Real‐World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1‐2 Pathogenic Variants
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...
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2025-02-01
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| Online Access: | https://doi.org/10.1002/cam4.70364 |
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| author | Michele Milella Giulia Orsi Mariacristina diMarco Lisa Salvatore Letizia Procaccio Silvia Noventa Silvia Bozzarelli Ingrid Garajova Enrico Vasile Guido Giordano Marina Macchini Alessandro Cavaliere Marina Gaule Francesca Bergamo Marta Chiaravalli Andrea Palloni Riccardo Carloni Alessandro Bittoni Monica Niger Ilario Giovanni Rapposelli Maria Grazia Rodriquenz Mario Scartozzi Stefania Mosconi Elisa Giommoni Ilaria Bernardini Chiara Paratore Andrea Spallanzani Katia Bencardino Laura Forti Emiliano Tamburini Sara Lonardi Aldo Scarpa Stefano Cascinu Giampaolo Tortora Isabella Sperduti Michele Reni |
| author_facet | Michele Milella Giulia Orsi Mariacristina diMarco Lisa Salvatore Letizia Procaccio Silvia Noventa Silvia Bozzarelli Ingrid Garajova Enrico Vasile Guido Giordano Marina Macchini Alessandro Cavaliere Marina Gaule Francesca Bergamo Marta Chiaravalli Andrea Palloni Riccardo Carloni Alessandro Bittoni Monica Niger Ilario Giovanni Rapposelli Maria Grazia Rodriquenz Mario Scartozzi Stefania Mosconi Elisa Giommoni Ilaria Bernardini Chiara Paratore Andrea Spallanzani Katia Bencardino Laura Forti Emiliano Tamburini Sara Lonardi Aldo Scarpa Stefano Cascinu Giampaolo Tortora Isabella Sperduti Michele Reni |
| author_sort | Michele Milella |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7ac904c520084aefb665f33f55d22688 |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-7ac904c520084aefb665f33f55d226882025-08-20T02:22:09ZengWileyCancer Medicine2045-76342025-02-01143n/an/a10.1002/cam4.70364Real‐World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1‐2 Pathogenic VariantsMichele Milella0Giulia Orsi1Mariacristina diMarco2Lisa Salvatore3Letizia Procaccio4Silvia Noventa5Silvia Bozzarelli6Ingrid Garajova7Enrico Vasile8Guido Giordano9Marina Macchini10Alessandro Cavaliere11Marina Gaule12Francesca Bergamo13Marta Chiaravalli14Andrea Palloni15Riccardo Carloni16Alessandro Bittoni17Monica Niger18Ilario Giovanni Rapposelli19Maria Grazia Rodriquenz20Mario Scartozzi21Stefania Mosconi22Elisa Giommoni23Ilaria Bernardini24Chiara Paratore25Andrea Spallanzani26Katia Bencardino27Laura Forti28Emiliano Tamburini29Sara Lonardi30Aldo Scarpa31Stefano Cascinu32Giampaolo Tortora33Isabella Sperduti34Michele Reni35Department of Engineering for Innovation Medicine (DIMI), Specialty School in Medical Oncology and Section of Innovation Biomedicine—Oncology Area Faculty of Medicine and Surgery, University of Verona Verona ItalyDepartment of Medical Oncology IRCCS Ospedale San Raffaele Milan ItalyDepartment of Medical and Surgical Sciences Alma Mater Studiorum University of Bologna Bologna ItalyMedical Oncology Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia Rome ItalyDepartment of Oncology Veneto Institute of Oncology IRCCS Padova ItalyMedical Oncology Fondazione Poliambulanza Istituto Ospedaliero Brescia ItalyIRCCS Humanitas Research Hospital Milan ItalyMedical Oncology Unit University Hospital of Parma Parma ItalyUnit Medical Oncology Azienda Ospedaliero‐Universitaria Pisana, Oncology Pisa ItalyPoliclinico Riuniti di Foggia Unit of Medical Oncology and Biomolecular Therapy Foggia ItalyDepartment of Medical Oncology IRCCS Ospedale San Raffaele Milan ItalyDepartment of Engineering for Innovation Medicine (DIMI), Specialty School in Medical Oncology and Section of Innovation Biomedicine—Oncology Area Faculty of Medicine and Surgery, University of Verona Verona ItalyDepartment of Engineering for Innovation Medicine (DIMI), Specialty School in Medical Oncology and Section of Innovation Biomedicine—Oncology Area Faculty of Medicine and Surgery, University of Verona