Veliparib Improved Response to Chemotherapy Without Boosting Survival

Veliparib Improved Response to Chemotherapy Without Boosting Survival

Adding the experimental PARP inhibitor veliparib to chemotherapy increased the number of patients who responded to treatment without worsening side effects, but failed to lengthen progression-free survival times, a breast cancer Phase 2 clinical trial (NCT01506609) has shown.

The findings were reported at the 2016 San Antonio Breast Cancer Symposium last week.

Although the addition of veliparib failed to lengthen patients’ lives, researchers hope to see longer survival times in the Phase 3 BROCADE 3 (NCT02163694) trial that is under way. They said the Phase 2 trial’s enrollment of 290 patients may have been too small to show a difference in survival. More people are involved in Phase 3.

PARP (poly(ADP-ribose) polymerase) is a protein that repairs DNA damage in cells. The researchers hope that in blocking the DNA repair system, veliparib will increase the chance that cancer cells die during chemotherapy.

The Phase 2 clinical trial  recruited metastatic breast cancer patients whose cancer had recurred after treatment. The women had mutations in their BRCA1 or BRCA2 genes. Such mutations increase the risk of cancer but also make cancer cells more sensitive to therapies that destroy their DNA.

“Preclinical studies have shown that blocking a second DNA repair pathway in BRCA-mutant cancer cells using a PARP inhibitor makes the cells more susceptible to the effects of chemotherapeutics such as carboplatin,” Heather S. Han, MD, an associate member of the Moffitt Cancer Center in Tampa, Florida, said in a press release.

The trial involved the 290 patients receiving either veliparib or a placebo, in combination with the chemotherapy drugs Paraplatin (carboplatin) or Taxol (paclitaxel). A third group received veliparib together with temozolomide, whose brand name is Temodar in the US and Temodal in Europe. The third-group findings were not presented at the meeting.

More than half the patients in the first two groups had tumors connected with an estrogen receptor, about 40 percent had triple-negative breast cancer, and a few had tumors positive for HER2. Patients with different tumor characteristics were equally divided between the treatment groups receiving veliparib and either Paraplatin or Taxol.

The results were that 77.8 percent in the group receiving veliparib responded to the treatment, compared with 61.3 percent in the placebo group. Progression-free survival was 14.1 months among veliparib-treated patients and 12.3 months in the placebo group — a difference that was not statistically significant. A small improvement in the over-all survival rate, from 25.9 to 28.3 months, also was not statistically significant.

Veliparib did not worsen the side effects associated with chemotherapy. The most common problem was a reduction in immune cells called neutrophils, which occurred in 56% percent of the veliparib group and 55% of the placebo groups. Low numbers of blood platelets were seen in 31% of the veliparib group and in 26% of the placebo group.

 

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