Oncology

Metastatic Pancreatic Cancer

Future of Individualized Treatment With Platinum-Based Chemotherapy

patient care perspectives by Thomas A. Abrams, MD

Overview

Studies of patients with pancreatic cancer have shown that 10% of cases are from an inherited genetic alteration, including the BRCA1 and BRCA2 gene. Platinum-based agents, such as cisplatin, carboplatin, and oxaliplatin, are important targeted therapies for pancreatic cancer patients with BRCA mutations. Several clinical studies have assessed the potential use of BRCA2 mutations as biomarkers and the response of platinum-based chemotherapy. In fact, one large multicenter, case-control retrospective analysis demonstrated a trend toward increased disease-free survival in BRCA-positive patients treated with platinum-based regimens (39.1 months) compared with similarly treated controls (12.4 months). To overcome tumor resistance and improve individualized treatment strategies with platinum-based therapy, structural modification, combination therapy, and improved delivery of platinum drugs are needed. For the subgroup of pancreatic cancer patients with a BRCA mutation, platinum-based therapy is a promising treatment in need of further investigation. A member of our expert panel discusses the future of platinum-based chemotherapy in metastatic pancreatic cancer.

Expert Commentary

Thomas A. Abrams, MD

Assistant Professor of Medicine
Harvard Medical School
Senior Physician
Dana-Farber Cancer Institute
Boston, MA

Although metastatic pancreatic cancer is still a very difficult to treat and lethal disease, we are making positive strides in individual treatment. The research that we are doing is invaluable to continuing our advances. As long as we continue to concentrate on the individual with the disease and try to make his or her life as good as possible, we are doing well for our patients as a whole. The future is certainly bright, and I hope that we will continue to do this work and strive for individual therapy. We definitely tend to look into family history to make a decision regarding front-line platinum agents. Our predilection is to usually give FOLFIRINOX* in the first line for these patients. We have historically given a lot of platinum-based chemotherapy in the first line anyways. It is something we have tended to do, and if a patient’s family history sort of lines up with a BRCA Nef phenotype, then I think we are even more inclined to do so.

“The future is certainly bright, and I hope that we will continue to do this work and strive for individual therapy. We definitely tend to look into family history to make a decision regarding front-line platinum agents.”

Thomas A. Abrams, MD

*FOLFIRINOX: FOL=leucovorin calcium (folinic acid); F=5-fluorouracil; IRIN=irinotecan hydrochloride; OX=oxaliplatin.

References

Basourakos SP, Li L, Aparicio AM, et al. Combination platinum-based and DNA damage response-targeting cancer therapy: evolution and future directions. Curr Med Chem. 2017;24(15):1586-1606.

Chen X, Wu Y, Dong H, et al. Platinum-based agents for individualized cancer treatment. Curr Mol Med. 2013;13(10):1603-1612.

Golan T, Sella T, O’Reilly EM, et al. Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer. Br J Cancer. 2017;116(6):697-702.

Luo G, Lu Y, Jin K, et al. Pancreatic cancer: BRCA mutation and personalized treatment. Expert Rev Anticancer Ther. 2015;15(10):1223-1231.

Martinez-Useros J, Garcia-Foncillas J. The role of BRCA2 mutation status as diagnostic, predictive, and prognosis biomarker for pancreatic cancer. Biomed Res Int. 2016;2016:1869304. doi: 10.1155/2016/1869304.

Pishvaian MJ, Biankin AV, Bailey P, et al. BRCA2 secondary mutation-mediated resistance to platinum and PARP inhibitor-based therapy in pancreatic cancer. Br J Cancer. 2017;116(8):1021-1026.

Teo MY, O’Reilly EM. Is it time to split strategies to treat homologous recombinant deficiency in pancreas cancer? J Gastrointest Oncol. 2016;7(5):738-749.

Verdaguer H, Saurí T, Macarulla T. Predictive and prognostic biomarkers in personalized gastrointestinal cancer treatment. J Gastrointest Oncol. 2017;8(3):405-417.