Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation
-
Published:2019-12-02
Issue:3
Volume:122
Page:333-339
-
ISSN:0007-0920
-
Container-title:British Journal of Cancer
-
language:en
-
Short-container-title:Br J Cancer
Author:
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.
Abstract
Abstract
Background
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.
Methods
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.
Results
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).
Conclusion
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.
Funder
Basser Young Leadership Council of the Basser Center for BRCA
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
Reference31 articles.
1. Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M. & Matrisian, L. M. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74, 2913–2921 (2014). 2. Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2013. CA 63, 11–30 (2013). 3. Burris, H. A. 3rd, Moore, M. J., Andersen, J., Green, M. R., Rothenberg, M. L., Modiano, M. R. et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol. 15, 2403–2413 (1997). 4. Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 357, 409–413 (2017). 5. Holter, S., Borgida, A., Dodd, A., Grant, R., Semotiuk, K., Hedley, D. et al. Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma. J. Clin. Oncol. 33, 3124–3129 (2015).
Cited by
127 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|