-associated PDAC had longer OS than those with (s)HRD PV. Olaparib use beyond the scope of the POLO trial was associated with poor outcomes.

Keywords: (MeSH terms); BRCA; Hereditary neoplastic syndromes; Homologous recombination deficiency; PARP inhibitor; Pancreatic ductal adenocarcinoma.

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Conflict of interest statement

Declaration of Competing Interest APe declares speaker’s engagement from Servier; consulting/advisory role for Amgen; travel grant from Ipsen, Merk and Servier. DT reports consultancy, advisory fees, honoraria from Servier, Pierre Fabre, Merck Serono, MSD, BMS, AZ, Roche, Sanofi; research funding from Sandoz, Astra Zenenca, Servier, MSD; travel grants from Pierre Fabre, MSD, Servier, Roche. JT has received honoraria as a speaker and/or in an advisory role from: AMGEN, Astellas, Astra Zeneca, BMS, Boehringer Ingelheim, Merck KGaA, MSD, Novartis, ONO pharmaceuticals, Pierre Fabre, Roche Genentech, Sanofi, Servier, Takeda. MM reports consultancy, advisory fees, honoraria from Pierre Fabre, Merck Serono, MSD, Takeda; travel grants from Pierre Fabre, Servier. OB reports consultancy, advisory fees, honoraria from Servier, Amgen, Pierre Fabre, Merck Serono, MSD, Takeda, Deciphera; travel grants from Pierre Fabre, Servier, MSD.

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