Clinical outcomes and response to chemotherapy in a cohort of pancreatic cancer patients with germline variants of unknown significance (VUS) in BRCA1 and BRCA2 genes.

Autor: Militello AM; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20123, Milan, Italy.; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy., Orsi G; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20123, Milan, Italy.; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy., Cavaliere A; Department of Oncology, University of Torino, Candiolo, Italy.; Candiolo Cancer Institute, FPO - IRCCS Candiolo, Candiolo, Italy., Niger M; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori Di Milano, Milan, Italy., Avallone A; Biologia Cellulare e Bioterapie, Istituto Nazionale per lo Studio e la Cura dei Tumori ''Fondazione Giovanni Pascale'' - IRCCS, Naples, Italy., Salvatore L; Unit of Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario, Agostino Gemelli IRCCS, Rome, Italy.; Università Cattolica del Sacro Cuore, Rome, Italy., Tortora G; Unit of Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario, Agostino Gemelli IRCCS, Rome, Italy.; Università Cattolica del Sacro Cuore, Rome, Italy., Rapposelli IG; Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) ''Dino Amadori'', Meldola, Italy., Giordano G; Unit of Medical Oncology and Biomolecular Therapy, Policlinico Riuniti, Foggia, Italy.; Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy., Noventa S; Department of Medical Oncology, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy., Giommoni E; Medical Oncology Division, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy., Bozzarelli S; Department of Medical Oncology and Hematology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, Italy., Macchini M; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20123, Milan, Italy.; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy., Peretti U; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20123, Milan, Italy.; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy., Procaccio L; Medical Oncology 1 Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy., Puccini A; University of Genoa, Ospedale Policlinico San Martino IRCCS, Genoa, Italy., Cascinu S; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20123, Milan, Italy.; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy., Montagna C; Department of Radiation Oncology and Genomic Instability and Cancer Genetics, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA., Milella M; Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy., Reni M; Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20123, Milan, Italy. reni.michele@hsr.it.; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. reni.michele@hsr.it.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2023 Dec; Vol. 92 (6), pp. 501-510. Date of Electronic Publication: 2023 Sep 19.
DOI: 10.1007/s00280-023-04585-w
Abstrakt: Purpose: The clinical outcome and the efficacy of chemotherapy in pancreatic cancer patients with BRCA1/2 Variants of Unknown Significance (VUS) is unknown. We explored the effects of chemotherapy with or without Platinum in non metastatic and metastatic pancreatic cancer patients with BRCA1/2 VUS.
Methods: A retrospective analysis of non-metastatic or metastatic pancreatic cancer patients with gBRCA1/2 VUS treated in 13 Italian centers between November 2015 and December 2020 was performed. All patients were assessed for toxicity and RECIST 1.1 response. Metastatic patients were evaluated for survival outcome.
Results: 30 pancreatic cancer patients with gBRCA1/2 VUS were considered: 20 were M+ and 10 were non-M+. Pl-CT was recommended to 16 patients: 10 M+ (6 FOLFIRINOX and 4 PAXG) and 6 non-M+ (3 FOLFIRINOX and 3 PAXG); 11 patients received Nabpaclitaxel-Gemcitabine (AG; 8 M+) and 3 patients (2 M+) were treated with Gemcitabine (G). The RECIST 1.1 response rate was 27% for AG and 44% for Pl-CT (22% for (m) FOLFIRINOX and 71% PAXG). 1 year Progression-Free Survival was 37.5% for patients treated with AG and 33% in the Pl-CT subgroup. Median Overall Survival (OS) was 23.5 months for patients treated with AG and 14 months for the Pl-CT subgroup. 1 Year and 2 Year OS were numerically better for AG (1 Year OS: 75% vs 60% and 2 Year OS: 50% and 20% in AG and Pl-CT subgroups, respectively) as well.
Conclusions: Pl-CT does not seem to be associated with a better outcome compared to AG chemotherapy in PDAC patients with BRCA 1/2 VUS.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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