PARP Inhibitors Show Promise for Hard-to-Treat Breast Cancers

Two new studies reported at this year's ASCO meeting demonstrated the effect of a new class of targeted therapy called poly (ADP-ribose) polymerase (PARP) inhibitors on traditionally difficult-to-treat breast cancers-so-called "triple-negative" breast cancer and BRCA1/2-deficient breast cancers.

BSI-201 for Triple-Negative Breast Cancer
A randomized phase II study, featured in the plenary session at ASCO, showed that women with metastatic triple-negative breast cancer (lacking receptors for estrogen, progesterone, and HER2) who received the investigational poly(ADP-ribose) polymerase (PARP) inhibitor BSI-201, in combination with conventional chemotherapy, lived significantly longer and experienced significantly better progression-free survival than women who received standard chemotherapy alone (abstract P3).

"The results of this study provide early evidence that BSI-201 is a promising treatment for women with triple-negative breast cancer, an aggressive form of the disease for which we need new, more effective therapies," said Joyce O'Shaughnessy, MD, codirector of the Breast Cancer Research Program at Baylor-Charles A. Sammons Cancer Center in Dallas, Texas.

In this study, clinical benefit rate, response rate, progression-free survival, and overall survival were compared among 116 women with metastatic triple-negative breast cancer who were randomly assigned to receive a standard chemotherapy treatment (gemcitabine and carboplatin) plus BSI-201, or standard treatment alone.

Approximately 62% of patients receiving BSI-201 showed clinical benefit, compared with 21% in the chemotherapy-only group. The overall response rate to treatment with the drug combination containing BSI-201 was significantly greater (48%) than in the group receiving only standard chemotherapy (16%). Women who received BSI-201 had a median survival of 9.2 months and median progression-free survival of 6.9 months compared with 5.7 months and 3.3 months, respectively, in women who received standard treatment alone.

Olaparib in BRCA-Deficient Breast Cancer
A small, phase II international multicenter study reported that more than a third of women with BRCA1 or BRCA2 mutations and advanced breast cancer that persisted despite prior treatment experienced tumor shrinkage after receiving the investigational PARP inhibitor olaparib (abstract CRA501).

Lead author Andrew Tutt, MB, ChB, PhD, director of the Breakthrough Breast Cancer Research Unit at Kings College in London, and his colleagues examined the response rate to olaparib in 54 women with breast cancer that was deficient in BRCA1 or BRCA2 and that persisted despite several rounds of standard chemotherapy. About 40% of patients experienced tumor shrinkage at the higher of the two doses used in the study.