Treatment of pancreatic cancer metastasized to the liver – A case study

In the fall of 2015, 44-year-old Doron Broman was diagnosed with pancreatic cancer and was surprised to find that it had metastasized to a large tumor on the liver. Faced with a survival period of only a few months, Broman decided to spend his limited time in the right place. A Miami-based real estate developer with a home in Boston, he conducted research online and decided to receive treatment at Dana-Farber. His doctor, Kimmie Ng, MD, MPH, director of clinical research at the Gastrointestinal Cancer Treatment Center, recommended the FOLFIRINOX regimen — the strongest combination chemotherapy available for pancreatic cancer.

Broman flew from Miami to Boston every two weeks for treatment. To everyone's surprise, the malignancies of his pancreas and liver began to shrink rapidly. Several tumors almost completely disappeared after chemotherapy, leading his oncologist to wonder whether a molecular mutation in his tumor was making it particularly sensitive to FOLFIRINOX. These types of patients, who respond significantly better than expected to a drug, are called "special responders," and in the era of precision medicine, sequencing their tumor DNA may identify rare mutations that explain their exceptional response.

Broman arrived at Dana-Farber just as Ng and her colleagues had started a new research protocol allowing patients to undergo additional biopsies for precision medicine analysis. After agreeing to participate, the entire exon sequence of his tumor DNA revealed mutations in the BRCA2 gene. Unlike inherited BRCA2 mutations that increase the risk of breast and ovarian cancer in women, Broman's mutation was not inherited — at some point in his life, his pancreatic cells had randomly acquired it.

BRCA2 mutations can interfere with a cell's ability to repair DNA damage, causing the cell to destroy itself. Cancer cells with this mutation are particularly sensitive to platinum-based chemotherapeutic drugs that work through DNA damage, which is part of the FOLFIRINOX protocol — likely explaining why Broman's cancer responded so dramatically. After 13 cycles of FOLFIRINOX, his medical team decided to transition him to a targeted drug called olaparib (Lynparza), a PARP inhibitor that further hinders DNA damage repair. Though olaparib is approved for hereditary BRCA2-related ovarian cancer, its role in somatic (non-hereditary) BRCA2-mutated tumors was still being explored.

Broman stopped FOLFIRINOX and began taking olaparib daily, reporting no significant side effects. Six months into his new protocol, MRI and CT scans showed no cancer recurrence, and his pancreatic cancer blood biomarker levels remained within normal limits. His oncologist's plan was to keep him on olaparib indefinitely, as long as it continued to control the cancer with minimal side effects.

Broman shared: "I am really happy. I've done much better than I expected. I feel good, my hair is back, I'm healthy, I walk 12 miles a day. My friends said they couldn't believe it." For Ng and her colleagues, Broman's case powerfully demonstrates that precision oncology and targeted therapy based on a tumor's molecular characteristics can offer tremendous benefit to cancer patients — opening a new chapter in how metastatic pancreatic cancer can be approached and treated.