Verona ItalyDepartment of Oncology Veneto Institute of Oncology IRCCS Padova ItalyMedical Oncology Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia Rome ItalyMedical Oncology Unit IRCSS Azienda Ospedaliero Universitaria di Bologna Bologna ItalyDepartment of Medical and Surgical Sciences Alma Mater Studiorum University of Bologna Bologna ItalyOncology Unit Azienda Ospedaliero‐Universitaria Ospedali Riuniti Umberto I—GM Lancisi—G Salesi di Ancona Ancona ItalyMedical Oncology Department Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano Milan ItalyDepartment of Medical Oncology IRCCS Istituto Romagnolo per Lo Studio Dei Tumori “Dino Amadori”—IRST Meldola ItalyOncology Unit Ospedale IRCCS Casa Sollievo Della Sofferenza San Giovanni Rotondo (FG) ItalyMedical Oncology University and University Hospital Cagliari ItalyOncology Unit ASST Papa Giovanni XIII Bergamo ItalyMedical Oncology Division Azienda Ospedaliero‐Universitaria Careggi Firenze ItalyMedical Oncology Unit Ospedale Ramazzini Carpi (MO) ItalyDepartment of Oncology University of Turin, Ordine Mauriziano Hospital Turin ItalyDepartment of Oncology and Hematology University Hospital of Modena Modena ItalyNiguarda Cancer Center Grande Ospedale Metropolitano Niguarda Milan ItalyMedical Oncology Division Azienda Ospedaliero‐Universitaria Maggiore Della Carità Novara ItalyMedical Oncology and Palliative Care Department Azienda Ospedaliera Cardinale G. Panico Lecce ItalyDepartment of Oncology Veneto Institute of Oncology IRCCS Padova ItalyARC‐Net Research Centre and Department of Diagnostics and Public Health—Section of Pathology University of Verona Verona ItalyDepartment of Medical Oncology IRCCS Ospedale San Raffaele Milan ItalyMedical Oncology Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia Rome ItalyClinical Trial Center—Biostatistics & Bioinformatics IRCCS—Regina Elena National Cancer Institute Rome ItalyDepartment of Medical Oncology IRCCS Ospedale San Raffaele Milan ItalyABSTRACT 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.https://doi.org/10.1002/cam4.70364germline BRCA1/2 pathogenic variantsmetastaticolaparibpancreatic cancerpoly(ADP‐ribose) polymerase inhibitorsreal‐world experience |
| spellingShingle | Michele Milella Giulia Orsi Mariacristina diMarco Lisa Salvatore Letizia Procaccio Silvia Noventa Silvia Bozzarelli Ingrid Garajova Enrico Vasile Guido Giordano Marina Macchini Alessandro Cavaliere Marina Gaule Francesca Bergamo Marta Chiaravalli Andrea Palloni Riccardo Carloni Alessandro Bittoni Monica Niger Ilario Giovanni Rapposelli Maria Grazia Rodriquenz Mario Scartozzi Stefania Mosconi Elisa Giommoni Ilaria Bernardini Chiara Paratore Andrea Spallanzani Katia Bencardino Laura Forti Emiliano Tamburini Sara Lonardi Aldo Scarpa Stefano Cascinu Giampaolo Tortora Isabella Sperduti Michele Reni Real‐World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1‐2 Pathogenic Variants Cancer Medicine germline BRCA1/2 pathogenic variants metastatic olaparib pancreatic cancer poly(ADP‐ribose) polymerase inhibitors real‐world experience |
| title | Real‐World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1‐2 Pathogenic Variants |
| title_full | Real‐World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1‐2 Pathogenic Variants |
| title_fullStr | Real‐World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1‐2 Pathogenic Variants |
| title_full_unstemmed | Real‐World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1‐2 Pathogenic Variants |
| title_short | Real‐World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1‐2 Pathogenic Variants |
| title_sort | real world impact of olaparib exposure in advanced pancreatic cancer patients harboring germline brca1 2 pathogenic variants |
| topic | germline BRCA1/2 pathogenic variants metastatic olaparib pancreatic cancer poly(ADP‐ribose) polymerase inhibitors real‐world experience |
| url | https://doi.org/10.1002/cam4.70364 |
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