At the time of her diagnosis with triple-negative breast cancer in March 2017, Vicky Lawrence was living a full life in her hometown of Columbia, Mississippi, dividing her time among teaching high school, singing in her church choir and enjoying her grandchildren.
Her five children urged her to take a break and seek treatment at MD Anderson instead of locally. Lawrence agreed, though she admits it wasn’t her first inclination to venture far from home.
“I said, ‘Oh, that doesn’t even make sense for me to travel all that way, to go that far. And besides, the time involved and having someone to travel with me …’ “And my kids, they said, ‘Mama, we’ll make sure it happens.’”
With her children’s support, Lawrence committed to treatment at MD Anderson, where she qualified for a clinical trial led by Jennifer Litton, M.D., associate professor of Breast Medical Oncology. The clinical trial allowed Lawrence, who’d tested positive for the BRCA genetic mutation that’s linked to breast cancer, to take daily oral medication as a first-line treatment. Chemotherapy followed by surgery is considered the front-line therapy for many BRCA-related cancers.
The size of Lawrence’s tumor, along with her BRCA mutation, made her eligible for Litton’s trial testing a PARP inhibitor drug named talazoparib. PARP inhibitors work by blocking a protein known as PARP that fixes damaged DNA inside cells. Blocking PARP’s repair action may help prevent cancer cells from repairing their damaged DNA, causing them to die.
Talazoparib had produced remarkable results in a small pilot study previously conducted by Litton for patients with early-stage breast cancer and BRCA 1 and 2 mutations. The drug shrank tumors in all 13 patients enrolled in the pilot study, anywhere from 30 to 98 percent, with a median reduction of 88 percent. Some tumors disappeared completely.
Encouraged by the results, Lawrence enrolled in Litton’s extension trial of talazoparib that followed the initial pilot study. Over the next six months, she took talazoparib once daily, followed by ultrasounds every two months to check on the status of the tumor in her left breast.
“Every time, my tumor had reduced significantly. That was very encouraging to see,” she says. “At the end, when I had my double mastectomy, the report was that there were zero cancer cells left in my breast tissue.”
Throughout her breast cancer treatment, Lawrence says she felt few side effects, and was able to continue life at a normal pace.
“The treatments didn’t prevent me from working. Instead, I went on with my everyday life. I sang in the choir, went to Daughters of the American Revolution chapter meetings, and played with my grandbabies,” she says. “It just didn’t slow me down.”
Litton shared the results of the extension trial at the 2018 American Society of Clinical Oncology Annual Meeting in June. The study found that more than half of the 20 women in the study who took the drug once daily prior to surgery had no evidence of disease at the time of surgery.
“It was the first trial of its kind showing that a single, targeted therapy was able to eradicate the tumor in the breast by the time of surgery,” Litton says.
Based on the clinical trial’s success, a larger, Phase II, single-arm trial of talazoparib with a similar design is now open and recruiting patients. Litton is the principal investigator.
PARP inhibitors also have shown promise as a treatment for metastatic breast cancer. Litton’s recently concluded EMBRACA study found that talazoparib extended progression-free survival and improved quality-of-life measures over chemotherapy for patients with metastatic breast cancer and BRCA mutations. The clinical trial paved the way for the Food and Drug Administration’s approval of the drug for metastatic breast cancer in October.
“If we can better identify a group of people who benefit from this medication and avoid chemotherapy when it’s not necessary and get the same outcomes, that would certainly be helpful for the patient,” Litton says.