Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation

Retrospective studies suggest a survival benefit when platinum-based chemotherapy is administered to patients with pancreatic cancer harbouring a germline mutation in BRCA1, BRCA2 or PALB2 (mut-positive PDAC). However, the objective response rate (ORR) and real-world progression free survival (rwPFS...

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Bibliographic Details
Published in:British journal of cancer 2020-02, Vol.122 (3), p.333-339
Main Authors: Wattenberg, Max M, Asch, Daniella, Yu, Shun, O'Dwyer, Peter J, Domchek, Susan M, Nathanson, Katherine L, Rosen, Mark A, Beatty, Gregory L, Siegelman, Evan S, Reiss, Kim A
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adult
Aged
Aged, 80 and over
Albumins - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
BRCA1 protein
BRCA1 Protein - genetics
BRCA2 protein
BRCA2 Protein - genetics
Carcinoma, Pancreatic Ductal - drug therapy
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - pathology
Case-Control Studies
Chemotherapy
Cisplatin - administration & dosage
Deoxycytidine - administration & dosage
Deoxycytidine - analogs & derivatives
Fanconi Anemia Complementation Group N Protein - genetics
Female
Fluorouracil - therapeutic use
Gemcitabine
Germ-Line Mutation
Humans
Irinotecan - therapeutic use
Leucovorin - therapeutic use
Liver Neoplasms - drug therapy
Liver Neoplasms - secondary
Lung Neoplasms - drug therapy
Lung Neoplasms - secondary
Lymphatic Metastasis
Male
Middle Aged
Mutation
Organoplatinum Compounds - therapeutic use
Oxaliplatin - therapeutic use
Paclitaxel - administration & dosage
Pancreatic cancer
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - pathology
Patients
Platinum
Prognosis
Progression-Free Survival
Retrospective Studies
Survival
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Summary:Retrospective studies suggest a survival benefit when platinum-based chemotherapy is administered to patients with pancreatic cancer harbouring a germline mutation in BRCA1, BRCA2 or PALB2 (mut-positive PDAC). However, the objective response rate (ORR) and real-world progression free survival (rwPFS) achieved with such treatment remain ill-defined. Twenty-six patients with advanced-stage mut-positive PDAC who had been treated with platinum-based therapy were matched by age, race and sex to 52 platinum-treated control PDAC patients. Responses to therapy were determined by RECIST v1.1, performed by blinded radiology review. Measured outcomes included ORR and rwPFS. The ORR in mut-positive patients was 58% compared to 21% in the control group (p = 0.0022). There was no significant difference in ORR between platinum regimens in mut-positive patients (p = 0.814), whereas in control patients, the only observed responses were to FOLFIRINOX. rwPFS was 10.1 mo. for mut-positive patients and 6.9 mo. for controls (HR 0.43; 95% CI 0.25-0.74; 0.0068). Mut-positive PDAC has a high ORR and prolonged rwPFS to platinum-based chemotherapy. These findings may have implications particularly in the neoadjuvant setting, and for future clinical trial design, and highlight the importance of early germline testing in patients with PDAC.
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-019-0582-7