ASCO 2014: Experimental drug has potential for BRCA-linked breast cancer

May 26, 2014 | by Hiu Chung So

For patients with BRCA mutation-associated breast cancer, the experimental drug ABT-888 — also known as veliparib — is showing promise as a treatment, according to phase II clinical trial results that will be reported at the upcoming annual meeting of the American Society of Clinical Oncology.

PARP1 enzyme An experimental drug may be effective against BRCA-associated breast cancers by inhibiting PARP enzymes, such as PARP1 modeled above, which help cancer cells survive DNA-damaging treatments.

The study abstract will be presented on June 1 by the study's first author, George Somlo, M.D., professor of breast oncology at City of Hope's Department of Medical Oncology & Therapeutics Research.

"Normal cells use an enzyme called PolyADP ribose polymerases (PARP) to repair DNA damage, but cancer cells can exploit PARP to resist DNA-damaging radiation and chemotherapy," explained Somlo. "Because veliparib works by blocking this protein, we wanted to see whether it has any benefit against breast cancer."

Somlo and Jeffrey Weitzel, M.D., director of City of Hope's Division of Clinical Cancer Genetics, focused on BRCA-related breast cancer because the associated genes also code for DNA repair proteins. BRCA gene dysfunctions already compromise the cancer's ability to self-repair, so an additional knockout of PARP enzymes may induce cancer cells to self-destruct or render them especially susceptible to DNA-damaging therapies.

For this clinical trial, Somlo and his colleagues treated 41 patients, all with metastatic breast cancer and carrying a BRCA1 or BRCA2 gene mutation, with 400 milligrams of veliparib twice a day. Upon detectable progression of the disease, the patients were then switched to a combination regimen of 150 milligrams of veliparib twice a day plus an intravenous infusion of carboplatin, a DNA-damaging drug that is also being studied for its efficacy against breast cancer.

After more than 10 months of treatment and monitoring, 20 patients remain on veliparib-only therapy — indicating their disease has not progressed — and another 10 proceeded onto veliparib and carboplatin therapy. (It was too early to assess treatment of three patients at the time of this abstract’s publication.)

Somlo and his team also reported that partial responses were seen in both veliparib-only and veliparib+carboplatin groups.

Given these findings, the researchers concluded that further trials are warranted to investigate the drug’s potential benefits against BRCA-associated breast cancer.


Learn more about breast cancer treatment and research at City of Hope.

The abstract (#1021) is available ahead of the meeting on ASCO's website.



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