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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

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Abstract

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.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Author information

Authors and Affiliations

  1. Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20123, Milan, Italy

    Anna Maria Militello, Giulia Orsi, Marina Macchini, Umberto Peretti, Stefano Cascinu & Michele Reni

  2. Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy

    Anna Maria Militello, Giulia Orsi, Marina Macchini, Umberto Peretti, Stefano Cascinu & Michele Reni

  3. Department of Oncology, University of Torino, Candiolo, Italy

    Alessandro Cavaliere

  4. Candiolo Cancer Institute, FPO – IRCCS Candiolo, Candiolo, Italy

    Alessandro Cavaliere

  5. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori Di Milano, Milan, Italy

    Monica Niger

  6. Biologia Cellulare e Bioterapie, Istituto Nazionale per lo Studio e la Cura dei Tumori ‘‘Fondazione Giovanni Pascale’’ - IRCCS, Naples, Italy

    Antonio Avallone

  7. Unit of Medical Oncology, Comprehensive Cancer Center, Fondazione Policlinico Universitario, Agostino Gemelli IRCCS, Rome, Italy

    Lisa Salvatore & Giampaolo Tortora

  8. Università Cattolica del Sacro Cuore, Rome, Italy

    Lisa Salvatore & Giampaolo Tortora

  9. Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) ‘‘Dino Amadori’’, Meldola, Italy

    Ilario Giovanni Rapposelli

  10. Unit of Medical Oncology and Biomolecular Therapy, Policlinico Riuniti, Foggia, Italy

    Guido Giordano

  11. Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy

    Guido Giordano

  12. Department of Medical Oncology, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy

    Silvia Noventa

  13. Medical Oncology Division, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

    Elisa Giommoni

  14. Department of Medical Oncology and Hematology, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, Italy

    Silvia Bozzarelli

  15. Medical Oncology 1 Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy

    Letizia Procaccio

  16. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy

    Letizia Procaccio

  17. University of Genoa, Ospedale Policlinico San Martino IRCCS, Genoa, Italy

    Alberto Puccini

  18. Department of Radiation Oncology and Genomic Instability and Cancer Genetics, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Cristina Montagna

  19. Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy

    Michele Milella

Authors
  1. Anna Maria Militello
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  2. Giulia Orsi
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Correspondence to Michele Reni.

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Conflict of interests

MN reports travel expenses from Celgene and AstraZeneca; speaker honorarium from Accademia della Medicina and Incyte; honoraria from Sandoz, Medpoint SRL and Servier for editorial collaboration; consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte, MSD Italia, Servier and Taiho. AA has served as advisory and speaker for Amgen and Servier. LS reports speakers’ and consultant's fee from MSD, Astra-Zeneca, Servier, Bayer, Merck, Amgen, Pierre-Fabre. GT reports advisory board for BMS, AZ, MSD, Merck, Servier. GG reports honoraria for advisory board from Astra Zeneca. EG reports advisory board for Bristol Myers Squibb, Eli Lilly, Viatris,Amgen, Servier. LP reports personal fee for scientific consultancy from Astra Zeneca. 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 board for BMS, PANAVANCE, Viatris, SOTIO, Lilly, Servier, MSD, Astra-Zeneca, Celgene, Shire, Baxter and a research grant from Astra-Zeneca. All remaining authors have declared no competing interests.

Ethics approval and consent to participate

Before testing, all patients signed an informed consensus statement that was revised and approved by a local ethics committee and allowed for genetic testing and data collection, analysis and elaboration. Data were irreversibly anonymised before entering into the database.

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Militello, A.M., Orsi, G., Cavaliere, A. et al. 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. Cancer Chemother Pharmacol 92, 501–510 (2023). https://doi.org/10.1007/s00280-023-04585-w

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